Cognitive resilience and severe Alzheimer’s disease neuropathology

Cognitive resilience in Alzheimer’s disease (AD) can be defined as retention of high cognition despite presence of considerable cerebral AD lesions. We sought to identify factors associated with this phenomenon. Data were obtained from National Alzheimer’s Coordinating Centre (NACC) dataset. Subjects with severe AD neuropathology, based on National Institute on Aging–Reagan (NIA-Reagan) criteria, no other primary neuropathology, and a ≤ 2-year interval between last follow-up and death were included. Mini-mental status examination score ≥ 24 was used as a proxy for normal cognition. In total, 654 cases were included; 59 (9%) were cognitively resilient. Multivariable logistic regression model showed that resilient participants were more educated, had a lower body mass index (BMI), were more likely to be lifetime/recent smoker or use an anticoagulant/antiplatelet agent, compared with cognitively impaired subjects. In addition to expected protective factors such as higher education and lower BMI, our results showed that smoking (especially recent smoking) and anticoagulant/antiplatelet consumption are associated with resilience to clinical cognitive expression of severe AD pathology. Pharmacological approaches using this information might be explored for clinical AD amelioration.