Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Neuroscience& Experimental Psychology, University of Manchester, Salford Royal Hospital, Salford, UK.
J Alzheimers Dis. 2018;64(2):483-496. doi: 10.3233/JAD-180171.
The neuropathological changes responsible for cognitive impairment and dementia remain incompletely understood. Longitudinal studies with a brain donation end point allow the opportunity to examine relationships between cognitive status and neuropathology. We report on the first 97 participants coming to autopsy with sufficient clinical information from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age. This study began in 1983 and recruited 6,542 healthy individuals between 1983 and 1994, 312 of whom consented to brain donation. Alzheimer-type pathology was common throughout the cohort and generally correlated well with cognitive status. However, there was some overlap between cognitive status and measures of Alzheimer pathology with 26% of cognitively intact participants reaching either CERAD B or C, 11% reaching Thal phase 4 or 5, and 29% reaching Braak stage III- VI. Cerebral amyloid angiopathy(CAA), α-synuclein, and TDP-43 pathology was less common, but when present correlated well with cognitive status. Possession of APOEɛ4 allele(s) was associated with more severe Alzheimer-type and CAA pathology and earlier death, whereas possession of APOEɛ2 allele(s) had no effect on pathology but was more common in cognitively intact individuals. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort is pathologically representative when compared with similar studies. Cognitive impairment in life correlates strongly with all pathologies examined and the APOE status of an individual can affect pathology severity and longevity.
导致认知障碍和痴呆的神经病理学变化仍不完全清楚。具有脑捐献终点的纵向研究使我们有机会检查认知状态与神经病理学之间的关系。我们报告了来自曼彻斯特大学正常健康老年认知纵向研究的前 97 名参与者，这些参与者具有足够的临床信息进行尸检。该研究始于 1983 年，在 1983 年至 1994 年间招募了 6542 名健康个体，其中 312 人同意捐献大脑。阿尔茨海默病型病理学在整个队列中很常见，通常与认知状态密切相关。然而，认知状态与阿尔茨海默病病理学测量之间存在一些重叠，26%认知正常的参与者达到 CERAD B 或 C，11%达到 Thal 阶段 4 或 5，29%达到 Braak 阶段 III-VI。脑淀粉样血管病（CAA）、α-突触核蛋白和 TDP-43 病理学较少见，但存在时与认知状态密切相关。APOEɛ4 等位基因（s）的存在与更严重的阿尔茨海默病型和 CAA 病理学以及更早的死亡有关，而 APOEɛ2 等位基因（s）的存在对病理学没有影响，但在认知正常的个体中更为常见。与类似的研究相比，曼彻斯特大学正常健康老年认知纵向研究队列在病理学上具有代表性。生活中的认知障碍与所有检查的病理学密切相关，个体的 APOE 状态可以影响病理学严重程度和寿命。
