Resilience and resistance to the accumulation of amyloid plaques and neurofibrillary tangles in centenarians: An age-continuous perspective

IntroductionWith 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? MethodsIn 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. ResultsWith 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). DiscussionCognitive health can be maintained despite the accumulation of high levels of AD-related neuropathological substrates. HighlightsCognitively 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.

Automated summary

In this study, the brains of centenarians were examined to determine whether they exhibited resistance or resilience to Alzheimer's disease-related neuropathological substrates. The results showed that some centenarians maintained cognitive health despite the presence of high levels of AD-related neuropathology.