Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Delft Bioinformatics Lab, Delft Technical University, Delft, The Netherlands.
Alzheimers Dement. 2023 Jul;19(7):2831-2841. doi: 10.1002/alz.12899. Epub 2022 Dec 30.
With increasing age, neuropathological substrates associated with Alzheimer's disease (AD) accumulate in brains of cognitively healthy individuals-are they resilient, or resistant to AD-associated neuropathologies?
In 85 centenarian brains, we correlated NIA (amyloid) stages, Braak (neurofibrillary tangle) stages, and CERAD (neuritic plaque) scores with cognitive performance close to death as determined by Mini-Mental State Examination (MMSE) scores. We assessed centenarian brains against 2131 brains from AD patients, non-AD demented, and non-demented individuals in an age continuum ranging from 16 to 100+ years.
With age, brains from non-demented individuals reached the NIA and Braak stages observed in AD patients, while CERAD scores remained lower. In centenarians, NIA stages varied (22.4% were the highest stage 3), Braak stages rarely exceeded stage IV (5.9% were V), and CERAD scores rarely exceeded 2 (4.7% were 3); within these distributions, we observed no correlation with the MMSE (NIA: P = 0.60; Braak: P = 0.08; CERAD: P = 0.16).
Cognitive health can be maintained despite the accumulation of high levels of AD-related neuropathological substrates.
Cognitively healthy elderly have AD neuropathology levels similar to AD patients. AD neuropathology loads do not correlate with cognitive performance in centenarians. Some centenarians are resilient to the highest levels of AD neuropathology.
随着年龄的增长，与阿尔茨海默病（AD）相关的神经病理学基础在认知健康个体的大脑中积累——他们是有弹性的，还是对 AD 相关神经病理学有抵抗力？
在 85 名百岁老人的大脑中，我们将 NIA（淀粉样蛋白）阶段、Braak（神经原纤维缠结）阶段和 CERAD（神经原纤维缠结）评分与接近死亡时的认知表现（由 Mini-Mental State Examination [MMSE] 评分确定）相关联。我们评估了百岁老人的大脑与 2131 名 AD 患者、非 AD 痴呆和非痴呆个体的大脑进行了对比，这些个体的年龄范围从 16 岁到 100 岁以上。
随着年龄的增长，非痴呆个体的大脑达到了 AD 患者观察到的 NIA 和 Braak 阶段，而 CERAD 评分仍然较低。在百岁老人中，NIA 阶段存在差异（22.4%为最高的第 3 阶段），Braak 阶段很少超过第 IV 阶段（5.9%为第 V 阶段），CERAD 评分很少超过 2（4.7%为第 3 阶段）；在这些分布中，我们没有观察到与 MMSE 的相关性（NIA：P=0.60；Braak：P=0.08；CERAD：P=0.16）。
尽管积累了高水平的 AD 相关神经病理学基础，但认知健康仍能得到维持。
认知健康的老年人具有与 AD 患者相似的 AD 神经病理学水平。AD 神经病理学负荷与百岁老人的认知表现无关。一些百岁老人对 AD 神经病理学的最高水平有抵抗力。
