SuperAgers' Alzheimer's genes do not explain youthful memory, study finds

A new study of SuperAgers and Alzheimer's genes found that unusually strong memory in old age cannot be explained by a lower inherited risk for Alzheimer's disease. Researchers said the finding shifts attention toward other forces that may protect memory, including brain biology, health, behavior, social factors and environment.

The work, reported by the University of Chicago Medical Center, examined people known as SuperAgers: adults in their 80s and 90s whose memory performance matches or exceeds that of people decades younger. Scientists have studied this group for nearly 20 years to learn why some older adults retain unusually sharp cognition.

Emily Rogalski, director of the Healthy Aging & Alzheimer's Research Care Center at the University of Chicago, established the definition of SuperAging in 2008. She said one open question has been whether SuperAgers mainly carry fewer genetic risks tied to Alzheimer's disease.

Do SuperAgers have lower Alzheimer's genetic risk?

The study found no clear genetic advantage that separated SuperAgers from older adults with average cognitive performance, according to the University of Chicago Medical Center. Researchers reported the results in Alzheimer's Research & Therapy.

The research team included scientists from the University of Chicago's HAARC Center and the Translational Genomics Research Institute, or TGen, which is part of City of Hope. They studied 142 SuperAgers and 89 cognitively average older adults recruited from five regional sites in the United States and Canada.

Using DNA from blood samples, the team examined APOE, described by the researchers as the strongest known genetic risk factor for Alzheimer's disease. They also calculated three polygenic risk scores, which combine thousands of genetic variants associated with inherited Alzheimer's risk.

Researchers said APOE and the Alzheimer's polygenic risk scores did not distinguish SuperAgers from the comparison group. They also looked at rare genetic variants previously linked to protection or resilience against Alzheimer's disease and found those variants were not more common among SuperAgers.

What are SuperAgers?

SuperAgers are older adults, often in their 80s or 90s, who show memory abilities more typical of people in their 50s or 60s, according to the University of Chicago Medical Center. The label refers to cognitive performance, not to a single gene, diagnosis or lifestyle pattern.

Ana Capuano, director of the biostatistics core at the HAARC Center and a co-first author, said the findings show that preserving cognitive health involves more than lowering Alzheimer's disease risk. She said studying biological, behavioral and social factors behind exceptional cognitive aging may help shape more personalized ways to support brain health.

Matt Huentelman, a TGen professor and co-senior author with Rogalski, said the work sets a boundary for Alzheimer's genetics. He said common genetic risks captured by APOE and current polygenic risk scores do not explain the SuperAging pattern.

The researchers said future work will take a broader approach. Planned studies will combine cognitive testing with brain imaging, blood biomarkers, genetics, neuropathology, immune profiling, sleep and activity monitoring, and social and environmental measures.

Ignazio S. Piras, a TGen associate professor and co-first author, said the absence of risk factors does not necessarily mean a person has the protective factors that support exceptional brain health. The study, he said, helps demonstrate that distinction.

The work was supported by the National Institute on Aging, the McKnight Brain Research Foundation through the SuperAging Research Initiative, the Simons Foundation and participants and collaborators across the five research sites, according to the University of Chicago Medical Center.

This story draws on original reporting from ScienceDaily.