中国记忆门诊指南：阿尔茨海默病全面纵向治疗计划

Preface

Dementia is the progressive loss of cognitive and physical functions, which affects the memory, orientation, visual and spatial sense, decision-making and ability to communicate and express own desires. In China, since the system of social services has not been established yet, the non-drug treatment is particularly important in the care of patients. An excellent memory clinic / center plays a vital role in supporting families and caregivers. The longitudinal patient support program should include prescription drug therapy and non-drug part of medical care support, such as lifestyle and economical /legal issues, as shown in Figure 4.

The medical cares of specialists can help implement interventions on risk factors in high-risk older adults and delay in occurrence of diseases; and delay the disease progression, improve cognition and enhance quality of life for onset patients. Facing against the backdrop of rapid aging, medical care staff, pharmaceutical staff, government and media and social scholars are striving to achieve this goal. We have established the memory clinic, which could not only provide approved effective drugs to guide rational medication for a long term, but also comprehensive, diverse non-drug therapy. When the disease progression to advanced dementia, the elderly patients may not consent to treatment, to participate in study or participate in the decision-making of care, and their daily life may be affected, for example, making a will or dealing with his/her property. In almost all countries, specialists play an important role, including evaluation on mental abilities which may be performed prior to the treatment, showing the medical certificate upon request of a lawyer including the special work irrelevant to medical services, supporting legal documents, or proving suggestions related to court’ s trial. The physician can provide information to evaluate the ability of patients. On the basis of physician’s evaluation, the law enforcement official can make a correct decision and judgment. Specialists who take care of patients with dementia should be familiar with the national legislation related to ability evaluation, informed consent of treatment and study, diagnosis disclosure and prior instructions (living will) [1]. 

The changed functional and structural characteristics of human brain (neural plasticity) enable people to adapt to the changing needs. With the plasticity, we can study and acquire new skills [2].  Recent research indicates that, neural plasticity can happen in the aging brain to a great extent. The cognitive training is useful process, which is conducive to building compensation neural circuits and recovering the functions lost [3]. Studies have shown that, with the aging, the perceptual - cognitive changes may also happen in healthy persons [4]. The training can improve the cognitive / perceptual – cognitive functions of older adults. Studies reported that the cognitive training can be transferred to the social-related tasks. The cognitive training process using a specific program can not only implement the task itself, but also enhance the social-related functions [5], for example, through ordinary memory training, the memory on social-related information is improved, such as memory on household activities, telephone number, etc.. The animal tests have showed that, exercises can promote the generation of neuronal synapses, angiogenesis and release of neurotrophic factors and neurotransmitters [6]. The tone processing can activate the brain’s default mode network, which is associated with mind wandering and creativity. The limbic system of the brain is associated with emotion and also involved in music rhythm and tone processing. Listening music can activate the brain reward system, the release of dopamine and output of signal of happiness [7]. Music can enhance memory and recognition process [8]. Signing can improve the verbal fluency and perceptibility of rhythms [9]. 

With the development of science and technology, we can increasingly understand the structure and functions of brain. More and more people are aware that, non-pharmaceutical interventions will not only benefit the older adults, but also play an important role in medical care of patients with dementia. These methods include traditional therapies, such as behavioral therapy, reality orientation and validation therapy. The latest cognitive therapies include aromatherapy and a variety of sensory therapies [1]. There is growing evidences showing that, touching and massage can supplement the medication therapy, help patients to reduce or control symptoms accompanied with dementia, such as anxiety, agitation and depression [10, 11]. Some small sample studies show that, hand massage could reduce anxiety. When dining, touching and verbal encouragement can calm down the patients, to enhance their diet and overall nutritional intake [12,13]. The skin patches may have additional advantages for Alzheimer's disease (compared with the conventional oral therapy), which can reflect the care of the caregivers and promote the communication between dementia patients and caregivers. The application of patches brings patients and the caregivers a physical sense. Cognitive training focuses on the cognitive abilities in specific areas (such as memory, attention and problem-solving skills) and improves the functions related to cognitions (such as daily living skills, social skills and behavior disorders) [14]. Although a variety of studies have shown that patients with dementia can benefit from non-drug therapy, it still needs to be validated using reliable and definite data [15]. This chapter describes the drug therapy and non-drug interventions one by one, including exercise rehabilitation, music therapy, nutritional support, cognitive and functional training, as well as longitudinal support plan and recommendations for patients with Alzheimer’s disease.   

References 

1.      Waldemar G, Dubois B, Emre M, et al. Recommendations for the diagnosis and management of Alzheomer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 2007;14:e1–26.

2.      ２           Hötting K, Röder B. Beneficial effects of physical exercise on neuroplasticity and Cognition. Neurosci Biobehav Rev (2013), http://dx.doi.org/10.1016/j.neubiorev.2013.04.005

3.      Mahncke HW, Connor BB, Appelman J, Ahsanuddin ON, Hardy JL, Wood RA, et al. Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomized, controlled study. Proc Natl Acad Sci USA 2006; 103:12523–12528.

4.      Bertone A, Guy J, Faubert J. Assessing spatial perception in aging using an adapted Landolt-C technique. Neuroreport 2011; 22:951–955.

5.      Faubert J, Sidebottom L. Perceptual-cognitive training in sports. J Clin Sports Psychol 2012; 6:85–102.

6.      Legault I, Faubert J. Perceptual-cognitive training improves biological motion perception: evidence for transferability of training in healthy aging. NeuroReport 2012; 23:469–473.

7.      Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 2011; 14:257–262. doi:10.1038/nn.2726

8.      Simmons-Stern NR, Deason RG, Brandler BJ, et al. Music-Based Memory Enhancement in Alzheimer’s Disease: Promise and Limitations. Neuropsychologia, 2012; 50(14): 3295–3303. doi:10.1016/j.neuropsychologia.2012.09.019.

9.      Baird A., Samson S. Memory for music in Alzheimer’s disease: unforgettable? Neuropsychology Review, 2009; 19(1), 85–101.

10.   Woods DL, et al. The effect of therapeutic touch on behavioral symptoms of persons with dementia. Altern Ther Health Med 2005;11:66–74.

11.   Hansen N Viggo, Jørgensen T, Ørtenblad L. Massage and touch for dementia. Cochrane Database Syst Rev 2006;18:CD004989.

12.   Remington R. Calming music and hand massage with agitated elderly. Nurs Res 2002;51:317–23.

13.   Eaton M, et al. The effect of touch on nutritional intake of chronic organic brain syndrome patients. J Gerontol 1986;41:611–6.

14.   Sitzer DI, Twamley EW, Jeste DV. Cognitive training in Alzheimer’s disease: a meta-analysis of the literature. Acta Psychiatr Scand 2006:114:75–90.

15.   Douglas S, et al. Non-pharmacological interventions in dementia. Adv Psych Treat 2004;10:171–9.

Section 1 Pharmacotherapy of Patients with Alzheimer’s disease (Delphi derived expert consensus statement)

Drugs approved for AD treatment in China include cholinesterase inhibitors (donepezil hydrochloride, rivastigmine [1,2], galantamine [3,4], huperzine A [5]) and excitatory amino acid receptor antagonist (memantine [6,7]), which are to improve cognition and functional impairment and psychological behaviors and symptoms of AD. Currently many versions of guidelines on the treatment of dementia are published in China, however, due to various factors, the therapy using these drugs is rarely applied [8,9] and standardized clinical applications are unavailable. Therefore, we introduced the clinical experiences of well-known experts from Americas, Europe and Asia, and based on their clinical practices, we reached a consensus through repeated discussions [10]. The consensus is outlined as follows: 

I. Drug Selection and Commencement of Treatment

A large number of clinical practices have demonstrated that the current method for treating Alzheimer’s disease  is reasonable and practical; clinical efficacy of ChEI therapy is apparent, and it should be used as the first-line treatment. Once diagnosed Alzheimer’s disease , start ChEI treatment; moreover, considerations should be given to the expected efficacy and potential safety, supplemented by non-drug therapy. ChEI should be clinically used for a long time.   

Different types of ChEIs have different properties, including the safety / tolerance, dose selection, prescription, metabolism and different targets in brain. The clinical benefits are to be confirmed by further evidences. The routes of administration of ChEIs differ and percutaneous administration apply to the most patients with Alzheimer’s disease , including patients who cannot tolerate oral ChEIs, those who receive a number of oral drugs with drug-drug interactions, those who cannot swallow drug tablets, and those who have expressed preference to percutaneous therapy. Patients should be informed of percutaneous therapy and they make their own decisions to receive percutaneous therapy or not.     

When ChEI treatment is applied, patients and caregivers should be informed of the expected efficacy and response (that is, stable disease condition/unchanged condition is not the reason for suspension of treatment). Experts suggest that, expectations of patients / caregivers to ChEI therapy should be concerned and they should be encouraged to receive a long–term treatment.   

II. Dose and Administration by Titration 

The goal of ChEI therapy is to achieve the best efficacy, thus, the maximum tolerated dose of ChEI should be used. For patients whose efficacy declines using a low dose of ChEI clinically, the ChEI dose should be increased to a high dose approved by the state to achieve a better clinical efficacy, this is particularly applicable to the patients who can tolerate low-dose treatment, or patients/caregivers express interests in elevated dose. When patients are in any stage of disease without dose-related adverse events, usually it requires four weeks to elevate the dose from the recommended therapeutic dose using titration method. To achieve the best efficacy of ChEI treatment, the optimal dose for each patient depends on their tolerance and the characteristics of diseases.

III. Combination therapy /alternative combination therapy/ long- term continuance of treatment and discontinuance of treatment

For most patients with moderate to severe Alzheimer’s disease , the best regimen for treatment is the optimal dose of ChEI plus memantine. Patients, when the treatment efficacy declines or adverse events occur using one kind of ChEI can benefit from an alternative ChEI, or an alternative route of administration of ChEI. The rapid decline in efficacy can be defined as MMSE score > 4 within one year, which indicates to increase the dose or use alternative ChEI. 

Drug interventions for patients with Alzheimer’s disease  should be maintained as long as possible, to maintain the patients in the best state for a long time.  Patients who undergo a treatment with stable ChEI dose should receive the evaluation at least once every six months; or when clinical changes are noticed by patients/caregiver, reevaluation should be performed. The discontinuation of Alzheimer’s disease  treatment should be individualized, to consider whether the patients can benefit from further treatment.

IV. Contraindications and Adverse Events 

Essentially, most adverse events caused by ChEIs are transient, more important than the benefits from drugs. 

Various measures may cause gastrointestinal ChEI treatment side effects, including reduced dose and increase the dose titration slower speed until symptoms disappear; or to decrease nausea, recommendations from oral administration to percutaneous treatment. ChEIs gastrointestinal adverse events should be evaluated on an individual basis.

Appropriate treatment helps to reduce gastrointestinal side effects of weight loss . If you reduce the weight becomes an issue of concern during ChEI clinical treatment should be continuous monitoring and nutritional guidance to increase the caloric intake of the way to make losing weight a minimum.

Percutaneous treatment of skin reactions occur in the use of the patch site, if they occur, should be dealt with, so that minimized, such as avoiding within 14 days of the patch stick to the exact same position again on. Suspected of having allergic contact dermatitis cases: If the application exceeds local reactions at the patch size should be; If there is evidence of a more intense local reaction; If you remove the patch after 48 hours, no significant improvement in symptoms. In this case, you may want to consider consulting a dermatologist.

The adverse events related to gastrointestinal and skin reactions should be individually dealt with, considering the time of disease and adverse events, intensity / severity and the extent of patient or caregiver’s concerns. It is difficult to reach a consensus on the drug dose-related level of gastrointestinal side effects, since a physician makes a judgment based on some factors captured at the individualized treatment.    

Considerations should be given to side effects tendencies (such as skin / GI sensitivity or bradycardia) when starting ChEI therapy and dose selection. When discussing the contraindications and adverse events, useful information on case history/tendency investigation is unavailable. In clinical practices, side effects often occur, such as bradycardia. 

V. Treatment of Alzheimer’s disease : from recent clinical trials

Experts unanimously agree that, although some interesting new information about Alzheimer’s disease  is available, the clinical use of ChEIs will not be affected.

VI. Regional Difference in Treatment of Alzheimer’s disease

Experts unanimously agree that the prevalent regional issue in clinical practice is the low rate of Alzheimer’s disease  diagnosis. There exists many obstacles for the treatment of Alzheimer’s disease , patients are not willing to accept ChEI therapy or they can accept the treatment but the dose is inadequate. Drug efficacy and adverse reactions are also involved. In the countries (e.g. Brazil, Germany, United Kingdom), where GPs is responsible for the treatment of Alzheimer’s disease , patients have the dominated role and they are not willing to receive the diagnosis and treatment. Thus, they need receive educations about the prescription from physicians.   

VII. Health Care of Alzheimer’s disease  in China 

Alzheimer’s disease  is not considered a chronic disease (requiring education) in China; therefore, patients cannot enjoy the same health insurance benefits with other chronic diseases. Patients with dementia have to go to hospital every two weeks, take prescriptions and drugs. Those patients who conform to treatment at public expenses can take medicines from hospital every four weeks. Most hospitals having the anti-dementia prescription right are the high-level ones. If patients who buy drugs at their own expenses, they can buy them for six months without restriction. Patients who can persist in long-term treatment are mostly from the highly educated families. Only single dose of drugs can be supplied in a hospital. Patients who need to take different doses of drugs should buy them in the prescription drug stores at their own expenses. Obviously, such conditions affect the long-term treatment of patients with dementia from poor families.          

The medical insurance policies differ in various cities in China. In some cities, only the hospitalized patients with Alzheimer’s disease  can be paid through medical insurance, such as Chongqing. Such a medical regulatory environment is not conducive to the long-term treatment, but also restricts the initiation of therapy and rate of treatment, which may realize in obvious regional difference in the rate of patients with dementia receiving treatment in China, and the rate in central and western regions was significantly lower than the economically developed eastern regions [8,9]. According to the sales conditions of anti- dementia drugs in seven cities in China, the proportion of patients diagnosed with Alzheimer’s disease  who received the ChEIs and / or memantine treatment was 13.9% on average (0.2% in Chengdu – 29.1% in Shanghai) and that in 2007 was 20.6% on average (2.3% in Xi’an -41.1% in Shanghai). In some small economically undeveloped cities, the varieties of anti-dementia drug is limited and even not sold. Pharmaceutical companies are not willing to invest in the education of doctors and caregivers and welfare activities. There are extensive demands in western China, which are expected to be developed and supported by Chinese experts. 

References 

1.      Wang YH, Zhang ZX, Cheng QT. [Efficacy and safety of rivastigmine in patients with mild to moderate Alzheimer’s disease.] Chin J Neurol, 2001, 34(4): 10-12.

2.      Chen X, Zhang ZX, Qian CY, et al. [Clinic efficacy and safety of rivastigmine in treatment of vascular dementia: a multi-center, open-label, randomized controlled trial.] Chin J Neurol, 2005, 38: 483-490.

3.      Hong X, Zhang ZX, Wang LN, et al. [A randomized study comparing the effect and safety of galantamine and donepezil in patients with mild to moderate Alzheimer’s disease.] Chin J Neurol, 2006,39(7)：379-382.

4.      Zhang Z, Yu L, Gaudig M, Schäuble B, Richarz U. Galantamine versus donepezil in Chinese patients with Alzheimer’s disease: results from a randomized, double-blind study. Neuropsychiatr Dis Treat 2012:8 571–577.

5.      Zhang ZX, Wang XD, Chen QT, Shu L, Wang JZ, Shan GL. [Clinical efficacy and safety of huperzine A in treatment of mild to moderate Alzheimer disease, a placebo-controlled double-blind, randomized trial.] Natl Med J China, 2002, 82 (14): 941-944

6.      Chen X, Zhang ZX, Wang Xd, et al. [Clinical efficacy and safety of memantine in treatment of Alzheimer’s disease: a multi-center, double-blind, randomized, placebo-controled trial.] Chin J Neurol, 2007, 40(6):364-368. 

7.      Hu Hong-tao, Zhang ZX, Yao Jing-li, et al. [Clinical efficacy and safety of akatinol mematine in treatment of mild to moderate Alzheimer disease: a donepzil-controlled, randomized trial.] Chin Intern Med, 2006, 45:277-280.

8.      Zhang ZX, Chen X, Liu XH, Tang MN, Zhao JH, Jue QM, Wu CB, Hong Z, Zhou B. [A caregiver Survey in Beijing, Xian, Shanghai, and Chengdu: Health services status for the elderly with dementia.] Act Acad Med Sin, 2004,26(2): 116-121.

9.      Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P for the World Federation of Neurology Dementia Research Group. Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors, Lancet Neurol. 2008, 7(9): 812-26.

