Alzheimer’s and aging neuropathologies diverge in cognitively healthy centenarians

Cognitive impairment is not inevitable at extreme ages, according to a 1.6-year longitudinal study of 340 individuals who were 100 years old and above, which examined the cohort’s cognitive resilience and resistance to cognitive impairment. Comprehensive cognitive function testing was performed annually, and the study also examined how individual subjects belied expectations of senescence and symptoms of the onset of Alzheimer’s disease. “During  1.6  years of follow-up, no decline in cognitive function was observed except for a minor decrement in memory,” of a type that may be revealed in cognitive testing.

Other insights from centenarian populations are discussed in commentary by Thomas T. Perls, MD, MPH in his JAMA article, “Cognitive Trajectories and Resilience in Centenarians—Findings From the 100-Plus Study,” which references the work of Nina Beker, PhD; Andrea Ganz, MSc; Marc Hulsman, PhD et al under the auspices of the University of Amsterdam, in “Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline.”

As an aging-related condition, Alzheimer’s disease (AD) has long been considered an expected consequence of extreme old age, but neurologist Dr. John Morris contended otherwise, pointing out common mistakes that have led to the supposition of inevitability. Within the Beker study, long-term in-depth testing correlated with data from autopsies of 10% of the subjects (indicating some divergence between neuropathologies of Alzheimer’s disease and aging) revealing that these individuals were both cognitively intact despite aged brain structures (associated with Alzheimer’s-related pathologies), aged 90 and up. 

Rather than subscribing to the assumptive perspective that a person is “doing well” despite extreme age, the study’s results suggest we should rely on sensitive and specific diagnostic criteria no matter what the age. Further, longitudinal study is superior to cross-sectional study for achieving reliable levels of sensitivity and specificity regarding biological, behavioral, and other factors.  

Individuals over 100 are rare, and those with full cognitive function are rarer still. These anomalous folks, as an expressive, communicative group, proved helpful in uncovering unique elements of behavior, environment, and/or biology, all potential mechanisms of resistance and resilience to AD and related dementias. The epidemiological road to more effective treatment, or even a cure, may emanate from finding the source of these centenarians’ resilience/resistance! 

Various studies support the proposal that centenarians have undefined and beneficial protective mechanisms. Studies have demonstrated that there is an increasingly strong genetic influence with age beyond approximately 95 years. It’s more than hopeful that the Beker Study has the potential of discovering how and why these rare individuals delay or escape Alzheimer’s disease and other dementias.



“Understanding mechanisms associated with prolonged cognitive health in combination with exceptional longevity might lead to approaches to enable successful aging.

These findings indicate that prolonged maintenance of cognitive functioning may be supported by mechanisms underlying resilience against risk factors of cognitive decline,” writes Perls. 

Toward this end, it’s incumbent upon medical professionals and caregivers to be vigilant in tracking and testing all at risk of cognitive decline. The advances modern medicine will acquire through studies of folks like these centenarians allows for hope for potential intervention and thwarting the progression of cognitive impairment. 

Regular cognitive assessment regimens should be considered essential for elderly patients to protect their current cognitive function and to detect and intervene at the earliest signs. If at some future date treatments are introduced, all behavioral, environmental, or biological markers of individual patients will be scrutinized for relevance to these treatments. For current and future effectiveness, proper testing can enable treatment protocols to be applied in a timely fashion. BrainCheck provides an easy to use, fully reimbursable cognitive assessment tool which can fit into any provider’s treatment and assessment plan.

Find out more about how BrainCheck can benefit your practice. Contact us today using this link.

Related Topics

Get BrainCheck’s future articles in your box

Get the latest clinical news and research delivered to your email inbox, and receive our latest articles on topics relevant to your practice.

Provide Cognitive Care, Anywhere with BrainCheck.

Braincheck results and reports dashboard
Scroll to Top

Schedule your demo!

Get Our FREE Product Guide

Complete the Form to Download