Latimer Caitlin S, Keene C Dirk, Flanagan Margaret E, Hemmy Laura S, Lim Kelvin O, White Lon R, Montine Kathleen S, Montine Thomas J
From the Department of Pathology, University of Washington, Seattle, Washington (CSL, CDK); Department of Pathology, Stanford University, Stanford, California (MEF, KSM, TJM); Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota (LSH, KOL); Geriatric Research, Education, and Clinical Center, Minneapolis VA Health Care System, Minneapolis, Minnesota (LSH); Pacific Health Research and Education Institute (PHREI), Honolulu, Hawaii (LRW); and Department of Geriatric Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii (LRW).
J Neuropathol Exp Neurol. 2017 Jun 1;76(6):458-466. doi: 10.1093/jnen/nlx030.
Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases.
两项基于人群的研究对于推进脑老化知识至关重要，即檀香山-亚洲老年研究（HAAS）和修女研究。对它们的神经病理学数据进行整合可实现交叉比较，两项研究共有的发现可能具有普遍意义，而不同的观察结果可能指向依赖于性别、种族、环境或生活方式因素的脑老化变化。在此，我们使用修订后的美国国立衰老研究所-阿尔茨海默病协会指南扩展了这两项研究的神经病理学评估，并直接比较了抗损伤能力和明显认知恢复力的神经病理学特征。这两项研究在阿尔茨海默病神经病理学改变、小血管性脑损伤和路易体病的患病率方面存在显著差异，表明性别、种族和生活方式因素可能会显著影响随着年龄增长对脑损伤发展的抵抗力。相比之下，海马硬化的患病率非常相似，但偏向于较差的认知表现，这表明海马硬化可能与其他疾病相继作用以损害认知功能。引人注目的是，尽管观察到了这些差异，但HAAS和修女研究参与者中对所有4种脑部疾病具有抵抗力或表现出明显认知恢复力的个体比例几乎相同。这些结果未来的体内验证有待这4种脑部疾病的综合生物标志物。