10.   Zhang ZX, Yuan J. [Struggle against Alzheimer’s disease in China.] Chin J Neurol, 2008; 41:365-366.

11.   J Cummings, G Small, K Yaffe, P Scheltens, M Emre, F Jessen, P Bertolucci, H Arai, ZX Zhang, O Levin, F Manes. Alzheimer’s Disease Delphi Consensus. To be published. (Report prepared by Christina Mackins-Crabtree Senior Editorial Manager)

Section 2  The exercise rehabilitation of Alzheimer Disease

I. The positive influence of exercise rehabilitation on cognitive function

1.    Exercise rehabilitation reduces the risk of Alzheimer Disease

In order to study the effect of exercise on cognitive function, researchers from U.S. Harvard Medical School have conducted a research in the last decade, which involved more than 1200 people. Results showed that, among those who often participate in high-intensity exercises, the risk of suffering Alzheimer Disease with different degrees had a lower 40% than the average. And among those who participate in exercises at least, the risk of suffering Alzheimer Disease with different degrees can be a higher 45% than the average. Some studies also have shown that aerobic exercise can indeed enhance cognitive function. In addition, the varieties of the exercises matters more than the amounts of the activity. Those who had four or more physical activities (such as planting flowers, vegetables, walking, riding a bicycle, etc.) has only about half the risk of suffering Alzheimer Disease as compared with those who took one physical exercise or never took part in the physical exercise.

2.    Exercise rehabilitation improves the cognition of the healthy elderly

A Canadian research on health and aging has reported that the elderly who took regular exercise has a lower risk of suffering AD than that of those who took no physical exercise. Besides, the increase of physical activity level and cognitive impairment  are associated with the decrease of the risk of suffering Alzheimer Disease, which can be showed by the fact that the elderly with physical exercise of higher level has a half risk of suffering AD. [1]

3.    Exercise rehabilitation improves the cognitive ability of the patients with mild cognitive dysfunction

Exercise rehabilitation can improve the comprehensive cognition function, improve the ability of memory, attention, spatial learning, enhance the information processing speed, thus to speed up the reaction speed and improve the executive function as well as the psychomotor ability.[2]

Australia's Fitness for the Aging Brain Study has divided 170 subjects suffering memory loss or mild cognitive dysfunction into exercise group and control group. According to the recommendation guideline on physical activity by the American College of Sports Medicine (ACSM), the subjects in the exercise group should take at least 150-minute-exercise of medium intensity a week, therefore, subjects in the exercise group carried out 50 minutes walking or other aerobic exercises for three times a week, which lasted for 6 months; subjects in the control group kept the original life habit. The results showed that the cognition level of the exercise group was higher than that of the control group and the cognitive function of the control group decreased according to the normal aging speed. What’s more, the cognition level of the exercise group was still higher than that of the control group 12 months later after the end of the intervention. The research results showed exercises is effective for delaying the development of AD and the cognitive dysfunction. [3]

4. Function Mechanism

(1) Exercise rehabilitation can promote the brain plasticity

The human brain has the change function and structural characteristics (neural plasticity), making people adapt to the changing needs, and the plasticity enables us to learn and acquire new skills. Studies on animals and human suggested that physical activity promoted the plasticity of neurons in some structures, which consequently affected the cognitive function. Studies on animals have found that exercises can promote the formation of synapses, angiogenesis,, and release the neurotrophic factors and neurotransmitters. Physical activity is a trigger process, which can promote plasticity, enhance people’s reaction capacity to new demands and the corresponding adaptive behavior changes. [4]

Human brain, with high plasticity, can delay the ageing of the nerve cells to a certain extent through regular exercise rehabilitation and conscious memory enhancement training so as to reduce and delay the onset of elderly Alzheimer Disease. The number of cells "dendrites" of some healthy old man who often actively had mental activities does not decrease but increased. In addition, with increasing age, the knowledge and experiences will become richer and thus the diverse connections can be easily established. 

Proper exercise can promote neurogenesis. Adult’s nerve cells in the traditional medical concept lack of the ability to regenerate, but recent studies have shown that mice in a six-day cage exercise showed cell proliferation and neurogenesis in the brain hippocampus, which is a landmark study.[5]

(2) Exercise rehabilitation and rich environmental stimuli

Proper exercise is an essential part of a healthy life. Studies showed that the elderly with decreased ability of physical activity, less communication with the outside world, and the change of living environment, will no longer have a rich cognitive stimulation; and their decreased brain activity will result in the elevated risk of suffering from Alzheimer Disease. Exercises not only help change this state of the elderly, but also give them a happy and relieve fatigue as well as improve the body function, thus improve the quality of life. 

(3) Exercises improve the health of cardiovascular respiratory and promote the body's metabolism.

Researches have reported that the body ingested more oxygen through exercises to improve the cardiovascular health. With the increased blood flow and the number of red blood cells as well as the increasing of hemoglobin concentration, it will exert positive effect on cognition. Besides, regular sports activities can enhance the acid and alkali resistance of the brain tissue and oxidase system function, which will be conducive to the improvement of memory and thinking ability.[6] Exercise can also help to reduce impaired cognitive function caused by bacterial infection.

Practice has proved that proper physical exercise is good for health, such as insisting on walking, tai chi, and health exercises and practicing qigong, etc., which can help to relieve the brain’s suppression function, raise the activity level of the central nervous system. Therefore, elderly people should be encouraged to participate in exercises more often, such as gymnastics, tai chi, walking to enhance physical fitness, promote appetite and improve sleep. The elderly should take exercise every day, such as stretching out hand and arm, wrist, air gripper, empty punch, throwing the ball, playing fitness ball and so on.

Relevance among Physical Exercises, Plasticity and Cognition

II The exercises dysfunction of patients with Alzheimer Disease

1. Mild-to-moderate patients with Alzheimer Disease

(1) Decline in the ability of daily living

Daily life activity is essential in social life. These activities are necessary for self-care in life and maintaining health, and patients with Alzheimer Disease have a decline in the physical self-care abilities (brushing teeth, eating, taking on and off clothes, washing and toileting, etc.) and the basic abilities to use daily tools (phone, car, money, and sweeping the floor, etc.).

In daily life, we constantly interact with the environment around us. The environment is dynamic, so it is necessary to integrate a variety of objects, sports activities, exercises speed, position, etc. In the face of such environment, for example, to cross the road in the busy streets, we must quickly integrate information to make effective response through quick movement. The normal elderly people and the patients with cognitive impairment  have a decreased ability to deal with the dynamic scene, therefore it is difficult for them to quickly integrate a variety of complex information and plan the later movements, thus fail to make the quick response.[2]

(2) The difficulties in movement imitation and repetition

Patients with Alzheimer Disease and MCI, as a result of damage in movement memory and executive function (planned), suffer the difficulty in motion imitation and repetition. Movement memory (subject performed the task, SPT) , as a kind of episodic memory, can effectively distinguish cognitive impairment  between normal people and MCI patients. [7, 8]

(3) The difficulties in maintaining the posture - balance disorder

Balance refers to the body's ability to automatically adjust and maintain the posture. It can be divided into static balance and dynamic balance. Static balance refers to the control ability for human body to maintain static posture; dynamic balance refers to the ability through adjusting the posture to main balance when the external force is acted on the body. The completion of most movements in daily life is dependent on the maintain ability of static balance and dynamic balance. Patients with mild Alzheimer Disease and aMIC suffer the balance dysfunction. Through the body posture balance instrument detecting the clinical performance and balance ability, it has been found that there are significant differences between patients and normal people in the support area and the mean displacement (Mean Y) in the before and after direction.

2. The AD patients in the middle and advanced stages

(1) The AD patients in the middle and advanced stages suffer the obvious decrease in cognitive function and in visual and spatial awareness; or due to the decreasing of activities; they suffer the decrease in muscle strength and endurance. Besides, many factors including the decrease in the joint flexibility and flexibility of the soft tissue as well as the movement coordination ability can cause damage to the balance ability. The damage to the dynamic balance ability is often occurring in early period and often causes a heavier effect. If the state of illness continues to deterioration, the static balance will also be affected.

(2) Coordinated movement dysfunction

To accurately complete an action, some muscles often needed to coordinately exercise so as to generate smooth and accurate movement. When an agonistic muscle contracts, coordinated contract of synergist muscle should be involved in, which also need the support of fixed muscle and relaxation of the antagonistic muscle to ensure the movement completed at the appropriate speed, distance, direction, rhythm and strength. This kind of coordination is called muscle coordinated movement function. The AD patients in advanced stage often are accompanied with coordination movement disorder, which often show the clumsy, unbalanced and inaccurate movements.

(3) The difficulties in walking and moving - walking obstacles

Walking and moving are the most fundamental movements in daily activities. Coordination, mobility and stability are the three key elements of walking. Normal walking must be able to support the weight, maintain the balance and have the ability to making a step. The movements (foot following the ground, single leg supporting, heel off the ground, swing, etc.) require the coordinated movement of each part of body, forming a complete, fine, skilled, continuous process in walking. The AD patients who lost the walking ability due to different diseases causing the disorder have different problems and corresponding goals of rehabilitation.

(4) Acroparalysis

In the early stage of Alzheimer Disease, the exercise system is normal, and the nervous system examination has showed no positive signs, but can display the primitive reflex. In the advanced stage, the instinctive activities will be lost, and the incontinence appeared. The elderly cannot take care of themselves and pyramidal system and extra pyramidal signs and symptoms gradually appear. Finally the symptoms will present tonic or buckling quadriplegia. The intelligence of the elderly will decline comprehensively and they cannot have any conscious response  to external stimuli, known as akinetic mutism.

III The principle of exercise rehabilitation treatment for Alzheimer Disease

1. The important part of the exercise rehabilitation is on the premise of maintaining the physical health of the patients. Before the treatment, a specialist physician and physical therapist should understand patients' body health and disease status, cultural and social background, living habits and hobbies, the area and the severity of cognitive impairment , and grasp the patients psychological demand, use the Functional Independence Measurement questionnaire (FIM) or Functional Movement Screen (FMS) to evaluate patients’ body function level, and based on which, formulate an individualized exercise rehabilitation plan.

2. To provide a safe and comfortable environment and prevent and reduce secondary injury and accidents. For example, the floor of the places should not be too slippery, indoor light should be appropriate; handrails should be installed in toilet. Family training can be used in combination with the guidance of doctors, and the patients with similar backgrounds can be treated in a group in the medical institutions. On the other hand, the family members should be educated and provided with practical help. On this basis, the learning ability with different levels can be maintained for the AD patients so as to carry out the exercise rehabilitation.

3. Good mood is very important to the patient's rehabilitation; therefore, physical therapist should be kind, sincere, enthusiastic, patient when treating the patients. In order to arouse the enthusiasm of the patient's movement, interests can be improved in exercises activities, such as encouraging the patients to do exercise through games. When the patients are doing the exercise rehabilitation, encouragement should be constantly given to increase their self-confidence, motivating them to successfully complete the whole exercise rehabilitation bravely. Exercise is everywhere, and the patients should also be encouraged to do some small things within their reach to help them to experience life, rebuild confidence and satisfaction.

4. The choice of mode of exercise and intensity

It is suggested that low-to-medium intensity exercises, slightly load or no load aerobics should be chosen to achieve 30% ~ 60% of the maximum oxygen consumption, which is preferred; Heart rate should be maintained at about 100 times per minute, and it is advisable to maintain at less than 120 times per minute; For the elderly with a variety of basic diseases, especially the cardiopulmonary function disorder, it is advocated to strengthen the exercise monitoring and the rest after exercises.

5.The common techniques, exercise frequency, types of exercises and the choice of exercise time in exercise rehabilitation

Advocate the long-term, regular sports activities. In the life process of human being, any sports activities with different intensity and different duration can affect the person's cognition. Long-term exercise can improve memory and executive function, and also reduce the risk of suffering from dementia. The common techniques of exercise rehabilitation can be mainly divided into the following categories:

(1)    The exercise therapy to maintain joint mobility and enhance the muscle strength;

(2)    The occupational therapy to strengthen the muscle coordination ability and improve the capability of the daily life;

(3)    The rehabilitation training therapy to restore balance and walking function;

(4)    The aerobic exercise therapy to increase muscular endurance and cardiopulmonary function;

(5)    Exercise and learning plan to improve exercise skills and cognitive function;

(6)    The music exercise therapy with the combination of music rhythm;

(7)    Traditional Chinese breathing exercises like medical gymnastics, guided health exercise, tai chi, eight trigrams boxing, five-animal exercise, etc.

6. The therapeutic effect evaluation of exercise rehabilitation: due to the different research designs, methods and plans, cognitive evaluation applied to different methods, different conclusions can be made. Besides, combined with the different historical backgrounds (exercise frequency, time) in social status, identity, culture and exercises, the effect of one-time exercise can be varied greatly from individuals.

IV. Cognitive impairment and exercise rehabilitation plan for AD patients:

1. Hand rehabilitation exercise

The patients should often exercise their fingers to relax the brain: the so-called “ten fingers with the heart" refers to the close relation between the ten fingers of human being and the heart. Because each finger has a meridian at the same time, and it has direct link with the deep of the head, face and brain through the limbs, exercising the fingers can stimulate the different centrals in the brain (as shown in figure 2). Elderly people play ball for a long time, or they often use finger spinning ball or walnuts, or do hands stretching exercise, which can make the fingers, palms, wrist bent flexibly, promote the exercise of the upper limb muscles including the fingers, wrists, elbows, etc. Those kinds of finger exercises can prevent and alleviate the symptoms of the elderly such as weakness, shivering, grip strength loss of the upper limbs caused by the degenerative disease. Besides, hand exercises may have a very good effect on the brain. When playing the health care ball, the mind and thinking of the elderly can be focused on hand, so that the cerebral cortex neurons can be stimulated, the blood circulation promoted, mental flexibility enhanced, the ageing of the nerve cells delayed, and to some extent, Alzheimer disease can be prevented and improved.

Finger exercise:

The first group:

(1) ① have expiration and clench a fist. ② sniff the air and let go of your fingers, which can make the mind relaxed. (2) Using a forefinger and thumb to knead the other fingers, starting from the thumb, each finger lingering 10 seconds, which can help the patients to keep in a good mood. (3)① sniff the air and clench a fist with force. ② have expiration with force and at the same time sharply stretch the little finger, ring finger, middle finger, index finger in turn. The right and left hands should do the exercise many times one after another. Note: when you clench the fist, your thumb should be grasped in the palm. (4) Stimulate the acupuncture points of the fingers to reinforce the effect. Use forefinger, middle finger, ring finger and little finger in turn to press the thumb. (5) Stimulate the meridians, with the thumb pressing each point of the fingers. (6) Stretch the wrists straight and make five fingers together, and then open, do this several times.

The second group:

(1)  Raise the elbow to be parallel with the chest, with fingers of two hands relative to each other and press each other, especially the thumb and little finger should be pressed with much force, then take a deep breath. Press the fingers with force when breathing out the air. This kind of exercise is also effective for respiratory system diseases, gynecological diseases, and low back pain. (2) Raise the wrist to the same high position with the chest, with fingers of the two hands correspondingly hooked and makes an effort to pull on both sides. This kind of exercise is also effective for high blood pressure. (3) The thumb of the right hand with the index finger of the left hand or the index finger of the right hand with the thumb of the left hand touch each other alternately, then the fingers of the two hands can have the exercise in the alternating touching. Accelerate the speed if the proficiency is acquired. Again the thumb of the right hand with the middle finger of the left hand or the thumbs of the left hand with the middle finger of the right hand touch each other alternately, and the rest exercise can be deduced by analogy until the little finger touches the thumb. This kind of exercise can exercise the motor nerve to prevent brain aging. (4) Two hands clasped with crossed fingers (fingers pointing to the palm), and the wrist force down. (5) Two hands clasped with crossed fingers with fingers pointing to the fingers, and twirl back and forth around the wrist. (6)  Raise the elbow up to the same high position with chest, and bend each finger with force in sequence, and push hard on the Laogong point. This kind of exercise can make the intestines and stomach healthy..

The third group:

More stimulus methods are needed. Small iron ball or walnuts can be used as tools, and the specific practices are as follows: (1) hold the ball in hands, forcibly hold it and breath out the air at the same time, then take a deep breath and open the hand. (2) Hold two balls in the hand, and rotate them from left to right in turn. The elderly has experiences, and when he or she has trouble and discontent, he or she can use this method to calm down. (3) Hold the ball with two palms and press it with force from both sides, with the left hand firstly pressing the left hand and then making the left hand upper the right hand, exercising the wrist when pressing. (4) Place the ball with index finger and thumb, and exercise the fingers with right hand and left hand in turn. (5) Place the ball between the fingers, making it rolling back and forth.

The patients should often do the delicate activities of fingers tip of the two hands, such as arts and crafts, sculpture, drawing, paper-cut, typing, playing a music instrument with finger, massaging hands, clenching fists, twisting fingers, pushing and wrenching fingers, flicking the fingers, beating up, inserting fingers, wrist twirling, which can expand the brain blood flow, promote the blood circulation, effectively massage the brain and help the brain actively functionalize so as to prevent and improve Alzheimer disease.

