By Grace Niewijk
Many people assume that some memory decline is an inevitable consequence of getting older. But a select group of older adults, known as SuperAgers, reach their 80s and 90s while retaining memory performance as good as or better than people in their 50s and 60s.
Nearly two decades of research has identified unique biological, brain, and psychosocial characteristics associated with SuperAgers, but an important question has remained: Could SuperAgers simply be people who inherited very little genetic risk for Alzheimer’s disease?
“If that were true, identifying SuperAgers might be as simple as performing genetic testing rather than the comprehensive cognitive evaluations we currently use,” said Emily Rogalski, PhD, director of the Healthy Aging & Alzheimer’s Research Care (HAARC) Center at the University of Chicago, who established the definition of SuperAging in 2008 and has been studying this remarkable population ever since.
A new study aimed to directly test that hypothesis using the largest prospectively enrolled SuperAging cohorts and the most up-to-date Alzheimer's genetic risk measures available. The findings, published in Alzheimer’s Research & Therapy, show that exceptional memory aging cannot be explained simply by low inherited Alzheimer's disease risk, reinforcing the importance of studying protective pathways directly.
A team led by researchers at the HAARC Center and the Translational Genomics Research Institute (TGen), part of City of Hope, studied a diverse cohort from across five regional sites in the U.S. and Canada, comprised of 142 SuperAgers and 89 cognitively average peers. Using DNA extracted from blood samples, the researchers examined the APOE gene, the strongest genetic risk factor for Alzheimer’s disease, and calculated three polygenic risk scores, which tally thousands of genetic variants associated with inherited Alzheimer’s disease risk.
The results provided a clear answer to the central question: SuperAgers could not be distinguished from cognitively average older adults based on either APOE or Alzheimer's polygenic risk scores. In other words, having exceptional memory in one’s 80s is not simply explained by having exceptionally low inherited Alzheimer's disease risk.
“The findings reinforce that preserving cognitive health involves more than reducing Alzheimer's disease risk alone,” said co-first author Ana Capuano, PhD, director of the biostatistics core at the HAARC Center. “Understanding the biological, behavioral, and social factors that promote exceptional cognitive aging may ultimately complement traditional disease-focused approaches and help inform more personalized strategies for supporting brain health across the lifespan.”