Department of Biostatistics & Medical Informatics, School of Medicine & Public Health, University of Wisconsin, Madison, WI 53792, USA.
J Int Neuropsychol Soc. 2011 Jul;17(4):602-14. doi: 10.1017/S1355617710001426.
Studies of neuropathology-cognition associations are not common and have been limited by small sample sizes, long intervals between autopsy and cognitive testing, and lack of breadth of neuropathology and cognition variables. This study examined domain-specific effects of common neuropathologies on cognition using data (N = 652) from two large cohort studies of older adults. We first identified dimensions of a battery of 17 neuropsychological tests, and regional measures of Alzheimer's disease (AD) neuropathology. We then evaluated how cognitive factors were related to dimensions of AD and additional measures of cerebrovascular and Lewy Body disease, and also examined independent effects of brain weight. All cognitive domains had multiple neuropathology determinants that differed by domain. Neocortical neurofibrillary tangles were the strongest predictors of most domains, while medial temporal tangles showed a weaker relationship with episodic memory. Neuritic plaques had relatively strong effects on multiple domains. Lewy bodies and macroscopic infarcts were associated with all domains, while microscopic infarcts had more limited associations. Brain weight was related to all domains independent of specific neuropathologies. Results show that cognition is complexly determined by multiple disease substrates. Neuropathological variables and brain weight contributed approximately a third to half of the explained variance in different cognitive domains.
神经病理学-认知关联的研究并不常见，并且受到样本量小、尸检和认知测试之间间隔时间长以及神经病理学和认知变量范围有限的限制。本研究使用来自两项关于老年人的大型队列研究的数据（N=652），考察了常见神经病理学对认知的特定领域的影响。我们首先确定了一组 17 项神经心理学测试和阿尔茨海默病（AD）神经病理学的区域测量的维度。然后，我们评估了认知因素与 AD 以及其他脑血管和路易体疾病测量值的维度之间的关系，还检查了脑重量的独立影响。所有认知领域都有多个神经病理学决定因素，这些决定因素因领域而异。皮质神经原纤维缠结是大多数领域的最强预测因子，而内侧颞叶缠结与情景记忆的相关性较弱。神经原纤维缠结对多个领域都有较强的影响。路易体和大的脑梗死与所有领域都有关，而小的脑梗死的相关性则有限。脑重量与所有领域相关，与特定的神经病理学无关。结果表明，认知是由多种疾病底物复杂决定的。神经病理学变量和脑重量对不同认知领域的解释方差的贡献约为三分之一到一半。
