Centenarians as Models of Resistance and Resilience to Alzheimer's Disease and Related Dementias.

The majority of research to understand the pathogenesis of and contributors to Alzheimer's disease (AD) pathology, dementia, and disease progression has focused on studying individuals who have the disease or are at increased risk of having the disease. Yet there may be much to learn from individuals who have a paradoxical decreased risk of AD suggesting underlying protective factors. Centenarians demonstrate exceptional longevity that for a subset of the cohort is associated with an increased health span characterized by the delay or escape of age-related diseases including dementia. Here, I give evidence of the association of exceptional longevity with resistance and resilience to AD and describe how cohorts of centenarians and their offspring may serve as models of neuroprotection from AD. Discoveries of novel genetic, environmental, and behavioral factors that are associated with a decreased risk of AD may inform the development of interventions to slow or prevent AD in the general population. Centenarian cohorts may also be instrumental in serving as controls to individuals with AD to identify additional risk factors.