Clapping for a long time can promote blood flow, increase the body heat so as to enhance physical fitness, prevent many chronic diseases, which is also effective for preventing the elderly Alzheimer disease. Clapping hands in general should be done twice a day, in the morning and evening. At first, the clapping force cannot be too fierce, and it should be done step by step. In addition, this kind of therapy should be avoided in many situations, such as eating too full or just after the meal, as well as between two meals, so as not to affect the digestive function. Generally speaking, the normal person should take 5 minutes clapping hands every morning, which can stimulate the energy throughout the day. It should not be too much noise, and the patients can hunch the hands to be an arch, using the empty palms clapping. The elderly are weak, so they should clap your hands while at the same time take a walk or step, otherwise, the blood will be too much filling the two hands, and then the feet will feel weak and impotence.

2. The head and neck exercise

This kind of exercises can not only make the rotation of the spine smooth, prevent the elderly suffering from the symptom of incomplete vertebral artery circulation, but also can delay the cerebral arteriosclerosis, prevent and improve the elderly Alzheimer disease. Its procedure is as follows: Spin the head for one hundred times from left to right and for another one hundred times from right to left, which is simple but effective and can be done anywhere at any time.

Ten fingers of the two hands can do the “comb” exercise 12 times from the forehead hairline to the back hairline; Then the two thumbs press on the temples, and the rest four fingers against the top of the head, from the top down, and from bottom to up do straight-line massage 12 times; Finally, two thumbs press on the temple, with a strong force to do rotary press, first turn clockwise, then turn counterclockwise for 12 times respectively.

3. Lips and teeth exercise

More than 40 muscles in the face can be exercised along with rhythm, which is advantageous to the health care of face and the tissues and organs in the mouth. Lips exercise can also do well for the health care of the brain, which to a certain extent can prevent the brain failure and is helpful for preventing and

• Open and close lips method: open the mouth to a maximum, and make the "ah" sound, then close the mouth, and this should be done rhythmically for 100 times without stop every time or lasting for 2-3 minutes.
• Rub the lips method: close the lips, and two fingers of the right hand rub in the outside of the lip brush until there is redness, fever in the lips. It can improve the blood circulation in the oral cavity; enhance the resistance of the oral cavity and teeth.
• Close the lip and bulge the cheek method: close the lips and blow outward, bulging the cheeks with a finger gently massage the cheek for 1 to 2 minutes. This can prevent the atrophy of the cheek muscles.

4. Add some weight training courses every week

A new study conducted by University of British Columbia, Canada has found that lifting weights contributed to the improvement of the cognitive function of the elderly aged from 65 to 75 years old. Medical doctors of the university said the old man can do simple dumbbell exercise, which can help to improve their decision-making ability. In addition, the dumbbell exercise will improve the old man's walking speed. The walking speed of the old man is an important index to reduce mortality. A number of early studies showed that walking and swimming can improve cognitive function in the brain. But many elderly people, due to the physical inability, are unable to complete these exercises. At this point, the old man can instead do the dumbbell resistance training, or lift heavy objects by hands. Weight training has undoubtedly helped the deep feeling stimulation of neuromuscular, strengthened the understanding and control of muscle exercise for the elderly and at the same time, the endurance training with low intensity is good for the brain, which can prevent and improve Alzheimer disease.

5. The systemic rehabilitation exercise:

Take a brisk walk for an hour in the place with fresh air every morning and evening. Brisk walking can exercise the tension muscle at the bottom of the waist, improve the oxygen uptake, and help to stimulate the brain cells, prevent brain cells degeneration, which also has achieved an ideal effect on the prevention of Alzheimer disease.

Walk backwards: take an exercise in reverse order. This kind of exercise can stimulate the nervous system of human being, increase the body's balance and sensitivity, increase physical coordination and slow down the aging brain. In walking, the patients should choose an open and smooth road, walking backwards for a certain distance. But the patients must keep the body's center of gravity, preventing the phenomenon of falling because of the unsteady center of gravity. Step back, and move the body’s center of gravity after the feet stand firmly to the ground. The body’s centre of gravity falling to one foot on the ground, and then the other foot can off the ground.

Slowly crouch: this is an exercise for brain nerve, which can exercise the muscles of neck, back, waist and legs, serving many functions at one stoke. Practice: separate the feet to the same width with the hip, with hands at your sides, slowly bend your knees and squat until thighs paralleling to the ground. Arms stretched up front at the same time to the same high position with the shoulders and then slowly put down. Keep the head up when squatting down and at the same time sit backwards to avoid the knee over the toe.

Lift heel: the most distant nerve stands in the foot, so slowly lifting up and down can exercise the control and coordination ability of the nerves. Practice: the body stands upright, with hands resting on the hip. The leg muscles should give a force and lift the heel off the ground for about 5 centimeters. Still keep the body upright, don’t swings, trying to get the muscles in the whole body have a sense of tension. The patients can choose to do the exercise in the places with a wide vision like the outdoor, before the window, to look far into the distance, which also helps to alleviate eye fatigue.

Walk a straight line: exercise the body coordination, sensitivity, which helps to prevent the degradation of the nervous system, so as to prevent Alzheimer disease. In the process of walking, the patients should focus and control the placement of the feet, allowing it to be a straight line. By swinging the arms, spinning the waist and hip exercises, and under the premise of ensuring the body balance, the feet should walk in a straight line.

The elderly who suffered cognitive impairment or AD should at least walk five miles (8 km) once a week to maintain the brain and delay the decline of the cognitive abilities, while the healthy elderly people should at least walk 6 miles (9.65 km) once a week to maintain the brain and significantly reduce the risk of cognitive decline. The existing researches have found that if the elderly want to prevent or delay the cognitive decline and prevent the AD development, they should take exercises at least 3 times a week, with 40 ~ 60 min for every time, and they should take no less than 150 min moderate physical activity a week.[9]

6. The Tai Chi exercise (as shown in figure 3) shows a certain effect on the brain function. Tai Chi, as a kind of aerobic exercises, uses the coordination movement of eye and hand in the process of the exercise, with the sight following the movement of the fingers, which through the whole body exercise from the fingers to feet to achieve the concentration and play a positive role in improving the memory ability. Having the aerobic exercise for more than half a year can greatly improve the FAB function of the frontal lobe and the fluency of the language.

Fig.3

7. The other Chinese traditional bodybuilding exercises such as guiding life-nurturing exercise (as shown in Figure 4) are full of the Oriental inclusive concepts, with the combination exercise of the concept, air, shape and spirit, which meets both the physical and psychological requirements of human body, and has a very important positive effect on the harmonious coexistence of the body parts of human being. It also has an obvious improvement effect on the overall quality of life of the elderly including the cognitive abilities. [10] The elderly should stick to learn or practice 1-2 times a day, every time lasting about half an hour.

Fig.4

8. The rehabilitation training of cognitive function has many aspects, which can be targeted respectively from the different aspects of attention, reaction ability, physical mobility ability, information integration ability. For AD patients with cognitive impairment, some training scene models should be designed, with these situations involving and training a series of abilities of the patients. That includes the preliminary collection of the outside information such as sound, light, electricity, heat, far and near, dynamic and static, the environment changes, etc., and the integration and analysis of the outside information and then accompanied by some possible instinctive reactions and exercise reactions after brain processing and planning for the outside information. Psychophysics expert at the university of Montreal, Canada, Professor Jocelyn Porter used the invention "Neuro Tracker (as shown in figure 5) to train the athletes, and found that the cortex thickness in some areas of the athletes’ brains could be thickened. [2] Researchers have been exploring the methods for the elderly people or those who suffered attention problems, and this discovery provided a new way for us. In terms of the development of exercise rehabilitation at present, two practical methods exist: one is to make use of the feeling games software similar to Neuro Tracker or Xbox and adopt the training method with the combination of entertainment and rehabilitation; the other is actualize the virtual games through the design and revivification of the environment scene to create a real atmosphere in the body feelings game in which the abilities such as the attention, response speed, body movement and information integration are challenged so as to achieve the goal of rehabilitation training. As participants gradually adapting to and accepting the rehabilitation training method, or the cognitive function gradually improved, many other training methods can be used, such as adjusting the target object's shape, type, size, color to arouse repeated stimulation, or changing the trajectory and the speed of the target object, or gradually decreasing or increasing the movement range of the space. The participants can be requested to chase the objects and at the same time under various interference or unstable conditions to do some other exercises, such as high-speed movement, crossing the obstacles, identifying the password and interference, and so on. At the same time, it is important to note that when changing the distance between the patients and the scene of the training, different rehabilitation effects will be achieved, which also provides the possibility for the complex changes in the form of rehabilitation training. This is a new method and new field full of imagination and creativity, which deserves more attention and practice [11].

Fig.5

Guo Jiangzhou, Zhang Zhenxin

References:

1.      Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 2001;58(3):498-504.

2.      Legault I, Faubert J. Perceptual-cognitive training improves biological motion perception: evidence for transferability of training in healthy aging. NeuroReport 2012; 23:469–473.

        3.      Lautenschlager NT, Cox KL, Flicker L, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a                       randomized trial. JAMA 2009; 300(9):1027-1037.

4.      Hötting K, Röder B. Beneficial effects of physical exercise on neuroplasticity and Cognition. Neurosci Biobehav Rev (2013), http://dx.doi.org/10.1016/j.neubiorev.2013.04.005

5.      van Praag H, Christie B R, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences 1999;96(23):13427-13431.

6.      Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144(2):73-81.

7.      Zhang YM, Han BX, Verhaeghen P, Nilsson LG. Executive Functioning in Older Adults with Mild Cognitive Impairment: MCI has Effects on Planning, but not on Inhibition. Aging, Neuropsychology, and Cognition, 2007;14(6):557–570.

8.      Nilsson LG, Bäckman L, Erngrund K, et al. The Betula prospective cohort study: Memory, health and aging. Aging, Neuropsychology and Cognition, 1997;4:1–32.

9.      Yuki A, Lee S, Kim H, Kozakai R, Ando F, Shimokata H. Relationship between physical activity and brain atrophy progression. Med Sci Sports Exerc 2012;44(12):2362-8.

10.   Kohn, Livia. Chinese healing exercises: the tradition of Daoyin. University of Hawaii Press, 2008.

11.   Legault I, Allard R, Faubert J. Healthy older observers show equivalent perceptual-cognitive training benefits to young adults for multiple object tracking. Front.Psychol. 4:323. doi: 10.3389/fpsyg.2013. 00323

Section 3 Music Therapy for Alzheimer Disease (AD)

I. Music Therapy

Alzheimer Disease (AD) is a kind of nervous system degenerative disease which worsens as it progresses with the cause difficult to diagnose and its main clinical symptoms are the memory disorders and impaired cognitive function. At present, the treatment of Alzheimer Disease still focus on the drug treatment which however can only play a limited role in alleviating the major clinical symptoms of the disease. Therefore, the related non-drug therapy began to gradually step in disease treatment in order to slow down the deterioration of cognitive function in patients and to improve the patient's problem behaviors, improve the patients’ quality of life so as to help the patients to live a life with dignity in the progression of the irreversible disease. Music, as a form of non-drug therapy, plays an irreplaceable role. 

Music therapy began in the middle of the 20th century. During the Second World War, the medical staff from the United States Military Hospital found by accident that music can soothe the emotion of the wounded, and with the improvement of emotion, the mortality rate also gradually reduced, then the music was widely used in American hospitals, so as to improve the patient's psychological and physical function. As musicians and psychologists have gradually stepped in it, this kind of treatment gradually formed a new interdiscipline - music therapy [1].

Music therapy can be roughly divided into two kinds. One is active music therapy, in which the patients together with the music therapists actively take part in the music therapy activities through singing, playing musical instruments, dancing and other forms. Another is receptive music therapy, mainly through the way of passively listening to music, and the music can be played though record or be a live performance, which should be chosen by the music therapists according to the situation of the participants.

II. The intervention form and function mechanism of music therapy

Clinical studies have found that AD patients are typically suffering very serious damage in left brain, and the functions such as language, words, logical analysis which is in the charge of the left brain are affected greater, while the functions such as singing, dealing with rhythm, melody, music, pictures that the right brain is responsible for has maintained good. According to this, the functions that the right brain responsible for could be developed through music, so as to have compensatory effect on the damaged functions of the left brain.

1. Sing a song

In clinical applications, we often see a phenomenon in which some patients have serious difficulties in expression with slurred speech, or it is difficult for them to find the right words to express themselves, but when hearing the familiar songs, patients are able to sing the song along with the music [2], and show no obvious errors in terms of pitch, rhythm, melody and lyrics. This shows singing can improve the patient's verbal fluency and susceptibility of rhythm. Study found that "sing" can help the patients to better remember the lyrics of the old songs than “say”, and it also reflects that music can enhance memory re-cognition process [3].

Singing itself also has therapeutic effect to the body, the mechanisms are as follows: (1) singing is beneficial to strengthen the diaphragmatic muscle activity, and helps to exercise abdominal breathing: diaphragm is the main respiratory muscle for humans, and singing can help the diaphragm to move up and down, which contributes to the exercise of the main respiratory muscle, so as to increase the lung capacity and improve lung function;(2) singing can produce the resonance with the respiratory frequency so as to improve the respiratory function: the human body is composed of many regular vibration systems, such as the beating of the heart, the relaxation of the lung , gastrointestinal peristalsis, brain wave motion and autonomic nervous activity. Those vibration systems have their own rhythm and frequency, and singing can produce the rhythm resonance with the body thus plays a therapeutic massage role that makes the function of body organs improved; (3) singing exercises the cardiopulmonary function: when human body is breathing quietly, the inhaled and exhaled air is known as tidal volume, which is about 500 ml, while the breath quantity every time during singing can be increased to thousands of ml, which not only improves the lung function, exercise chest muscle, but also promotes blood circulation and enhances heart function;(4) singing can promote the brain to secrete "happy hormones”, and the rise of happy hormone levels can relieve pain, boost mood, promote the blood circulation and stabilize pulse, so that the patients can express the happy emotion or bad feelings through singing to release the unhappy emotion in the heart, which can contribute a lot to adjusting the mood and releasing the pressure.

In addition, for AD patients, singing can remind them of the past memories. For there is a corresponding representative song in each age grade, the patients can easily find the old time accompanied by the song in so many happy memories. Research has shown that music memory can be kept in the brain for longer time than those memories concerning no music. [2].Accompanied by music, and traced back to the happy memories in the past, the patients can have relaxed and joyful emotion, which can not only exercise the memory ability of the patients but also relieve the anxiety and depression caused by the disease.

2. Play a musical instrument

Playing musical instruments such as drums and piano can exercise the motor coordination ability in patients with bulky muscle and fine muscles, which can help the patients to expand the scope of exercise so as to enhance endurance, strength, and the function of hand as well as the finger flexibility [4].At the same time, playing a musical instrument is a kind of rhythm training, through rhythm training, it can help patients to have brain information processing. Drum training, for example, is a very popular musical instrument, because even those who haven't instrument experiences before can quickly grasp the main point of the drum, and under the guidance of music therapists, the patients can quickly learn to play the drum with simple drum rhythm, and will soon be able to participate in performance. Drum therapy has a very good effect on the AD patients whose brain lacks the information processing function. Because the rhythm itself has the characteristic of forecasting, providing an opportunity for the patients to grasp and to knock out the drum rhythm in a right way. A patient can't raise his/her hand to pick up things, perhaps that’s because he can't organize and carry out the thinking of this behavior, while playing the musical instrument has little need to process thinking, and it can influence the brain's motor nerve center, therefore, drum therapy can attract the patients’ attention to focus on the rhythm to help them to process information and enhance the time awareness as well as strengthen the physical exercise function. Sound processing can activate the default mode network of brain, which is associated with the mind wandering and creativity.

3. Listen to the music

With the progression of the disease, AD patients would gradually appear bad emotion and behaviors, such as anxiety, agitation; under this kind of emotional state, the words and speeches of the caregivers can hardly have very good calm effect on the patients. When the words cannot work, music favored by or familiar with the patients could be played more often, because the familiar songs can provide the patients with a sense of security and happiness, and with this emotion, the patients can gradually calm down and reduce the occurrence of adverse emotions such as anxiety. The limbic system of the brain has association with emotions, but it also involves the processing of the music rhythm and tone. Listening to the music can activate the brain's reward system and release the dopamine in brain, so as to output the happy signals [5, 6].

4. Take part in music group activities

Whether it is a small team singing, playing musical instruments, or listening to music, to AD patients it provides a platform for them to share the communication of feelings. In the music group activities, the patient's social behavior and communication ability can be improved, which can reduce their loneliness and avoidance behavior and encourage patients to express and communicate each other's feelings and thoughts so as to bring positive impacts, at the same time stimulate the patient's cognitive processes like judgment, thinking as well as improve the patient's problem solving ability.

III. Music therapy for AD patients in different stages

1. The music therapy for patients in early stage

The AD patients in early stage have showed the symptom of memory declining significantly, with other symptoms not obvious, and there is a slight change in such aspects as thinking and learning ability. They can have the common daily communications and carry out daily life activities. In the early stage, the therapy intervention for the patients should focus on the exercises of cognitive function, such as attention, memory, analysis, understanding of judgment, etc. Patients in this stage will have the bad feelings such as frustration, anxiety and helplessness because of a reduction in the ability to memory things, therefore, more emotional support should be given to the patients in this stage to make them feel the strong love and care from the families and friends, so that they can have the courage and a sense of security to face up with the future.

