运动有助改善老年人认知功能

温哥华——阿尔茨海默病学会2012年国际会议7月15日公布的多项研究共同表明，体力活动对于保护认知健康至关重要。这些研究显示，体力活动不仅可改善心肺功能，而且还能增加脑容量，改善认知功能，以及加快神经元生长。

温哥华英属哥伦比亚大学衰老、活动和认知神经科学实验室的Teresa Liu-Ambrose博士及其同事开展一项随机对照研究，探讨了3种不同训练方案的益处：抗阻训练、有氧训练、平衡与张力训练(对照组)。各种训练每周进行1次，持续6个月。受试者为86名70~80岁的女性。所有受试者均在家居住，但可能存在轻度认知功能损害。各组的训练强度均不断增加。抗阻训练组从受试者所能承受的最大重量开始训练，一旦受试者能够超过所要求的重复次数，就继续增加重量。有氧训练组根据受试者的心率和主观运动强度来增加受试者的步行速度。对照组也随着研究的进行而增加重复次数和拉伸。6个月后，抗阻训练组的执行功能相对基线改善17%，显著优于其他组。此外，这些女性的联想记忆也获得显著改善。Liu-Ambrose博士还发现，认知结果与生理指标相关。功能MRI显示右舌回、枕叶梭状回和右额极这3个参与非言语联想的编码和记忆的脑区血流量增加。有氧训练组的平衡、活动性和心血管功能改善，但认知功能和脑生理功能未获得同样改善。平衡和张力组的认知功能得以维持，未出现进一步下降，但也未获得进一步改善。Liu-Ambrose博士表示，抗阻训练组受试者获得了真正的改善，这表明训练不仅可预防轻度认知功能损害进一步恶化，而且还具有潜在的治疗作用。

在另一项研究中，匹兹堡大学的认知神经科学研究人员Kirk Erickson博士发现了训练诱导的脑容量改变的分子基础。Erickson博士表示，体力活动可刺激释放促进神经元生长的分子。这项研究纳入120名入组前处于久坐生活方式至少6个月的认知功能正常的老年人。受试者被随机分成两组，一组接受为期1年的中等强度步行训练，另一组接受为期1年的拉伸和张力训练组。基线时和1年时，测定脑容量和脑源性神经营养因子(BDNF)水平。研究结束时，步行训练组的前海马容量较拉伸和张力训练组增加2%。BDNF的增加与容量改变呈正相关。此外，还发现额前皮质容量的增加与心肺功能增加相关。

Liu-Ambrose博士表示，尚不完全清楚如何在日常生活中有效实施这些实验性的训练方案，因为对于认知功能损害的患者而言，他们在计划和安排事情方面本已存在困难。英属哥伦比亚大学的Nader Fallah博士根据其在生物统计学方面的经验，对这一问题进行了探讨。他对一项为期12个月的随机对照研究中的155名65~75岁女性进行了二次分析(Neurobiol. Aging 2012;33:1690-8)。在这项研究中，受试者被分入抗阻训练组或平衡和张力训练组。分析表明，基线认知功能较高的女性从抗阻训练中获得的益处最大。基线功能较低的女性不仅从训练中获得的改善较少，而且对抗阻训练及平衡和张力训练的反应也相同。Fallah博士表示，这项研究首次发现，患者的基线自我调节能力可影响其从目标训练中获得的认知功能方面的益处。这项研究结果表明，“认知启动”(cognitive priming)可改善接受训练的患者的预后。Liu-Ambrose博士表示，这给医生们提供了另一个思考的角度：当医生对患者采取某种训练方案时，更多注重的是机体的能力，即患者膝关节能否承受这种训练、患者心血管状态如何等。但基线时具有较好执行功能的患者能够更好地执行医生为其处方的训练，而痴呆较明显的患者则只能更多依靠照顾者的帮助。

上述研究者均声明无经济利益冲突。

爱思唯尔  版权所有

By: MICHELE G. SULLIVAN, Family Practice News Digital Network

VANCOUVER – Physical activity improves not only the heart and lungs, but the brain as well, providing a triad of benefits: improved cognition, better physiologic functioning, and increased brain volume and hints of revved-up neuronal growth.

Studies presented July 15 at the Alzheimer’s Association International Conference 2012 agreed: Getting active is essential for preserving cognitive health.

Exactly how exercise boosts brain function is still a matter of debate, Teresa Liu-Ambrose, Ph.D., said in an interview.

"In addition to getting the physical benefits of exercise, people are also getting social interaction and mental stimulation," said Dr. Liu-Ambrose, director of the Aging, Mobility, and Cognitive Neuroscience Lab at the University of British Columbia, Vancouver. Group activities, like exercise, can also help unwind the tangle of diminished executive function and social isolation, a damaging pair.

"When executive function begins to deteriorate, people know that they are losing some of their ability to interact, and so they withdraw and become isolated," she said. The lack of social interaction contributes to the downward slide of cognition.

