Resilience and resistance to Alzheimer’s disease-associated neuropathological substrates in centenarians: an age-continuous perspective

INTRODUCTION With increasing age, neuropathology associated with Alzheimer’s disease (AD) accumulates in brains of cognitively healthy individuals: are they resilient or resistant against AD-associated neuropathologies? METHODS In 85 centenarian brains, we correlated NIA-Amyloid stages, Braak-NFT stages and CERAD-NP scores with cognitive performance determined close to death (MMSE). We assessed centenarian brains in context of 2,131 brains from AD patients, non-AD demented and non-demented individuals (age-range 16-100+ years). RESULTS With age, brains from non-demented individuals reached NIA-Amyloid and Braak-NFT stages as observed in AD patients, while CERAD-NP scores remained lower. In centenarians, NIA-Amyloid stages varied (22.4% had the highest stage 3), Braak-NFT stages rarely exceeded IV (5.9% had stage V), and CERAD-NP scores rarely exceeded 2 (4.7% had score 3); within these distributions, we observed no correlation with MMSE (NIA-Amyloid: P =0.60; Braak-NFT: P =0.08; CERAD-NP: P =0.16). DISCUSSION Cognitive health can be maintained despite the accumulation of high levels of AD-related neuropathological substrates. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Dioraphte (VSM 14 04 14 02) and Stichting VUmc Fonds. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Medical Ethics Committee of the VU University Medical Center gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.