For patients in early stage, the music therapy activities are as follows:

(1) Music albums technology

Activity form: group activities (about 4-8 members)

Applicable group: mild AD patients.

Purpose:

To train the patients with memories of the past, enhance the memory of the original memory; through participation in music performance, gain the psychological support from the group members and through the glorious achievements of the past memories, enhance patients' sense of value and personal achievement.

Activity time: 50 minutes

(2) Songs memory technology

Activity form: groups or individual

Applicable people: mild to moderate AD patients

Activity process:

Before the activity, firstly the music therapist should understand the patient's music preferences, then choose the right music types for patients in different periods, which can be divided into three types: early adulthood, middle age and old age, and the music therapists should guide patients to have memory recalling. In general, for the elderly aged 60 - 80 years, the representative songs familiar to them include "In the Distant Place", "Aobao Meeting", "Let Us Sway Twin Oars", "Honghu Lake Water Waves ", "Sing a Folk Song to Party". A female patient, who has been in the severe stage, after hearing the song "In the Distant Place", can sing softly following the melody together. When recalling the past memories, she said very clearly "we all liked to go to the park to eat watermelon, and many young people took a watermelon to the Zhongshan Park". After her husband explained, we know that she remembered some scenarios when they were young. At that time, young people went to the park to eat watermelon, which is a kind of fashion, just like young lovers like to eat Haagen-Dazs ice cream now. So an old and familiar song can often trigger the nostalgia memories, and the memories recalling can also enhance a sense of reality and existence.

Activity time: 45-50 minutes

(3) Super music memory therapy

Music therapists choose the classical songs in the Baroque Ages to make the patients feel relaxed both physically and mentally. Through listening to music, the right brain activity can be stimulated, and then stop playing the music, instead let patients to read following memory. After learning, the music therapists can play different types of music; let the brain recover from memory activities.

Applicable people: mild to moderate AD patients

(4) Music imagination training

Activity form: groups or individual

Applicable people: mild to moderate AD patients

Purpose: train the imagination power of the patients, and develop the images function of the right brain to prepare for the training of memory

Activity process: music therapists select the appropriate music, then guide the patients to relax both physically and mentally. Under the stimulus of music, the patients should describe a certain scene to let the patients have active imagination.

Activity time: 30 minutes

(5) Drum therapy

Activity form: groups or individual

Applicable people: mild to moderate AD patients

Purpose: through the various combinations of exercises with different duration rhythm to enhance the patient's sense of time and space.

Activity process: According to the patient's ability, the music therapists arrange various combinations of rhythm from easy to difficult, then teach the patients to have practice; in order to increase the sound effects, the patients can practice the rhythm on hand drum, which can not only train the patient's sense of time and space, but also can stimulate the patient's hand muscles and nerves through the contact of palms and the drum head.

Activity time: 45 minutes

2. Music therapy for patients in middle stage

Patients in the middle stage have difficulties in expressing speeches, and completing daily life activities. Some patients can not find the right words to express themselves, or they express in a very chaotic way, which is difficult to understand. They become no longer pay attention to personal hygiene, and they don't know how to choose proper clothes, because it seems that any dress casually can wear in their body, and they have no intention to taking a bath, even refuse to take a bath. They become angry easily and their behaviors become different from before. For the patients in the middle stage, the music therapy intervention should focus on creating a peaceful environment, helping the patients to participate in music activities with interest so as to reduce the extreme behaviors of these patients.

 (1) Relaxation therapy by listening to music

When patients started to get angry, wanted to lose his temper or conducted the bad behaviors such as agitation, the families and caregivers should be suggested not to blame them by saying the words like “what's the matter with you? How can you lose your temper again?” and not to comfort him by saying too much words. Instead, the families or caregivers can play the songs that the patients is familiar with or that with slow rhythm so as to make the patient calm down.

(2) Chopsticks rhythm exercise

Chopsticks are the eating tool with the most Chinese national characteristics, and everyone is extremely familiar to chopsticks. For AD patients, chopsticks are also the familiar eating tool, even when the patients have reached the middle or the advanced stage, they still know how to eat with chopsticks. Therefore, chopsticks, as a kind of rhythm instrument, will not cause fear or worry for them, then they can naturally pick up the chopsticks for tapping, and the music activity with chopsticks tapping the body parts like hand, shoulder, waist, leg in accordance with the music is known as chopsticks music exercise.

Based on the appropriate music and according to the rhythm, speed of the music, music therapists, designed the tapping movements of the chopsticks to a set of simple and artistic gymnastics to exercise the body's flexibility and coordination of the patients. At the same time, the activity with the combination of music and mobility also can bring the joyful mood to patients.

3. Music therapy for the patients in the advanced stage

Typical symptom of patients in advanced stage is the loss of ability to speak and express ideas, but related studies have found that even the patients have reached the advanced stage, they still have some sense of self-consciousness. Therefore, for caregivers, the main task in this stage is to make the patients to live a life with dignity and decency to enjoy the last period of life.

Music therapy at this stage mainly is to help the patients to maintain good emotional state. However, because the patient’s cognition has suffered severe damage, such as difficulty in speech understanding, poor hands coordination, he (she) found it hard to play the instruments or sing like the first two stages, so the form of music intervention is very limited. And the songs the patients fond of or the folk songs, drama, duet songs and dances as well as allegro or anything that the patients like or familiar with should be played at this period more often. Although the patient's disease symptoms have already become very serious, he (she) still has the self-awareness, and feeling the love from his family and the warmth is the greatest comfort for the patients in the final phase of life.

IV. Summary

For AD patients, the constant deterioration of the disease at present cannot be controlled by the drug therapy or non-drug therapy, however, when it comes to non-drug therapy, especially the music therapy, obvious positive role has been played in improving the life quality of the patients, so that the patients can live a happy life with dignity even under the shadow of disease.

Wang Llinlin, Zhang Zhenxin

References:

[1]    Zhang HY  Music Therapy Foundation, China Electronic Audio - Video Press, 2000

[2]    Baird A., Samson S. Memory for music in Alzheimer’s disease: unforgettable? Neuropsychology Review, 2009; 19(1), 85–101.

[3]    Simmons-Stern NR, Deason RG, Brandler BJ, et al. Music-Based Memory Enhancement in Alzheimer’s Disease: Promise and Limitations. Neuropsychologia, 2012; 50(14): 3295–3303. doi:10.1016/j.neuropsychologia.2012.09.019.

[4]    Gao T, Rationale of Music Therapy, World Book Publishing Corporation (2007-04)  

[5]    Menon V, Levitin DJ. The rewards of music listening: response and physiological connectivity of the mesolimbic system. Neuroimage, 2005; 28, 75–184 (2005).

[6]    Salimpoor VN, Benovoy M, Larcher K, A, Zatorre RJ. Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 2011; 14:257–262. doi:10.1038/nn.2726

Section 4 Nutritional Support Treatment of Alzheimer's Disease

I. Alzheimer's Disease and Nutritional Support

Alzheimer's disease is organic or metabolic disease of brain and a kind of chronic progressive neurodegenerative disease. The nutrition of Alzheimer's disease is a factor that may delay in the occurrence of this disease and a guarantee to maintain the basic quality of life of patients. The patient's nutritional status may also be related to their clinical prognosis.   

Research findings of foreign scholars showed that insufficient intake of some nutrition-related factors such as folic acid, niacinamide, vitamin C is associated with Alzheimer's disease and adequate and balanced intake of nutrients can prevent the occurrence of Alzheimer’s disease. Therefore, to look for and supplement the nutrients related to Alzheimer's disease has become one of the hot issues in the nutritional science.  A research published in Archives of Neurology in April 2010 indicated that, diets rich in nuts, fish and vegetables and low content of low-fat dairy products and red meat can prevent the occurrence of AD. To evaluate the relationship between food combinations rather than single nutrient and risk of AD, investigators conducted study on the diet data obtained by food frequency questionnaires and two multi-race queues are involved in this survey. AD happened in 253 subjects during an average follow-up period of four years. The investigator calculated the dietary pattern according to the difference in seven kinds of nutrients most related to AD risks in the literature. Results showed that, dietary pattern with rich ω-3 polyunsaturated fatty acids, ω-6 polyunsaturated fatty acids, vitamin E and folic acid, and lower saturated fatty acids, was strongly related to the prevention of AD. After adjusting the age, education, race and gender, the protective effect of dietary pattern was unchanged. Further analysis after adjusting the smoking status, body mass index, energy intake, complications and apolipoprotein E genotype, the protective effect was not significantly weakened. On the basis of recently available clinical evidences, nutritional factors associated with AD are as follows:  

1. Foods rich in choline and nicotinamide

Studies have shown that Alzheimer’s disease is related to the intake of choline and nicotinamide. Nicotinamide can stimulate brain blood circulation and enhance the rehabilitation of brain cells for most AD patients. The poor learning and memory ability of AD patients are possibly associated with inadequate acetylcholine in the body.  Choline is a kind of B vitamins, which plays a variety of roles in cell membrane phospholipid metabolism and is concerned for its potential effect on neurological diseases. As a precursor of phosphatidylserine and phosphatidylcholine , phospholipid is located on the cell membrane (including the nerve cells). Because the transmission of nerve impulses needs choline, choline and acetic acid could bind to form acetylcholine, which can cross the gap between nerve cells for conduction of nerve impulses. Lecithin is a raw material in the brain to transform to choline and people can take in lecithin from foods to prevent AD. In the daily diets, soybeans and their products, fish brain, egg yolk, pork liver, sesame seeds, yams, mushrooms, peanuts are natural foods rich in lecithin. Regular intake of them can provide nutrition for the brain, enhance intelligence and slow down mental decline. Therefore, taking choline and nicotinamide -rich foods may be helpful for AD patients. At present, the reference intake of choline in adults in China is 500 mg per day. Foods rich in choline are eggs , egg yolk , liver , soybeans, wheat bran , cheese , barley , maize, rice, millet , brewer's yeast , etc., and foods rich in nicotinamide are animal liver , kidney, lean meat and so on.

2. Foods rich in folic acid and B vitamins 

The incidence of AD is also related to deficiency of B vitamins and folic acid. An earlier study conducted by Goodwin et al found that there is a correlation between nutrient intake and cognitive function. Comparing with the control group, the incidence of AD was higher, and elevated serum homocysteine ​​level would appear in the patients. The folic acid and vitamin B₁₂ can lower the in vivo homocysteine ​​level, so the supplement of folic acid and vitamin B₁₂  may prevent the occurrence of AD. In a clinical study with duration of 9 years, the incidence of AD among the older adults with diets rich in folic acid was half reduced as compared with those with intake of folic acid lower than the recommended amount. Investigators conducted investigation on the diets of 579 volunteers (353 men and 220 women volunteers) and none of them suffered from Alzheimer's disease at 60 years old, but after a 9-year of follow up, 57 volunteers suffered from Alzheimer's disease. A comparison of the daily nutritional intake between the AD patients and non-AD patients showed that, the incidence of AD among patients with diets rich in folic acid was reduced by about 60%. Foods rich in folic acid are oranges, bananas, green leafy vegetables, asparagus, broccoli, animal liver and various beans and peas and bread with folic acid fortification. 

Although the American Heart Association did not recommend widespread use of folic acid supplements to reduce the risk of heart disease and stroke, a healthy, balanced diet was recommended, including at least five servings of fresh fruits and vegetables every day, guaranteeing the daily intake of folic acid. 

It was also found (Solfrizzi, et al) that a high intake of monounsaturated fatty acids appeared to protect the body against the cognitive decline occurring with growth in age. Some researchers found that the vitamin C level in blood and intake was related to the individual’s cognitive function. A study (Perkin et al) found that, among 4809 subjects, after adjusting the factors such as age, education level, etc., the reduction in serum vitamin E per unit cholesterol was associated with the increase level of memory decline. Studies showed that, patients with severe AD after intervention using large dose of vitamin E were improved.

3. Soy and its products 

Soybean is a traditional tonic food. Soybean is known as the king of beans, approximately 40%~50% of protein content. The protein content per kg soybean is equivalent to that of 2.5 kg lean pork or 2 kg lean beef, therefore, the soybean is called “green milk” or “plant meat”. In addition to rich protein, soybeans also contain phospholipids, carotene, B vitamins, niacin, folic acid, choline , saponins and iron, phosphorus , calcium, potassium and other nutrients. Soybean is also rich in active substances such as isoflavones, saponins, oligosaccharides, etc.. 

Studies showed that soy isoflavones have a certain health care effect of brain, and its chemical substances are extremely stable, which will not be destroyed regardless of fried, boiled, stewed, therefore, frequently eating soybean can not only take in vegetable protein, but also have effect on preventing dyslipidemia, arteriosclerosis and AD. 

The soybean is rich in protein, phospholipids, unsaturated fatty acids, calcium and vitamins. The glutamate in the protein is the material basis of physiological activity of human brain. One hundred grams of soybean contains about 6.6 g of glutamic acid. The phospholipid content in the soybean is also very high, about 2% of the total weight. Soyabean lecithin can help transport cholesterol, clear away the cholesterol on the blood vessel wall, and prevent cerebral arteriosclerosis and vascular dementia. 

Soybeans can be made into various products for eating. For older adults, it can be made into soybean milk as a breakfast drink. Soybeans can also be made into tofu, bean curd, bean curd stick, dried bean curd, fermented soya beans, etc..

4. Whole Grains

The whole grain foods that are ever withdrawn from the dinner tables in the city are increasingly becoming the new darling of people, especially people is gradually paying attention to the brain “health care” function of coarse grains for middle-aged and elderly people. But there is still lack of evidences of its effectiveness. Many studies on oats were conducted at abroad. Oat is also known as wild wheat, sparrow wheat. According to modern scientific analysis, edible part of oat per 100 g contains 15.6 g protein, 6.7g fat, 66.9g carbohydrates, and high content of calcium, phosphorus, iron, vitamin B₁, vitamin B₂, niacin, etc.. Recent research indicates that, Avena nuda contains linoleic acid which is extremely beneficial to human body, so, it can inhibit the increased cholesterol level.

Studies conducted by some medical scientists showed that, sometimes eating 60g of oats every day can reduce the total cholesterol by 30%. British medical scientists held the opinions that oats can lower the cholesterol level mainly because it contains a special type of soluble fiber and a variety of enzymes.

5. Fish Foods 

There is more than 1,500 species of marine fish in China. The fish has rich nutrition, suitable for middle-aged and elderly people. Canadian researchers conducted research on 70 elderly people (about 1/4 of them with AD) and showed that, the content of w-3 fatty acid in the blood of healthy elderly (especially docosahexaenoic acid, DHA) was far higher than that of elderly with dementia. DHA is rich in the deep sea fish oil and it can prevent heart diseases. Therefore, appropriately eating salmon can prevent dementia and heart diseases. Among the fats of fish, the unsaturated fatty acid is as high as 80 %, with long carbon chains. Therefore eating more fish oil has the function of lowering cholesterol, reducing atherosclerosis and vascular dementia. Fish is also rich in vitamin A, vitamin D, and vitamin B₁, vitamin B₂, vitamin B₁₂, etc..

6. Walnuts and other nuts food

Walnut, also known as Juglans, has high proportion of monounsaturated fatty oils (58% ~ 74%). It can increase nutrient supply to the brain. The trace elements and phospholipids can promote the nerve cell proliferation. The rich vitamin E has strong antioxidant effect. In addition, walnut kernel is used for “brain enhancement” in China for a long history, which is also very popular in Japan and some Southeast Asian countries.

7. Grape Wine

Grape wine contains glucose and fructose which can be directly absorbed in the body. Moreover, 1L grape win contains 5-7g organic acids, including lactic acid, acetic acid, etc.. These acids can stimulate the digestive system and enhance the appetite, help digestion and absorption of protein and vitamins, and possibly reduce the accumulation of cholesterol. Grape wine also contains calcium, magnesium, iron, sulfur, tannins, anthocyanins, etc. and all of them are beneficial to cerebral functions.      

8. Foods that may cause damage to brain memory 

A long time life practices and studies have shown that, many foods may cause damage to brain, which must be avoided. They are mainly divided into the following categories:

Excessive alcohol: various kinds of alcoholic beverages contain ethanol (alcohol). If excessive drinking, it can seriously cause damage to the brain and neural tissues, and neurological disorder and even dementia may occur. 

Saccharin and high-sugar foods: Saccharin is a kind of chemical product extracted from coal tar. It contains saccharin sodium, ammonia compounds, etc.. Frequently eating of them may cause paralysis and brain damage, etc.

Excessive sucrose intake may realize in vitamin B₁ deficiency and increased calcium consumption, which will reduce the essential nutrients for physiological activities of the brain, causing decline in human’s mentality. Therefore, sugar intake should be in accordance with the normal consumption. Moreover, the pure cane sugar contains no other nutrients, which is not recommended to excessive consumption.

