血管病变比淀粉样蛋白更损害认知

《JAMA Neurology》2月11日在线版上发表的一项纳入61例老年受试者的研究显示，血管性脑损伤对认知功能的影响比β淀粉样蛋白沉积更大，至少在认知损害的最初阶段是这样(JAMA Neurol. 2013 Feb. 11 [doi:1001/2013.jamaneurol.405])。

加州大学伯克利分校Helen Wills 神经科学研究所的Natalie L. Marchant博士表示，上述发现提示，在评估轻度认知损害(MCI)时应考虑到脑梗死的影响，而且减少脑血管疾病可能对于预防MCI非常重要。

梗死区与β淀粉样蛋白沉积区在对老年患者进行脑部影像学检查时均比较常见，而且时常同时出现。MRI显示56%的受试者至少有1处梗死。采用β淀粉样蛋白结合配体匹兹堡复合物B(PiB)的PET成像显示，48%的受试者存在早期β淀粉样蛋白沉积。共有41%的受试者同时存在梗死和PiB阳性，56%的受试者无梗死但PiB阳性。

根据简易精神状态检查、老年抑郁量表、临床痴呆评级，以及针对执行功能、语言记忆和非语言记忆的一系列神经精神检查，共有30名受试者为临床正常，24人为MCI(7例为记忆缺失性、13例为非记忆缺失性，4例为其他类型MCI)，7人患有痴呆症。

结合神经精神检查和影像学检查结果，对受试者的认知功能进行比较，研究者发现血管性脑损伤与语言记忆、执行功能方面的认知损害强烈相关，而与非语言记忆受损关系不大。

而与此相对的是，β淀粉样蛋白沉积与认知损害无关。Marchant博士等人认为，二者在该样本中未显示出相关性，可能是由于这种沉积是初始事件，其“下游”后果(诸如神经元死亡和突触减少)尚未在这些受试者中发生。“而血管性脑损伤可能反映了血管性致病过程的终末期病理学后果。”

多变量逻辑回归分析显示，皮层下灰质中的梗死是唯一显著的语言记忆预测因素，受试者语言记忆的变异有17%是由这一因素引起的。仅有年龄和教育程度是非语言记忆的显著预测因素，受试者非语言记忆的变异有48%可归因于这2项因素。仅有皮层灰质中的梗死和教育程度是执行功能的显著预测因素，可解释43%的执行功能差异。

β淀粉样蛋白沉积与血管性脑损伤之间也无关联。可能原因是这两种异常在衰老的大脑中均较普遍，常常同时存在，并且以不同方式影响认知功能，但二者之间没有任何因果关系。

这项研究获得了国立卫生研究院的资金支持。Marchant博士报告称无相关利益冲突，但他的一名合著者承认与多家企业存在关联。

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By: MARY ANN MOON, Internal Medicine News Digital Network

Vascular brain injury had a greater influence on cognitive function than did beta-amyloid deposition, at least in the earliest phases of cognitive impairment, in a study examining the relative contributions of the two abnormalities in 61 elderly  participants.

The findings indicate that brain infarctions should be considered in studies of mild cognitive impairment (MCI), and that reducing cerebrovascular disease may be important in preventing MCI, said Natalie L. Marchant, Ph.D., of the Helen Wills Neuroscience Institute at the University of California, Berkeley, and her associates. They reported their findings online Feb. 11 in JAMA Neurology.

Both areas of infarction and areas of beta-amyloid deposition are frequently found on imaging studies of the brain in elderly subjects, and oftentimes both are present in the same individual, the investigators said. MRI revealed at least one infarct in 56% of the participants. PET imaging with the beta-amyloid binding ligand Pittsburgh compound B (PiB) found early beta-amyloid deposition in 48%. Overall, 41% had both an infarct and tested positive for PiB while 56% had no infarct but tested positive for PiB.

The study subjects had a range of cognitive functioning based on assessments made with the Mini-Mental State Examination, the Geriatric Depression Scale, the Clinical Dementia Rating, and a battery of neuropsychological tests of executive function, verbal memory, and nonverbal memory. Overall, 30 subjects were clinically normal, 24 showed MCI (7 with amne stic, 13 with nonamnestic, and 4 with other MCI), and 7 had dementia. The subjects were participating in an ongoing multicenter study, the Aging Brain Project.

Comparisons of the subjects’ cognitive function based on neuropsychological testing with the imaging results showed that vascular brain injury strongly correlated with cognitive impairment for verbal memory and executive function, but not nonverbal memory, the investigators said (JAMA Neurol. 2013 Feb. 11 [doi:1001/2013.jamaneurol.405]).

In contrast, beta-amyloid deposition did not correlate with cognitive impairment. The lack of an association in this sample might be because such deposition is an initiating event, and the "downstream" consequences such as neuronal death and synaptic loss have not yet occurred in these subjects, Dr. Marchant and her associates said.

In contrast, they suggested that "vascular brain injury represents end-stage pathologic consequences of the vascular pathogenic process."

An infarct in the subcortical gray matter was the only significant predictor of verbal memory in a multivariate logistic regression equation that accounted for 17% of the patient sample’s variance in verbal memory. The equation included white matter hyperintensity volume, infarct location in the subcortical gray matter, PiB status, and age, sex, and other demographic variables.

Only age and educational level were significant predictors of nonverbal memory in a multivariate logistic regression equation that accounted for 48% of the patient sample’s variance in nonverbal memory.

In a multivariate logistic regression equation that explained 43% of the variance in executive function, an infarct location in the cortical gray matter and educational level were the only significant predictors.

Beta-amyloid deposition also did not correlate with vascular brain injury. It may be that both of these abnormalities are prevalent in the aging brain, often occur concomitantly, and affect cognitive function in different ways, but do not bear any causal relationship to each other, the investigators said.

This study was supported by grants from the National Institutes of Health. Dr. Marchant reported no financial conflicts of interest, but one of her associates reported ties to numerous industry sources.