Dr. Liu-Ambrose was the primary investigator of a randomized controlled trial that examined the benefits of three different exercise regimens, each conducted twice a week for 6 months: resistance training; aerobic training; and balance and tone training, which served as the comparator group.

The subjects were 86 women aged 70-80 years. They all still lived at home, but had probable mild cognitive impairment. The group is an important one because the natural history of Alzheimer’s disease suggests that about half of those who develop mild cognitive impairment will go on to develop Alzheimer’s dementia.

All of the programs were progressive, she said. Those in the weight program started with the largest weights they could handle with good form, which were increased as soon as the women exceeded the required number of repetitions. The aerobic group increased their walking speed based on heart rate and perceived exertion. The control group loaded their exercises as well, increasing repetitions and stretching as the trial progressed.

After 6 months, the strength training group had improved by 17% over baseline on measures of executive function, which was significantly better than either of the other groups. These women also experienced significant gains in associative memory.

Dr. Liu-Ambrose also saw physiologic correlates to the cognitive findings. Functional MRI showed improved blood flow in three brain regions involved with encoding and memorization of nonverbal associations: the right lingual gyrus, the occipital fusiform gyrus, and the right frontal pole.

The aerobic training group improved in balance, mobility, and cardiovascular capacity, but did not have the same kind of cognitive or brain physiologic gains, she added. The balance and tone group maintained their cognitive ability without any additional decline, but didn’t experience any additional benefit either.

"I want to stress that we were seeing a real improvement with resistance training – not just maintenance like we did in the control group. We’re talking about women who already have some level of cognitive impairment. The most positive way of looking at this is that exercise could be a magic bullet. There is evidence now that exercise may not only be preventive – but a potential treatment."

In a separate study, Kirk Erickson, Ph.D., presented evidence of the molecular underpinning of exercise-induced brain volume changes: Physical activity, he said, stimulates the release of molecules that promote neuronal growth.

Dr. Erickson, a cognitive neuroscience researcher at the University of Pittsburgh, described the results of a walking program that involved 120 cognitively healthy, elderly adults.

The participants had been sedentary for at least the previous 6 months. They were randomized either to a 1-year program of moderately intense walking or to a 1-year stretching and toning group. At baseline and at 1 year, Dr. Erickson and his colleagues measured brain volume and levels of brain-derived neurotrophic factor (BDNF).

BDNF is a protein that affects neurons in several ways: It supports healthy neuronal function, encourages stem cells to differentiate into neurons, and stimulates dendritic expansion. BDNF is particularly active in regions associated with memory and executive functioning.

At the study’s end, Dr. Erickson and his associates found that those in the walking program had about a 2% increase in the size of the anterior hippocampus, compared with the stretching and toning group. Increases in BDNF positively correlated with the volume change. He also saw increases in the volume of the prefrontal cortex, which correlated with increased cardiorespiratory fitness.

Just how to translate these controlled experimental situations into effective, real-life practice isn’t completely clear, Dr. Liu-Ambrose said, especially when patients already have difficulty with planning and prioritization.

Her colleague, Nader Fallah, Ph.D., also of the University of British Columbia, used his expertise in biostatistics to explore that problem. Using a similar cohort of women, he found that those with higher baseline cognitive function reaped the greatest benefit from resistance training.

Dr. Fallah conducted a secondary analysis of a 12-month, randomized, controlled trial of 155 women aged 65-75 years (Neurobiol. Aging 2012;33:1690-8). The women were assigned to resistance training or balance and tone training.

This new analysis found that women with lower baseline functioning not only experienced less improvement from exercise, but also responded equally to both resistance training and balance and tone training.

"To our knowledge, this is the first study to demonstrate that an individual’s baseline self-regulatory capacity impacts the amount of cognitive benefit the person will reap from targeted exercise training," Dr. Fallah said in a written statement.

Dr. Liu-Ambrose said the study sheds valuable light on the concept of personalizing exercise prescriptions.

"I think this brings us another dimension to consider," Dr. Liu-Ambrose said. "When we prescribe exercise, most of the time we focus on physical ability: ‘Can the knees take it, what is the cardiovascular state?’ But people who have better executive function at baseline can execute this prescription better. They can plan their time, prioritize their activities, and follow through with the commitment."

Dr. Fallah’s findings suggest that "cognitive priming" might improve outcomes in prescribed exercise. Computerized brain training games are one thing to consider. They’ve been shown to improve memory and executive function for both cognitively healthy and impaired older adults. Just a small improvement in executive function and memory could be enough to get a patient invested in an exercise program.

"But for those with more pronounced dementia, it’s really about engaging the caregiver," Dr. Liu-Ambrose concluded. "We need to give them the tools they need to implement this as part of the daily lives of their loved ones."

None of the researchers reported having any financial conflicts of interest.