Aluminum-containing foods and lead-containing foods: there is no excessive aluminum in our daily foods, but aluminum can be seen in some food additives, for example, household yeast, cheese and soda crackers. Although the content is low, elderly people should beware of that.  The leavening agents used in the production of some foods contain alum, for example, “old-fashioned” deep-fried dough sticks and cakes contain high content of aluminum, which cannot be excessively taken for a long time.  

Lead –containing foods are usually the foods processed through heated and pressurized puffing machine, including rice cakes and popcorn, etc. Since this kind of puffing machine contains a high content of lead, the lead content in the popcorn is often high, usually exceeding the allowable content. The lead will affect the human brain cells and nervous system after entering the human body, and even cause poisoning.  

Artificial colors and canned foods: Artificial colors and some canned foods contain preservatives. Taking them for a long time may impair intelligence and it should be aware of that.      

9. Nutrition and Composite Factors 

The integrated network effect of nutrients cannot be ignored. Professor Kamphuis explored the functional mechanism of a variety of nutrients of omega-3 fatty acids, B vitamins and antioxidants on the prevention and early treatment of senile dementia and published papers in 2010, suggesting that the combined effect of nutrients has regulating role in the cell membrane / synaptic degeneration, abnormal protein processing (amyloid β, Tau), vascular risk factors (hypertension , hypercholesterolemia ), inflammation and oxidative stress and plays a positive role in the early prevention and treatment of AD. This study also provided a theoretical basis for the research and development of nutritional products for the prevention of AD in the early stage. In 2013, studies (Nick van Wijk, et al) showed that, products containing the comprehensive nutritional formulations Souvenaid (containing uridine, docosahexaenoic acid , eicosapentaenoic acid , choline, lecithin, folic acid, vitamin B12, vitamins B6, C, E, selenium) are conducive to the memory improvement of patients with AD in the early stage.    

In summary, the prevention of AD need a long time of scientific and balanced diets. The weight of human brain is less than 1/40 of the total body weight, but its oxygen consumption accounts for 1/4 of the whole oxygen consumption; therefore, sufficient energy is the primary factor of brain health. Brainworkers may consume more energy. In the daily diets, the staple food intake should not be lower than the body’s demands, to meet the demand for carbohydrates. 

The demand of elderly for proteins is about 1g-1.2g/(kg body weight.d). If the supply of protein is inadequate, the tissue cells including brain cells may accelerate aging. The quantity and quality of protein are equally important. The components of the amino acids should be complete and the content of lecithin should be rich, so as to benefit the metabolism of the brain. 

Currently no exact and effective therapies for Alzheimer's disease are available. Reasonable diets may slow down the occurrence of the disease. It is feasible to balance the nutritional intake, take vegetable protein and calcium-containing foods, appropriately supplement vitamin E and lecithin, eat more fresh vegetables and fruits, reduce the aluminum, copper intake, eat less fat meat, and avoid excessive salts and sugars.      

II. Nutrition of AD patients

AD patients often have strong appetite in the early stage and they eat more each meal, easy to hunger, and gain weight. Sometimes, their blood glucose elevates and patients have insulin resistance syndrome; and with the increasing age, it may develop to diabetes. The early discovery and giving correct advices on nutrition can effectively avoid the concurrent chronic diseases.    

In the middle and advanced stages, the AD patients have decreased self-control ability in life and emotion, and they gradually become picky in foods, with anorexia, inattentive eating and paresthesia of tastes, which will affect the supply, absorption and utilization of energy and various kinds of nutrients. Critically ill patients often cannot take foods and swallow independently, which seriously affect the body's nutritional status. Weight loss and malnutrition are the common manifestation of AD patients, which will increase the burden on family care.

In summary, nutritional support plays an important role in the delayed occurrence and treatment of AD. A proper nutrition management is to maintain and improve the nutritional status of patients, improve the body’s immunity, reduce complications, lower the morbidity, and minimize the burden on the society and families.  

1. Assessment of patient’s intakes before nutritional therapy

Survey form of eating disorder 

After assessment, determine the diet principle and precautions according to the patient’s eating disorders. 

(1)    For patients who can automatically take foods, give a balanced diet.

(2)    For patients with bulimia, control the total calories, maintain a normal body weight and blood glucose, and appropriately take vegetables.

(3)    Diversify food production. Since the patient has poor memory, do not repeat the type of foods within a short time, to stimulate their appetite and prevent foods refusal.

(4)    Select the foods rich in iron, calcium, magnesium and potassium once or twice within one week. 

(5)    Containers that hold foods should adapt to the patient's preferences. 

(6)    The kernels of fruits must be removed. 

(7)    Patients difficult in swallowing should use the nasal homogenized meal or enteral nutrition.

(8)    Patients with gastrointestinal dysfunction can choose home enteral, parenteral nutritional support. 

2. Principle of nutritional therapy for AD patients  

The purpose of nutritional therapy for AD patients is to give reasonable diet supplement according to the extent of dementia and eating disorder, so as to retard the pathological process of dementia, and maintain the normal functions of body's organs and tissues as far as possible. 

(1)    Increase the protein supply: Guarantee the quality protein with high biological value. The high-quality animal protein should account for about 50% of the total protein. If the vegetarian diet is dominated, supplement the soybeans and their products, no less than 60g/day of protein. The foods rich in protein should be chopped and boiled soft, easily digested.  

(2)    Reduce the supply of fat and pure carbohydrates: The fat supply should be controlled at 20%～30% of the energy (50-60 g/day), including the oil and fat in the foods and cooking oil. Use the vegetable oils such as linoleic acid -rich soybean oil, corn oil, sesame oil rather than the animal fats. Increase the supply of olive oil, camellia oil and rapeseed oil which are rich in monounsaturated fatty acids. Appropriately increase the intake of w3 fatty acid -rich marine fish. The cholesterol content should be controlled within 300 mg per day. The intake of pure carbohydrates such as sucrose, fructose should be restricted.

(3)    Increase the intake of vitamins: Vitamin C and vitamin E are natural antioxidant , anti-aging protection agents. B vitamins are involved in the metabolism of three nutrients, and they are the coenzymes of a variety of important enzymes, which should be added for AD patients. Take more fresh vegetables and fruits, etc.. Supplement the trace elements such as iron, selenium, and zinc, etc. 

(4)    Others: Reduce the sodium salt intake and appropriately increase the supply of calcium and magnesium. Increase the frequency of meals, eating less each meal, not overeating. Strengthen the feeding for the patients who cannot eat independently, dominated by digestible liquid diet and semi- liquid diet, and even tube feeding.  

(5)    Food cooking should pay attention to color , smell, taste. Do not eat the fried and smoked foods; do not smoke and drink alcohol. 

(6)    Keep quiet when having a meal, since the noise will distract the patients. Turn off the radio or television when having dinner. The foods should be placed in a small bowl or saucer, one portion each time, to avoid more options for patients. With the decline in the social self-control, patients may take the foods of others and take non- edible things, deteriorated foods or drink harmful liquid, etc. Therefore, AD patients should be strictly monitored when having a meal. 

With the loss of feeling, patients’ perceptions of the world around them and the associated auditory, visual and tactile recognitions have been distorted, that is the cognitive disorder. Since the diets need foods taste and smell to induce appetite, patients with visual agnosia are unable to identify the foods, showing no eating. Another loss of feeling is that the patient cannot recognize the same color of foods, bowls and dishes; at this time, it is necessary to distinguish them using different colors of bowls and dishes. Sometimes, patients cannot use the tableware, but they can complete eating by mimicking the behaviors of staff and caregivers.  

(7)    Disability in movement often occur in the disease process. Some patients should be guided at the time of eating, and they then complete the whole process of eating according to the language prompts. Once their movement activity declines, patients may be able to use the spoon only. Patients with severe disabilities may lose their body weight due to inadequate intake of foods. In addition, the patient’s regular exercise capacity should be evaluated. Patients who have no difficulty in chewing or swallowing can take small strip of foods. If patients can eat large pieces of food, they need not the small strip of foods. With the disease progression to the end-stage, patients often cannot swallow and aspiration should be prevented. When having feeding disorders, patients should take more snacks many times and take high- nutrition foods and nutritional supplements against the decline in body weight.    

3. AD patients that need enteral nutritional support

AD patients may take in inadequate nutrients and increase the energy consumption (activity difficult to control). It is reported that the occurrence rate of malnutrition among AD patients is 66.7%. The disease state of a number of AD patients becomes deteriorated due to malnutrition and lack of care, which causes unnecessary hospitalization and the increased medical expenses of the whole society. In the early stage, AD patients may have fewer intakes of foods due to loss of taste, decreased ability of daily living, forgetting dining and emotional factor; in the advanced stage, the patients usually require EN due to difficulty in swallowing, refusal to eat and decreased awareness. The primary purpose of AD nutritional therapy is to reduce complications, improve quality of life and reduce mortality. If some AD patients cannot or are not willing to accept natural diets or their food intake is insufficient to meet the physiological needs, enteral nutrition support can be provided for them when gastrointestinal conditions permitted ^[1-3].    

These conditions may include:  

Persons who cannot swallow or difficult to swallow due to central nervous system disorders, loss of consciousness, loss of gag reflex and esophageal motility disorder, etc.. 

Persons with severe oral diseases, dental and periodontal disease who cannot chew; 

AD patients whose nutritional demand is increased but less intake, such as major surgery, severe infection, hyperthyroidism , cancer and chemotherapy / radiotherapy ;

Patients accompanied by gastrointestinal disorders who cannot absorb the natural foods, such as patients with inflammatory bowel disease , pancreatic disease , liver disease , malabsorption syndrome, or AD patient with functional dyspepsia, anorexia, etc.;

Patients combined with diabetes , COPD, renal disease , cardiovascular disease need the special disease -specific type enteral nutrition as an alternative to natural food as a nutritional supplement due to the impact of disease, combined with reduced gastrointestinal motility and dysfunction, etc.. 

In general, the indications for AD patients to select enteral nutrition can be appropriately expanded. Many patients can accept the enteral nutrition as nutritional supplement while taking in a small amount of natural foods, that is, the combination of “foods + enteral nutrition”. The enteral nutrition approaches include oral nutrition supplement (ONS), nasogastric (intestinal) tube, percutaneous endoscopic gastrostomy/jejunostomy (PEG/J) and percutaneous puncture stoma jejunum, etc..  

4. Selection of enteral nutrition for AD patients

The enteral nutrition solution selected should be refined chemical elemental diet or liquid elemental diet that are easily digested or absorbed, and then gradually to enteral nutrition solution with the entire protein as nitrogen source. It is unnecessary to use “one kind” enteral nutritional formulation all the time. For some AD patients with combined diabetes, COPD, renal dysfunction, liver dysfunction, the disease-specific type preparations should be used. Taking the AD patients with diabetes mellitus as an example, they should accept the diabetes-specific formulations as the enteral nutrition support, with low energy density (0.75-0.9Kcal/ml), high heat production rate of monounsaturated fatty acid, using the polysaccharides (e.g., tapioca starch, etc.) as the main source of carbohydrates, containing the soluble dietary fiber. The addition and use of special nutrients such as glutamine, arginine, n-3 polyunsaturated fatty acids, soluble dietary fiber and medium chain triglycerides (MCT) should be noted.   

5. Enteral nutrition for AD patients and prevention and treatment of complications   

For AD patients with a long-term fasting, severe gastric motility disorder, slow or poor recovery of gastrointestinal functions after trauma or major surgery, the start time and induction time of enteral nutrition support can be appropriately extended, for example, five days or longer. The parenteral nutrition should be supported and supplemented in the induction process, that is, gradual transition from parenteral nutrition to enteral nutrition. 

During the transition process, gastrointestinal instillation or pumping is carried out for 24 hours. The preparations should be based on elemental diet or oligopeptide-type whole protein enteral nutrition, starting at 10-25ml / h. It will spend 3-6 days to the full amount. For elderly patients, enteral nutrition infusion is realized through infusion pump. Generally the enteral nutrition is not required to be prepared, which can be used up on the day when opened. Keep the temperature in the enteral nutrition infusion process. If the temperature is too low, the phenomenon of intolerance may appear, such as abdominal pain, diarrhea, etc. ; generally the temperature should not be too high, which is easy to cause deterioration. 

Infusing other drugs from the feeding tube should avoided, especially drugs that may have stimulation to gastrointestinal tract, to reduce irritation of the gastrointestinal tract and prevent dysbacteriosis. 

Requirements for enteral nutrition feeding tube for AD patients: the tube diameter should be less than 2-3 mm; if the tube diameter is too large, nose, stomach, esophageal compression symptoms easily occur. The tube diameter should be selected according to specific condition of patients. 

For AD patients with a long-term catheterization, nasogastric feeding tube should be regularly replaced. The nasogastric feeding tube should alternatively inserted to two noses, to prevent nasopharynx ulcers, gastric erosion and esophageal damage caused by a long time of stimulation and compression. The gastric residual liquid should be regularly checked, the urine, blood sugar and blood biochemical indexes, body weight, blood routine tests including lymphocyte count, serum albumin, prealbumin should be monitored. If the gastric residual liquid is too excessive (> = 100ml), reduce the supply and slow down the rate of supply, etc..   

The common complications of enteral nutrition for AD patients are basically the same as the young adult, such as bloating, diarrhea, abdominal pain, gastric retention, nausea, vomiting, aspiration, nasopharyngeal ulceration, luminal blockage, hyperglycemia, hypoglycemia, hyperammonemia psychosis, but the incidence is higher than that for young adults, which should be particularly noted. 

It should be particularly noted that, AD patients are often in lethargy and coma state, lost of swallowing function and their pharyngeal sensation becomes not acute, unable to swallow the gastrointestinal liquid reflux to the mouth but inhalation to the trachea, causing lung damage. The elderly patients with dementia accompanied by gastroesophageal reflux disease are more susceptible to aspiration pneumonia. When the patient inhales the gastrointestinal secretion containing enteral nutrition liquid, it will produce strong chemical stimulation on the tracheal and lung tissues due to the low pH in the enteral nutrition, which will result in a secondary infection and form pneumonia, reduce the alveolar ability of oxygen exchange, weaken the ability of patients to clear away bronchial secretions, forming a vicious cycle; if not handled timely, it will affect the lives of patients.

Many approaches can prevent the occurrence of aspiration pneumonia, including: ① place the patients in semi-recumbent position for enteral nutrition infusion ; ② regularly inspect the gastric retention, and when necessary, stop the influsion of nutrient solution or slow down the rate; ③ when the respiratory tract has lesion, consider jejunostomy, and then enteral nutritional support; ④ when necessary, select the nutrient solution with low osmolarity. Once the aspiration phenomenon occurs, immediately discontinue the enteral nutrition and remove the gastric contents; immediately suck out the liquid or food particles from the trachea. Even a small amount of aspiration, cough is encouraged to remove the particles in the trachea. If the food particles enter the trachea, perform bronchoscopy immediately and remove all food particles. Intravenous infusion should be performed to eliminate pulmonary edema; use appropriate amount of antibiotics to treat the lung infection.  

6. Parenteral nutrition for AD patients 

The elderly AD patients who cannot receive the enteral nutrition due to gastrointestinal dysfunction, gastrointestinal obstruction, bleeding, severe intestinal absorption dysfunction, severe diarrhea, persistent vomiting, severe acute pancreatitis, can receive the parenteral nutrition support. For parenteral nutrition, it is necessary to adopt the ultimate filter to reduce the incidence of sepsis or bacteremia. 

Infusion pumps should be used. The pumps with microcomputer control are provided with the bubbles or alarms. The flow rate of pumps should be calibrated regularly. 

Peripherally inserted central catheter (PICC) is to insert the catheter from the cephalic vein or basilic vein of antecubital fossa to the central vein using sterilization technique. It has minor side effect and can effectively prevent the occurrence of hemothorax and pneumothorax.

Home parenteral nutrition support has a special significance for AD patients. Home parenteral nutrition support is an improvement on the basis of modern parenteral nutrition support technology and a significant development in clinical applications. A safe home parenteral nutrition support is completed jointly by medical staff, patients and family members.

AD patients can receive the home parenteral nutrition support. Its indications are basically similar to those of parenteral nutrition support in hospital, but more consideration should be given to its safety and effectiveness, for a long-term application. However, considering the complexity of formulations and configuration, experienced nurses / doctors / pharmacists / nutritionist should work together to guarantee the safety and effectiveness ^[4].        

III. Expert Consensus on Parenteral and Enteral Nutrition Therapy for AD Patients    

The diet and nutritional status of AD patients in the early stage in community and the paired control group were analyzed and compared (Bryna Shatenstein, et al). Results showed that, the dietary intake of nutrients for AD patients (including carbohydrates, trace elements, fatty acids, etc.) was significantly lower than that of the control group ^[3] .  An open trial for a period of 12 months showed that, for the early stage of AD patients, the use of vitamin and nutrient compounds can improve the patient’s cognitive functions; however, the use of the same vitamin and nutrient compounds can delay the disease progression, rather than improve the patient’s cognitive functions^[4] .Thirty-five patients with mild dementia were given antidepressants, cholinesterase inhibitors, and vitamin supplements (including multivitamins, vitamin E, α- lipoic acid ) and encouraged to improve the diet and lifestyle (Bragin V), and results showed that, it not only delayed the disease progression, but also improved the cognitive functions, especially the memory and prefrontal function^[5]. Weight loss is a common complication of AD. A four-year follow-up survey on 440 AD patients in the community showed that, 87 patients lost their body weight by more than 4% in the first year of follow-up, and such weight loss can be used as an important factor to predict cognitive decline rate of patients^[6] .  In recent years, one randomized, controlled study was performed. Ninety –one AD patients identified with risk of malnutrition by MNA were randomly assigned to intervention group that received three- month ONS and the control group that only received the conventional treatment.  Three months later, the body weight in the intervention group was significantly enhanced and such improvement of nutritional status can last until 3 months after discontinuance of ONS, however, the patient’s cognitive function was not improved significantly^[7].    

A survey on inpatients in the United States revealed that, among 186,835 patients with severe dementia, 34% of them used NGT or PEG ^[8] . In a prospective cohort study in Israel for a period of 17 months, 62 hospitalized patients with cognitive disorders among 88 received the tube feeding, and 26 patients did not receive tube feeding. The indications of tube feeding included dysphagia, refusal to eat, and decline in consciousness, etc. Results showed that, in the tube feeding group, 21% patients had bedsores, while the 42% patients had bedsores in the non-tube feeding group. The mean survival time of the tube feeding group was 250 days, while that of the non- feeding group was 40 days^[9]. Till now, cohort studies of EN on prolonging the life of AD patients, enhancing the quality of life, improving the physical functions and reducing the incidence of bedsore and other complications have not reached consistent conclusions ^[9-12].  Nevertheless, many researchers believe that, every patient diagnosed with AD should receive nutritional status assessment and monitoring of body weight to prevent dehydration. AD patients in the early stage should be given ONS when they are found to have malnutrition risk ^[13].  Although the benefit of EN is not clear, among the patients with advanced AD, EN is still a feasible measure for those who refuse to eat and have difficulty in swallowing ^[2].  It is a complex issue to decide when to use EN, which will involve in the awareness of medical staff and clinical needs and ethics, the future goal and care plan, etc. ^[14] .

IV. Recommendations 

1.      AD patients have malnutrition risks. Each AD patient diagnosed with AD should receive the nutritional status assessment, especially the weight monitoring (D).

2.      Comprehensive diet and improving lifestyle, multivitamin supplement, application of combined antidepressants and cholinesterase inhibitors may improve cognitive functions of AD patients in early stage (C).

3.      AD patients should be given ONS when they are found to have malnutrition risk in the early stage, including additional oral nutritional formulation (B) and daily diets.

4.      AD patients in advanced stage who cannot eat can receive the tube feeding depending on the particular circumstances, and if condition permitted, perform PEG (B).

Chen Wei

References  

1.      Wei JM, Elderly Clinical Nutrition. Beijing: People's Health Publishing House, 2011.212-215 

2.      2．  Finucane, T.E., C. Christmas, and K. Travis, Tube feeding in patients with advanced dementia: a review of the evidence. JAMA, 1999. 282(14): p. 1365-70.

3.      Shatenstein, B., M.J. Kergoat, and I. Reid, Poor nutrient intakes during 1-year follow-up with community-dwelling older adults with early-stage Alzheimer dementia compared to cognitively intact matched controls. J Am Diet Assoc, 2007. 107(12): p. 2091-9.

4.      Chan, A., et al., Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Other Demen, 2008. 23(6): p. 571-85.

5.      Remington, R., et al., Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen, 2009. 24(1): p. 27-33.

6.      Bragin, V., et al., Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen, 2005. 20(1): p. 21-6.

7.      Soto ME, et al., Weight loss and rapid cognitive decline in community-dwelling patients with Alzheimer's disease. J Alzheimers Dis, 2012. 28(3): p. 647-54.

8.      Lauque S, et al., Improvement of weight and fat-free mass with oral nutritional supplementation in patients with Alzheimer's disease at risk of malnutrition: A prospective randomized study. Journal of the American Geriatrics Society, 2004. 52(10): p. 1702-1707.

9.      Jaul E, Singer P, Calderon-Margalit R. Tube feeding in the demented elderly with severe disabilities. Isr Med Assoc J, 2006. 8(12): p. 870-4.

10.   Mitchell, S.L., et al., Clinical and organizational factors associated with feeding tube use among nursing home residents with advanced cognitive impairment. Jama-Journal of the American Medical Association, 2003. 290(1): p. 73-80.

11.   Nair, S., H. Hertan, and C.S. Pitchumoni, Hypoalbuminemia is a poor predictor of survival after percutaneous endoscopic gastrostomy in elderly patients with dementia. American Journal of Gastroenterology, 2000. 95(1): p. 133-136.

12.   Alvarez-Fernandez, B., et al., Survival of a cohort of elderly patients with advanced dementia: nasogastric tube feeding as a risk factor for mortality. International Journal of Geriatric Psychiatry, 2005. 20(4): p. 363-370.

13.   Belmin, J., Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease: a consensus from appropriateness ratings of a large expert panel. J Nutr Health Aging, 2007. 11(1): p. 33-7

14.   Shea T.B, et al, Nuetrition and Dementia : Are weking the  Right Questiong ?  Journal of Alzheimer’s Disease, 30(2012) p 27-33

15.   Patrick J.G.H. Kamphuisa，Philip Scheltens. Can Nutrients Prevent or Delay Onset of Alzheimer’s Disease? Journal of Alzheimer’s Disease 20 (2010) p 765–775

16.   Nick van Wijka,Laus M. Broersena,Martijn C. de Wildea,et al.Targeting synaptic dysfunction in Alzheimer’s disease by administering a specific nutrient combination.

17.   Philip Scheltensa, Jos W.R. Twiskb, Rafael Blesac. Efficacy of Souvenaid in Mild Alzheimer’s Disease: Results from a Randomized,Controlled Trial. Journal of Alzheimer’s Disease 31 (2012) 225–236

Section 5 Cognitive Training and Functional Rehabilitation Training for Alzheimer Disease

I. General introduction of cognitive training and functional rehabilitation training

Alzheimer disease treatment should include two aspects, namely, drug therapy and non-drug therapy. Non-drug therapy plays an important role in the management of dementia. The non-drug therapy for Alzheimer disease can be described as a vertical integrated treatment for patients, which includes cognitive treatment, functional training, mood maintaining, psychological intervention, psychological counseling, legal issues, environmental intervention, nutrition supporting, behavior treatment, entertainment and life nursing and other treatments and interventions[1a]. Non-drug therapy is based on the cognitive neuropsychology.

The fundamental theory of cognitive neuroscience is the nature of intelligence and the origin of consciousness [1]. As the basic cognitive process of the intelligence, it includes sense perception, attention, memory, language, thought and consciousness. With the patients of cognitive impairment as the research object, cognitive neuropsychology usually apply the method of case study, with the help of specific relevance and separation model of the patients, to explore the impairment or retention of the patients’ cognitive function, so as to speculate the cognitive mechanism of the normal people as well as discuss the functional organization of the brain.

It provides theoretical basis for diagnosis, rehabilitation and treatment of diseases in clinical practices. Compared with traditional neural psychology, cognitive neuropsychology emphasizes the case study on methodology. As a scientific and effective method, case study has important significance in guiding rehabilitation,for instance, traditional neuropsychological rehabilitation focuses on groups training, with fixed rehabilitation method, and patients of the different types tend to accept the same rehabilitation treatment, so the effect is not ideal as a result of lack of pertinence; while cognitive neuropsychological rehabilitation focuses on the analysis of cognitive dysfunction of specific cases, and the corresponding rehabilitation training, which can focus on the key points and provide more effective strategies for senior functional rehabilitation so as to achieve twofold results with half the effort.

The treatment goal for Alzheimer Disease is not just a maximum relief of the cognitive decline associated with disease progression; even more important is the maintaining of daily life ability of the patients. The goal aims to slow down of the AD symptoms and maintain the daily life ability of the patients, which is actually a relief of symptoms for patients and caregivers. Treatment can also delay the time for patients to get access to care organizations and reduce their degree of dependence on caregivers. The overall goal of the care rehabilitation for dementia patients: maintain the patient's adaptation level; adjust the environment pressure, to make it consistent with the ability of the patient's life. The principle of rehabilitation nursing: (1) maintain structure, order and mode;(2) try to avoid changes, if the changes are necessary, carry out the changes in incremental method;(3) give full play to ability: ability is associated with the health of the whole body, so the clarification and treatment of each coexisting disease, acute or chronic, is very important for maintaining the ability. (4) Rely on habit and patients’ preferences. 在康复治疗中，要注重要点，简化任务，在患者最易获得合作的时间进行训练[2]。

 “Cognitive training” includes the training on memory, attention, orientation, thinking, executive function, problem solving skills,language and language use, etc. The design of the training aims to improve cognitive function, regardless of any non-pharmaceutical interventions in the mechanism. Typical cognitive training focuses on specific areas of cognitive function (such as memory, attention, and problem solving skills), but the more common cognitive trainings are dealing with the cognitive mediated areas in daily life functions (such as daily life ability, instrumental daily life ability, social skills and behavior disorder), and cognitive training can also be targeted. The reality orientation training can improve the cognitive function of AD. Integrity - promoting nursing process treatment can improve the short-term memory and visual perception of AD. 3R intelligence activation method: 1R: Reminiscence: Stimulate the memories by recalling the past incidents and related objects; 2R: Reality orientation: Stimulate the memories related to its time, place, characters, environment of AD patients; 3R: Remotivation: Stimulate the patients’ mental and cognitive ability by discussing, thinking and reasoning. The maximum effect of the training can be reflected in the improvement in learning, memory, executive function, daily life ability, overall cognition, depression and overall function [3,3a].

It is now believed that mental stimulation and social interaction could help to build cognitive reserve. Some recent studies have found that the stimulation concerning mental, physical and social activities can provide some protection to prevent dementia respectively, and the stimulation with the integration of two or three kinds of activities will bring the greatest benefits. Cognitive dysfunction analysis on specific and individual case and the corresponding brain function rehabilitation training can provide more effective strategies for the recovery of advanced brain function, so as to achieve twofold results with half the effort.

Carrying out the training of improving cognitive or perceptual cognition function in the elderly persons can yield benefits. Recent neuroscience researches have proved that neural plasticity still exists in the brain of the elderly persons, so brain training as an effective process, can serve as a useful way to build a compensating circuits and restore the ability which has been lost. So far, the largest randomized trial (ACTIVE research), involving 2802 old people in the United States, randomly divided into 3 training groups and a control group to compare the effects on three training programs (memory strategy, reasoning, and speed of processing), which collected the measurement results immediately after the training and 1- 2 years of follow-up. Results have shown that the training in the special fields contributed to the improvement of the targeted cognitive function. Compared with the reasoning and memory training strategy with paper and pencil training, the targeted training based on the speed of the computer has yield the biggest benefit [4]. The patients with mild cognitive impairment has achieved limited effect when receiving the single memory strategy training [5]; Adopt the TNP computer software, and carry out the cognitive function training involving many fields with a complex model, which realized in the lasting positive impact on memory, and the accompanied symptoms such as depression, behavior and nervous disorders can also get better [6]. The effect of cognitive function training in multiple areas on general cognitive and function of patients with AD has also been confirmed [7].

II. Cognitive Training

(1)Memory training

1. The definition and classification of memory [8]
Memory refers to the nerve process of storing and extraction of the acquired information or experiences in brain. Human memory is quite complex cognitive function, which can be divided into three independent but interactive basic processes namely coding, storage and extraction, and the idea or concept in this process has made major contribution to the memory studies of cognitive psychology.

Memory can be divided into short-term memory and long-term memory. Short-term memory: (1) video memory; (2) immediate memory; (3) primary memory (primary memory); (4) working memory. They are four different types, among which the working memory is a concept of a short-term memory put forward from the point view of cognitive psychology, a term used to describe the processing and storage of temporary information. Long-term memory refers to the situation that information can be stored in the brain for more than 1 minute, which can be divided into declarative memory or explicit memory and non declarative memory or implicit memory. Declarative memory includes semantic memory and episodic memory, among which semantic memory contains all the information concerning the language used by people and episodic memory is the memory of personal experience. AD patients suffered the loss of episodic memory in early stage.

Learning can enhance synaptic plasticity and form the new neural circuits, that is to say, the change of the synaptic plasticity and the formation of new neural circuits should be the neural basis of memory. The synaptic plasticity can be improved by constant learning of new things and consolidating the learned things on the basis of maintaining active learning and memory function.

2. The strategies and methods of memory rehabilitation

(1)  Rehabilitation by using residues of explicit memory [9]

Mnemonic method: [10, 11]

Association method: patients should associate in mind the information for memorizing with the familiar food, which is also known as correlation method. For example: Name association method: use a color portrait photo as the stimulation object, and the people in the photo should have contact with the patient, but the patient can't remember his or her name. The name in the photo should be described with visual images for association, and these descriptions can provide a hearing association through the name and the associated objects and activities. Then test and train the patient. Face and name association method: first of all, the patient should be asked to associate the man with appearance characteristics in mind with an acquaintance or a celebrity.  The figure should be presented by computer, and read the name by the sound. The portrait should be presented again to the patient 20 minutes later without the name of the figure. And ask the patient to input the name of the portrait he or she can see. If the patient input the wrong name, he or she can have some hints. [9].

Image method: It is also known as visual inclination, by visualizing the words or concepts for learning into images, which can helps to remember the names of strangers. For example: Images stimulation method: A series of images involving 2-6 words should be presented to the patients in the training, with each word lasting 1-14 s, and then one word should be took out, and the patients should be asked to point out the initial sequence number of the word. Every time training should begin with two words. When the trainee can get the score more than 90% in 3 consecutive days, one word can be added in the image in order to improve the difficulty of training process [9].

Story making-up method: the patient should be provided with the help to put the information for memorizing into a small story according to his or her own habits and hobby, and express the information through telling the story, so as to improve patient’s memory. For example: Funny story association method: it is also a kind of memory training. To show the method to the patient and the funny story containing 20 words should be presented by computer, and the patient should be asked to read the story and input the words he or she remembered. If he or she input the wrong word, hints should be provided [9].

Key word method: it also called initials combination method, if the patient wants to remember the event order or do many things at the same time, the first letter or word of each thing can be linked together to memorize.

Recitation method: recite the information for memorizing loudly or quietly and strengthen the memory by repeating the information.

Prompting method: provide verbal or visual cues.

Flashbacks method: think back each step of the events to find the missing items or recall something.

Digital segmentation method: effectively help memorize numbers, for example, when memorizing the telephone number 13547985357, it can be divided into 1354, 7985, 357.

(2) Rehabilitation by using relatively complete system of implicit memory [9]
It is now believed that the memory impairment of AD patients and psychiatric patients mainly refers to explicit memory, and partial implicit memory can be relatively retained. Therefore, rehabilitation measures based on implicit memory might achieve better treatment effect than those based on the explicit memory.

Errorless learning method: The rehabilitation principle of a so-called “errorless learning" could be applied in the memory rehabilitation for psychiatric patient.  This method was developed by the method of training animals; its principle is a kind of rehabilitation technology eliminating incorrect response in learning; it aims to avoid the mistakes in learning, promote the improvement of the cognitive function. Mistakes should be avoided in the learning. Results have suggested that the psychiatric patients suffered from memory impairment have achieved great improvement in memory after receiving the errorless learning method in training, and the reason is that the memory impairment of psychiatric patients mainly refers to explicit memory, and partial implicit memory can be relatively retained. On the other hand, after repeated failures, patients are easy to lose confidence, which is not conducive to the improvement of the training effect for the patients [9].

Other rehabilitation trainings involving the implicit memory: It consists of 20 basic daily activities, such as: wash face, brush your teeth, prepare coffee, put the items in the right place, turn on and off the lights, send cards, read a short sentence, pay the cheque, shopping with a list, etc. Those trainings has shown that the activities in which the implicit memory plays an important role can exert an effective impact on the rehabilitation training for the mild and moderate AD patients.

For memory disorders in AD patients, the trainer should depend on the patient's preferences, habits. Because most fixed or habitual behavior is based on program memory, excessive helps will accelerate the loss of habitual or procedure behavior ability for AD patients. The trainer should know exactly what kind of help the patients need. The help provided for the patients should be a continuous incremental process, from "reminding" to "auxiliary" to "do with him” and to "do for him”. When it comes to the rehabilitation training for amnesia patients, images, lights or words can be used as a mark in places like washroom, dining-room to remind the patient, or the patient's name, address, telephone number can be written on the note to put in the patients’ pocket. The patients should be trained to exercise the brain continuously in order to improve the memory. Caregivers need to consciously train the patients to timely review the contents of memory again and again to strengthen the memory ability, which is very important for improving memory, slowing the decay and the disease development.

(3)Rehabilitation therapy by using external memory aids[9]

Electronic memory aids, voice organizer and other electronic tools can timely remind patients of matters that need to be done or have been forgotten; some of new electronic locators can make positioning for patients in a timely manner to prevent them from being lost. If a patient has been diagnosed with dementia, his/her caregiver should carry relevant data about him/her: such as the patient's name, home address, telephone number, his/her contacts’ telephone number and some suggestive identification cards.

Traditional external memory aids [9]: external memory aid is a kind of tool which helps patients with memory disorder by auxiliary aids or prompts outside human body. Common external auxiliary tools include diary, activity agenda, map / drawing, which apply to the disabled in terms of time and spatial orientation; Memory prompt tools include detailed list, tape recorder, label and so on, this method applies to young patients who a have mild cognitive disorder and minor other cognitive disorders, these memory aids are effective for functional dysmnesia.

The following introduces two different training methods: diary only (DO) and diary and self instructional training (DSIT). DO is a model based on neuropsychological therapy, which focuses on the development of patients’ functional technique, the trainee learn a kind of behavioral order and obtain the required information by taking diaries, it is often used in rehabilitation therapy. DSIT emphasizes on training patients’ ability of self-regulation and self-awareness. The patients shall be asked to carry out the following self-directed training strategy: W - What are you going to do; S - Select a strategy for the task; T - Try this strategy; C - Check how this strategy functions. These steps are abbreviated as WSTC, which provides the trainees with a systematic approach on how to use diaries to compensate for memory.

Electronic memory aids[9]

Electronic memory aid - NeuroPage: for patients with memory impairment, external auxiliary equipments may be a kind of better memory compensation strategy in a way. It is a simple and easy-to-use radio paging system, for example, if a patient does not know today's date, the pager may send the following information:. "Good morning, today is November 21, Monday."

This particular paging system can significantly improve daily memory of patients with brain trauma.

Voice Organizer (another electronic memory aid): it is a kind of handheld dictaphone, which can identify patients’ language mode, store oral instructions of users and orally set playback time for these information. When it is time for playback, it will beep. By press the button, the information can be displayed. Voice Organizer is superior to traditional memory aids in terms of convenience and high efficiency in use.

Non one-to-one computerized training is the trend, which not only takes the advantage of multimedia but also effectively saves health care resources. YWG neuropsychological training system of Professor Yin Wengang involves training projects related to memory: graphic memory training, Chinese character memory training, spatial memory training and etc., which can be a good try.

(4) Other rehabilitation methods for memory disorder[9]

Two types of memory training can be carried out respectively on patients: prospective memory training and retrospective memory training. The former is to let patients complete assigned actions at specific time, while the latter requires patients to recall their previous behavior. For example:

There is a kind of game called Bingo, as a cognitive stimulation, it has good influence on short-term memory, word memory and word recognition.

Transcutaneous electrical nerve stimulation therapy can improve patients’ long-term memory on language, compared with the control group, fluency of language is improved.

Memory training can help patients remember the living environment, people around, domestic and international events recently occurred, for example, let patients watch TV news and then ask questions about contents of the news, you can ask frequently and then let them answer.

Learning of written materials mainly adopts PQRST method:

P (preparation): prepare contents to be remembered;

Q (question): ask yourself questions related to problems;

R (read): read data carefully so as to answer questions;

S (state): make repeated statement on data read;

T (test): test your own memory by answering questions.

(5)Environmental adaptation

Environmental arrangement: affix labels on the wall, or classify various items, or place according to fixed positioning rules, and etc.

Transform household articles or the environment: such as using timing electric lights, electric kettle, tying keys on the belt with a chain.

(6)Provide patients with tips and clues [9,12,13]

Write down some tips and post them at important places where patients can easily see, and the tips should be brief, clear and have highlighted key points. For example, mark with pictures, lights or words at washing rooms, restaurants so as to alert patients, can write down patients’ name, address, telephone numbers on a slip of paper and then put it in their pockets. In order to enhance patients’ memory, you may help them recall some important events, such as children’ marriage anniversaries, birthdays and so on. Strengthen the training of patients constantly on using brain so as to improve memory. Caregivers need train the patients consciously, review memory contents timely and make strengthening repeatedly, which are very crucial for improving memory, slowing down recession and aggravation of diseases.

(7)Recalling therapy[9,12,13]

In order to improve patients’ memory, recalling therapy can be carried out. Let patients recall their past so as to strengthen memory. For example, show meaningful photos (wedding photos, family portrait, etc.) repeatedly to patients; relate unforgettable sweet memories, which can improve the patients’ mood, calm agitated behaviors, improve the remaining memory function. In addition, give orientation and reinforce memory repeatedly (e.g. repeatedly train by emphasizing time, space and character), chat with patients about books, newspapers and magazines that they are interested in, let patients participate in simple puzzle games (such as simple jigsaw puzzle), all of these are helpful for the improvement of memory.

 (II) Cognitive training of thinking, reasoning, problem-solving

1.Reasoning training

Teaching strategy in searching mode, for example: search and identify the next one adjacent to the letters or words in a series (e.g. c, e, g, i ...) [14,15]

2.Information-processing training

(1)    Speed of processing training: visual search and divert attention, for example: after transitory appearance of an object on a computer screen, divert attention of the trainee, then ask him/her to confirm which object it is [16-18].

(2)    Other methods: interest, demonstration, reward, token, telephone conversation.

3.Thinking training

For example:(1) Read information from newspaper; (2) Sorting; (3) Classify: pictures, articles, etc.; (4)Training of problem-solving skill.

4.Thinking and memory training [12,13]

Let patients do some simple analysis, judgment, reasoning or calculation test, can ask them try to say something about an article or animal, for example, you can ask "what a dog can do?". Doing more training can improve thinking ability of the patients.

(1)    Cognitive training of amnesiac: image memory training of right brain.

(2)    Supplement (learn new things): Learn new information through classification or visual organization, ask questions or make graphical interpretation so as to train patients’ ability in concentrating on a thing and train their memory ability through environmental cues, notebooks and paper slips.

(3)    Recall (the past): Training patients to recall stories about old photos or old objects by watching them.

(4)    Funny riddles - train logical relations and flexibility of thinking: during training, give each patient 10 lantern riddles (close to life and interesting) and ask them to guess, three of the anagrams are to guess the instructions underneath, another three ones are to do body posture according to the words, these two kinds of riddles may be combined together for guess.

(5)    Story game: Training of memory, understanding and expression skills. Trainers tell a story or news, let patients repeat first and then summarize this story or news. Or trainers let patients read a story and then answer the questions raised by the trainers.

(6)    Graphic recognition and memory - training of the ability of analysis and synthesis: show three groups of similar pictures to each patient, then let them find differences between each group of pictures and make summary; present different graphics to patients and let them make classification; show patients their own old photos and let them tell stories about these photos.

(III) Attention training

Playing chess, folding paper and listening to music can be helpful for the training of attention. Both caregivers and family members should participate in the whole course of cognitive training, caregivers should learn how to arrange for patients’ practice in daily life, including technology-based training, information-processing training, and special training and so on.

1.Technology-based training

(1) Guessing game;(2) Deletion task; (3) Sense of time; (4) Computer-assisted method.

2.Special training

Mostly carry out through pen and paper, while completing exercises on paper, patients are asked to react to commands sent by a recorder or therapist, such as passing game.

(IV) Orientation training

Train caregivers how to arrange for training time, place and participants at home.

1.Reality Orientation: Help patients recognize and understand such information by using special skills or methods as date, time, place, people and so on. For example: Marking: by using special calendar (one page for each day), caregivers mark the matters that patients need to do daily or weekly and paste marks or photos on different places at home. Let patients go out, let them remember what they see and retell the process.

(V)Other cognitive training

1. Language training [19-21]

Severity of dementia is the most important factor affecting language barrier of AD patients. In the early stage, mild naming disorder, mild retelling disorder, listening comprehension and writing disorders have occurred among AD patients; language barrier shows fluent aphasia, similar to cortical sensory aphasia for AD patients in intermediate stage; transition from cortical sensory aphasia to Wernicke aphasia and eventually silence in the advanced stage of AD. Language barrier of patients with AD has its own characteristics, which is different from aphasia incurred by cerebral vascular disease and is only similar to fluent aphasia. Severity of aged dementia (AD) is the most important factor affecting language barrier of AD patients. Language change of AD patients in early stage can be used as one of basis for early diagnosis and differential diagnosis [19].

Language barrier of AD patients in each stage is represented by different forms of fluent aphasia; there are six cases that are similar to cortical sensory aphasia, five cases similar to Wernicke's aphasia, one case similar to anomic aphasia; severity of AD shows positive correlation with the range of brain atrophy [20].

(1)Specific implementation methods for language rehabilitation [2,12, 21]

Prior to treatment, therapist should conduct a detailed language evaluation so as to determine the type of aphasia, to find main aspects and the severity of the patient’s loss of linguistic function, and to identify the functions that the patient still possess so that the rehabilitation therapy is targeted and therapy with different degree of difficulty can be worked out. Therapy should first focus on the training of rehabilitation of oral language, center on speaking, spoken language frequently used in life (such as taking meal, drinking water, defecation, urination, sleeping, washing face, brushing teeth, taking medicine) should be used as emphasis. 

Direct stimulation: help patients restore the ability of daily expression through stimulation given by doctor, have them transform gradually from dependent passive speech to independent active speech.

Indirect therapy: let patients talk about their work, family, interests, hobbies, etc., have the dialogue focus on a topic and try to get rid of the difficulty in finding words so that the patients are easy to make expression

Other training such as training of computing power from easy to difficult, training of ability of spatial structure similar to playing building blocks.

Specific examples：

(1)    Training of listening comprehension: Therapist put pictures on a table, say the name of a word, then ask the patient to point out the corresponding one from the pictures. 

(2)    Name training: show a picture and then ask the patients to answer what it i

(3)    Retell: Let the patient repeat what the therapist said, take repeat training of the principle of no fatigue.

(4)    Reading comprehension: Ask the patient to read out sentences and articles, and explain the meaning or make corresponding choice by pictures. 

Caregivers should let patients read more books and newspapers, make more communication with them, can have the patients read newspapers or watch television and then retell the contents of newspapers or television, and make discussion on the contents; encourage the patients’ little progress in a timely manner so as to build up their confidence for rehabilitation. Communicate continuously with the patients through some small games so as to stimulate the patients and increase interestingness of the training.

(5)    Writing: Can start from copying, then gradually transfer to naming writing, dictation.

2. Therapy of agnosia [22]

Agnosia is a kind of disturbance of perception, mainly including visual agnosia, spatial agnosia.

(1)    Therapy of visual agnosia: for prosopagnosia, can let the patients remember their familiar relatives’ faces first, then repeatedly show photos of these relatives to the patients, later mix these photos with other photos and ask the patients to identify them.

(2)    Therapy of spacial agnosia

3. Therapy of apraxia [22]

At the time of training, therapist conduct training through slow and simple instructions on the principle from coarse to fine, from decomposed to coherent, from simple to complex. 

(1)    Training of structural apraxia: such as playing building blocks.

(2)    Training of apraxia of moveability: such as pouring water, making coffee.

(3)    Training of ideological apraxia: such as brushing teeth.

(4)    Training of ideological apraxia of moveability: for example, holding a toothbrush can prompt patients to brush their teeth.

III. Functional Training

(I) Training of life skills

Life skills generally include basic life skills, instrumental living skills and social skills. Training of basic life skills aims at cultivating patients' self-care ability: dressing, eating, toileting, etc.; Training of instrumental living skills is to train patients to do some simple household duties and to use electrical appliances, trainers make demonstration first, then let the patients imitate. Patients can do some other activities during the training till finally the patients can do these activities by themselves or operate by following the instructions. Allow patients to keep their own living habits such as same meal time or same cleaning habits as their past. Help the patients maintain their living ability as long as possible [2,9].

(II) Care of daily life and behavioral intervention

Quiet room, soft voice, mild white light, avoid noise and chaos. Control noise, cultivate plants and raise animals, live at places with appropriate temperature changes, avoid too much / little stimulation. Keep patients’ past living habits. Basic care: talk with patients slowly and gently by using simple words and corresponding gestures.

Behaviors of patients with AD are different from that of the normal, which are unpredictable, such as unusual dressing, rude behavior, disturbing others. The method for intervention is first to understand what the patients do not want to do, then guide them to change their behaviors and divert their attention by encouraging or deceit with enthusiastic attitude instead of command and isolation. Thirdly, provide a safe, quiet and familiar environment. Finally, encourage their good behaviors and give praise or reward [2,9].

(1)    Mild AD

 Arrange for activities and follow schedules strictly; arrange care programs for AD patients.

(2)    Moderate AD

Treatment of skin, nails, beard, table and chair and sleep care; accident prevention measures.

(3)    Severe AD

Basic nursing of oral cavity and perineum, prevention of bedsore; accident prevention measures.

(III) Financing ability

Train patients to simulate procurement, accounting, currency exchange, make shopping lists, write IOUs, write checks, make financial plans and so on.

(IV) Recreational activities and outdoor activities

Recreational activities can provide patients with a relaxed environment for living, expressing feelings and participating in social activities. Patients can obtain self-gratification through recreational activities. These activities can provide multi-sensory intervention therapy, including: art therapy, musicotherapy, pet therapy, aromatic plant therapy, lucotherapy, chiropractic, most of them are lack of insufficient evidence [3,23]

All the activities must be premised on patients’ own wishes and should not cause their dislike. Caregivers should guide the patients with an appreciative attitude, give them encouragement and praise.

Tell patients that they can participate in outdoor activities; caregivers should frequently arrange for these activities and encourage the patients to participate, train the patients to do activities they are good at, such as playing chess, playing balls.

(V) Social Activities

Respect patients, often extend greeting to them, talk with them about their feelings, help organize some social activities, for example: listening to music, let patients choose music by themselves, music can help patients keep quiet and improve their cognitive function; singing and playing games with others (including games that may be associated with real life: such as handling of emergency situation); create a similar environment at the patients’ home to reduce their sense of tension [9].

Wang Yinhua¹ Zhang Zhenxin²

¹Department of Neurology, First Hospital of Peking University

²Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Beijing Brain Health Center

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Section 6 Treatment of behavioral psychological symptoms (BPSD) in dementia patients

International Psychogeriatric Association (IPA) developed a term, named behavioral and psychological symptoms of dementia (BPSD) in 1996, which refers to symptoms of dementia patients such as disturbances in perception, thought, mood or behavior. There are two specific reasons to discuss these symptoms separately, on one hand, BPSD is the most serious damage factor for the life quality of dementia patients and their family, as well as the main issue for clinicians in the diagnosis and treatment of dementia patients; on the other hand, BPSD can be controlled by appropriate psychiatric intervention and treatment, thereby could greatly improve the life quality of dementia patients and their family.

For the treatment of dementia, especially the most representative one, Alzheimer's disease, there are no particularly effective treatments to date. Generally, there are two main categories for the treatment of dementia, pharmacological treatment and non-pharmacological treatment. Pharmacological treatment includes nootropic treatment in the improvement of cognitive symptoms as well as the management of BPSD.

Common behavioral and psychological symptoms associated with dementia

Common behavioral and psychological symptoms associated with dementia include hallucination, delusion, misrecognition, depression-like behavior, mania-like behavior, agitation, aimless roaming, wandering, physical and verbal attack, crying, fecal and urinary incontinences, sleep disorders, etc.; incidences of all these symptoms at various stages of dementia are listed in the following table:

Four possible types of factors for BPSD:

(1) Environmental factors, including safety in patient’s living environmental, adequate light, temperature, and skills of caregiver, their service attitude, etc.;

(2) Patient's own disease factors, including the types of dementia, severity of disease, severity of neurofibrillary tangles, etc.;

(3) BPSD symptoms caused by cognitive impairment;

(4) Inappropriate intervention or pharmacological treatment of dementia, as well as the adverse reactions of drug, etc.

Basic principles for the treatment of BPSD:

For the treatment of BPSD, the following principle of ladder treatment should be adhered to:

Treatment step 1: life management and psychological support

Step 1 is the basis of all dementia treatments, including improving living conditions, strengthening patient’s daily care and training of living skills, as well as technical training and psychological support for caregivers in various aspects.

Psychological characteristics of dementia patients:

1. Personality change: the so-called personality refers to a person's general practice of daily interactions. For dementia patients, the earliest and most common psychological characteristic is the change in personality, which break the general mode. For example, generous people become stingy, optimistic people become depressed, cautious people become fearless, etc. These changes are often surprising, as if the patient becomes a totally different person. 

2. Selfish: most dementia patients will gradually appear to be more and more selfish, without any considerations for the others. They sometimes behave like children, eating on their own, keeping stuff firmly, and not allowing anyone to touch; they often blame the others for unfriendliness, or torture themselves, etc., however, they show indifference for their family. In fact, this can be explained that the social and moral values, as well as altruism, are acquired and formed after entering into adolescence stage. Therefore, when the elderly patients get dementia symptoms, these social and moral values are gradually damaged, and then they will appear to have selfish tendency.

3. Control by the instinct: with the aggravation of dementia and forgetting of ethical and legal values, their behaviors and activities will be controlled by the instinct, as exhibited by hyperactive in appetite, libido, etc. But this "hyperactivity" does not refer to any enhancement in their ability or function; on the contrary, they will show their instinctive desires arbitrarily, regardless of time and occasion, without any moral scruples. Any discouragement and punishment cannot change these behaviors. For instance, they just undress publicly in front of the opposite sex, eat certain foods they like without restraint but show no interests to those foods they do not like.

4. Lack of self-knowledge: Because of hypofunction in the brain, patients are not aware of change in their performance and personality due to disease; therefore, it is impossible for them control themselves and revise it, let alone initiative for seeking treatment. Even being pointed out, patients will not believe they have a problem (given admitted at that time, it will be forgotten within a moment).

5. Nervousness: due to memory decline, the originally familiar environment and family will become completely strange to patients. Their behaviors will be nervous, keeping alert to everything around, or in a constant state of confusion and fear all the time.

6. Aggression: elderly dementia patients tend to be offensive verbally and behaviorally. In the eyes of others, patients will abuse or hit the others around them, for no reason, with an unexpected attack that people have no chance to avoid. There is no particular object to attack; anyone around the patients may become an object of attack.

7. Indifference: at the advanced stage of dementia, the memory in patient’s brain will become blank, as if being wiped off by an eraser; any meaningful thoughts and mental activities do not exist. The patients often stay in bed all day, without any voluntary activities; they show no response to the external stimuli but a vacant.

Principles of psychotherapy for patients with dementia

1. Limited objectives:

The goals of psychotherapy for elderly patients are different from young ones; for the youth, the treatment focus is to help grow and improve their personality, however, for dementia patients, this goal is unachievable. On one hand, during the decades of life, their personality development has already been basically finalized, leaving no room to change. On the other hand, because of the disease, patient’s brain is not able to dig and explore their own behaviors and inner heart; in addition, in terms of time, there is no opportunity for the therapists to slowly fix up the problems. Therefore, for dementia patients, psychotherapy should focus on their present to solve their practical problems, to help them do adapt to their current life and find happiness; all these are the treatment goals of psychotherapy.

2. Family participation

Family participation is crucial for the psychotherapy of dementia patients. Many patients and their family do not understand their sufferings from the disease; they are not able to treat patients in the right way, leading to the aggravation of the disease, with severe hostile tendencies among the patients. Therefore, clinicians need to provide an appropriate education to the family during the treatment, to have their family involved in the treatment, for improving communication among family members, as well as the environmental support from the society. In addition, as the family of dementia patients, they have to face a lot of problems and pressures, for which helpful advice from clinicians will be beneficial to them.

3. Patience

Due to the decline of comprehension and memory, dementia patients are slow in reaction when receiving guidance, or even stagnant because of forgetting the requirements from caregivers. Therefore, caregivers should be more patience, giving more time and instruction repeatedly in calm, hence to obtain better effects, although sometimes, it requires dozens, hundreds or even thousands of guidance and training.

4. To be simple

Life is complicated, therefore, do not try to ask the patients to complete complex tasks such as cooking, using washing machines, etc., which will only add their feeling of frustration, bringing unnecessary emotional response. Perhaps informing them where the toilet and where to go sleep is more important. Even in training patients to do those simple tasks, the procedures and steps should be minimized.

5. To provide appropriate support

Caring for dementia patients does not mean doing everything for them, which will only make their living skills decline rapidly; they should be encouraged to handle things within their capability. However, necessary assistance is required, because even doing their most familiar tasks, patients may be frustrated by the difficulties, which makes them retreat to avoid doing the tasks. Eventually, they will lose the capability of doing that particular task; at this time, appropriate assistance can prevent this from happening.

6. Patient-centered

In clinical visits, family members often ask me, is it necessary to change the environment for the patients to facilitate their rehabilitation? Desire is good, but the result is just the opposite. Dementia patients have poor capability of learning new things, therefore, environment change only makes they in a loss, accelerating the decline in self-care ability while exacerbating the disease progression. Therefore, for dementia patients, what we need to do is not to allow them to adapt to the environment, but create environment that is adapted to them. Try to keep everything in their living environment unchanged, however, in case compulsory to change, just change it gradually. Undoubtedly, in real life, change is always inevitable, so caregivers should try to make this change smaller and slower, instructing and training the patients repeatedly for the purpose of better adaption to the new change.

Management and counseling of BPSD symptoms for Dementia patients

1. Roaming:

There are several reasons for roaming behaviors in Dementia patients, such as dysgnosia, unfamiliar environment, fatigue, stress and anxiety, disturbance of consciousness, etc. For roaming at night, it is primarily associated with the loss of spatial orientation in the dark. Therefore, a better and safer living environment should be provided to the patients, for example, barrier-free space, room with obvious markers (using their most familiar items as markers), etc. Planning some activities for the patients can also effectively reduce roaming, improve their ability in social activities and increase their sense of pleasure and self-expression. These activities should be combined with their interests and previous life experiences, in order to increase their initiative in participation. Furthermore, in certain situations such as disturbance of consciousness, physical constraint is often the only way to stop roaming.

2. Self-care disability:

On one hand, nurses should provide repeated guidance and training to the patients, to enable them for acquiring basic living skills; on the other hand, they should care all aspects of well-being thoughtful for the patients. In many cases, taking care of dementia patients, is just like taking care of a two or three year-old child, who is not able to be alone for a moment.

3. Incontinence or poor care:

Most dementia patients have incontinence problems, which often increase the risk of infections and skin diseases, and seriously affect their life quality. Thus, obvious toilet signs should be provided near their living area; in addition, they should regularly be reminded to go to the toilet, for the purpose of retraining their habits of urination or defecation.

4. Eating disorders:

Anorexia, bulimia, and eating by hands are quite common in dementia patients, so taking good care of their eating habit has a direct impact on their health. Therefore, meals should regularly be provided, with nutritious and digestible food; meanwhile, recipes based their food preferences should also be arranged well, to avoid anorexia. Feeding should be slow down, so the patients can take enough time to have the food well chewed.

5. Sexual abnormalities:

Abnormalities in sexual behaviors are quite common among elderly dementia patients, and the gender differences are not evident, including being naked and masturbation in front of the opposite sex, etc. Caregivers should not be too nervous for that, and if time and occasion are inappropriate, try to persuade the patients gently, with more patience; never to rebuke and scold them, because this may be the last happiness in their lives. Rather than stopping, it is better to provide a more suitable environment or site for them to release.

6. Psychiatric symptoms:

When patients have hallucinations and delusions, do not argue with them; instead, you should distract their attention, and explain it to them in patience; meanwhile, you should seek a psychiatrist for advice and treatment promptly. For their violent and aggressive behaviors, try to counsel, explain, distract them, and use psychotropic substances for short-term control, under the guidance of clinicians; at the same time, the causes of their unpleasant experience should be analyzed and identified to prevent them from happening again.

7. Insomnia:

Disorders of sleep rhythm occur quite often in Dementia patients. They rest during the day while make noises at night, without any patterns at all, which makes the caregivers exhausted. Usually, relying on sleeping pills blindly cannot solve this problem, but aggravating the sleep disorders by disturbing the sleep rhythm, or even cause adverse events such as excessive sedation and falling down, which may increase the burden on caregivers. Daily training is a better way to solve this issue, which means the patients are not allowed to sleep in the daytime; on the contrary, try to maintain excitement by allowing them for participating more activities, so that they can rest at night, with healthy sleep rhythm. In addition, in a special case of roaming aimless at night, it is not because of the patient’s insomnia; instead, the patient simply forgot where the bed is. At this time, as long as the caregivers bring the patients back to the beds, this problem will be solved.

Treatment step 2: application of nootropic drugs.

On one hand, evidence showed that, nootropic drugs such as cholinesterase inhibitors and NMDA receptor antagonists can slow down the cognitive decline, and thereby have a direct therapeutic effect on some symptoms of BPSD. On the other hand, slowing down the cognitive decline can partially reduce the incidence of BPSD.

Treatment step 3: application of sedative hypnotics

Although the overall adverse reactions are less than the other psychoactive drugs such as antipsychotics, sedative hypnotics may have an adverse impact on daily operations and cognitive function in elderly patients; therefore, it should be careful when using them. It is recommended to use these sedative hypnotics prior to antipsychotics. Lorazepam and zopicl may be used as preferred choices, with a starting dose no exceed than 1/4-1/3 of their regular doses.

Treatment step 4: application of antipsychotics

If BPSD symptoms are still severe, with no satisfactory results after the above three treatment steps, we have to choose antipsychotics; however, it is noted that the step 4 is the last resort option. Studies have shown that antipsychotics may not only exaggerate cognitive impairment, but also increase the risk of fatal cardiac events. In addition, these drugs are likely to cause extrapyramidal reactions, or may have an impact in glucose and lipid metabolism, which means the injuries caused by the adverse reactions are likely to offset the gains of their therapeutic benefits. When we have no choice but antipsychotics, it is recommended to refer to the suggestions for the use of antipsychotics, in the "Guideline for Prevention of Dementia" formulated by Chinese Medical Association in 2007.

1. Aim at the "target symptoms";

2. Start with the minimum effective dose;

3. Adjust dose according to disease condition;

4. Use lower starting dose, and adjust the dose in lower range with longer interval;

5. Be alert of drug-related adverse reactions and drug interaction.

In addition, drug combination and long-lasting formulations should be avoided.

Commonly used psychotropic drugs in Dementia patients

Antipsychotics: including haloperidol, quetiapine, olanzapine, risperidone, etc. These drugs have positive therapeutic effects for treating exciting, hallucinations, thought disorder, and impulsive behavior in dementia patients; however, they also have adverse reactions such as excessive sedation, extrapyramidal reactions, abnormal lipid metabolism, cognitive deterioration, etc. Extrapyramidal reactions are more obvious among patients with traditional antipsychotics, whereas for atypical antipsychotics, the effects on glucose and lipid metabolism are relatively severe; meanwhile, both two types of drugs have similar risk of cardiovascular disease. Quetiapine and olanzapine have stronger sedation effect, which are more suitable for patients with refractory excitement. As they cause less extrapyramidal reactions, they are more suitable for treating patients with Parkinson's dementia.

Antidepressants: Antidepressants are often prescribed during the treatment of emotional disturbance, stress, anxiety, and dysthymia in dementia patients. The commonly used antidepressants are selective serotonin reuptake inhibitor (SSRIs) and serotonin–norepinephrine reuptake inhibitor (SNRIs), for example, mirtazapine, sertraline, citalopram, fluvoxamine, etc. Their adverse reactions are mild, thereby can be well tolerated by patients; some studies show that they can improve cognitive decline. However, it should be noted that during the early stage patients might have mild gastrointestinal discomfort while some patients could experience stress and anxiety. Among these drugs, sertraline and citalopram have fewer drug interactions, therefore, they can be used for the combination therapy of elderly patients; mirtazapine has better sedation and anxiolytic effects, can be used for patients with severe anxiety. It should be cautious for the anticholinergic effects of paroxetine, the drug interaction of fluoxetine due to its long half-life, and blood pressure monitor for venlafaxine. Traditional tricyclic antidepressants should be used with caution in the elderly patients, because they have strong anticholinergic effects, which may have an evident impact on the cardiovascular system.

Anxiolytic drugs: benzodiazepines, buspirone, tandospirone, etc., are commonly used. Among these anxiolytic drugs, benzodiazepine is most frequently used, due to its precise and fast anxiolytic effect. However, its adverse reactions such as muscle relaxation, cognitive impairment are very clear that it should be used appropriately for the treatment; moreover, its dose and treatment duration should be controlled strictly as well. For buspirone and tandospirone, it takes a few weeks to exert the anxiolytic effect, thereby are less used in the clinic for the treatment of dementia patients.

Emotional stabilizers: including sodium valproate, lithium etc., can be helpful in the control of aggressive behavior and exciting agitation in patients with dementia. Gastrointestinal reactions and liver function should be monitored when using sodium valproate; for lithium, it can lead to drug poisoning, hence the blood concentration should be the monitored when using lithium.

Treatment of several common BPSD symptoms in elderly patients with dementia

Delusions of being stolen: the nature of delusions of being stolen is forgetting and loss of self-knowledge, instead of real “delusion”; therefore, as antipsychotics treatment is not effective, psychological counseling and nootropic therapy would be the primary selections.

Illusion: it is very common that Dementia patients have auditory and visual hallucinations. For auditory hallucinations, risperidone or haloperidol can be used for treatment since they have less sedative effect; for visual hallucinations, the possibility of delirium and Lewy body dementia should be first considered, and relevant measures should be taken rather than antipsychotics.

Anxiety and mood disorders: anxiety in patients with dementia is atypical, usually present as abnormal behaviors such as restless, frequently going to the toilet, which need to be carefully judged. Drugs such as lorazepam and mirtazapine can be selected for treatment.

Agitation and impulsive behavior: when persistent agitation and impulsive behaviors exist in patients with dementia, it is inevitable to use antipsychotics. When the symptom is mild, lorazepam and valproate can be used. Antipsychotics with strong sedative effect such as quetiapine and olanzapine can be considered for severe patients.

Insomnia: for patients with disorders in sleep rhythm, as if day and night are reversed, rhythm can be corrected by non-pharmacological methods. Hypnotics such as zopiclone and lorazepam, or antidepressant with strong sedative effect such as mirtazapine can be used for intractable insomnia. Antipsychotics with strong sedative effects, including quetiapine and olanzapine can be used for severe insomnia.

Delirium: during the course of Dementia patients, delirium is very common but not easy to identify; sometimes it will seriously harm patient’s health and the overall life quality of their family. The reasons of delirium are very complicated, and it hard to make a clear conclusion for that; but generally, it can be considered from the following aspects:

1. Predisposition factor: for the brain with degenerative diseases, the synthesis of the central acetylcholine is largely reduced, thereby the sleep-wake cycle is perturbed, and ability to regulate the internal environment for maintaining the stability is reduced; the body becomes high vulnerable to any cause of hypoxemia. Besides, drug metabolism decreased and hence patient can be highly susceptible to drug-induced delirium.

2. Physical factors: include cardiovascular diseases, various infections, withdrawal symptoms, nutritional diseases, fluid and electrolyte imbalances, endocrine diseases, surgery or traumatic injuries, metabolic diseases, cerebrovascular diseases, alcohol or drug poisoning (by diuretics, sedative-hypnotics, painkillers, antihistamines, antiparkinsonian drugs, antidepressants, antipsychotics, and digitalis drugs).

3. Psychological factors: based on aging or physical factors induced brain damage, elderly patients are highly vulnerable to a wide range of psychosocial stressors, especially after major life events such as widowed, moving to an unfamiliar environment, family breakdown, etc., therefore, they becomes more easily to have delirium.

4. Other factors: substance dependence, dehydration, pain, sleep or sensory deprivation can also cause delirium in elderly patients.

Clinical manifestations of delirium include:

·           Loss of consciousness: the clarity of consciousness in patients declines, with disorientation and incoherency in thinking and speaking; besides, they might have a lot of illusion and hallucinations, especially the visual hallucinations that cannot be recalled afterwards.

·           Attention disorder: patients have distractibility, poor active and passive attention, dazed look, inability of maintaining purposeful, meaningful remove or staying focused.

·           Sleep-wake cycle disorders: in daytime, patients may become sleepy while at night they become excited.

·           Cognitive impairment: patients may have confusion in orienting time, place, and character, and may have a lot of illusion and hallucinations, particularly with visual hallucinations, incoherence in thought, and memory impairment; they can not remember what happened afterwards.

·           Emotional and behavioral disorders: patients with delirium show impaired reality testing capacity, believing that the illusions and hallucinations appeared are true, thereby they generate corresponding emotional and behavioral reactions. Nervous and fear, excitement, restlessness, random groping with unknown purposes are commonly observed among these patients.

Identification of delirium and dementia

Treatment of delirium

Delirium is a medical emergency and usually prompts a poorer prognosis and higher mortality, requiring emergent treatment by clinicians. The goal of treatment is not only to control exciting agitation, but more importantly, is to find, identify, and eliminate the precipitating factors that lead to the occurrence of delirium; only have this done, delirium can truly be corrected and mortality can be decreased.  

For the treatment of acute delirium, on one hand, vital signs and the state of consciousness in patients need to be monitored, to maintain the patency and adequate oxygen supply in the airway, and to improve blood circulation so as to provide the vital organs such as brain, heart with oxygen. At the same time, we should also terminate all unnecessary drugs, and intervene the identified precipitating factors. Afterwards, it is necessary to control the excitement and to eliminate illusion and hallucinations. According to the American Psychiatric Association Guidelines that published in 1999, haloperidol was still the first-line drug for the treatment of delirium. Moreover, in recent years, it has been reported that atypical antipsychotics and cholinesterase inhibitors have a positive effect in the treatment of delirium, although the evidence are not sufficient. On the other hand, we should pay more attention to the management of delirium patients, to provide them a bright, quiet, and clean environment for rest, and to arrange specially-assigned person that are familiar with the patients for health care. In addition, proper diet should be provided, ensuring their intake and output, to prevent them from accidental injuries.

Bao Feng

Section 7 Recommendations for AD Patient Longitudinal Support Program