Background As longevity increases and the population over age 65 expands, advancing age remains the most reliable predictor of cognitive decline, highlighting the need to identify biological mechanisms that support exceptional cognitive aging. We tested whether lower inherited risk of Alzheimer’s disease (AD) dementia predicts SuperAger status (adults ≥ 80 years with episodic memory at least as good as middle-age adults) using prospectively enrolled SuperAgers and Cognitively Average Controls (Controls) from the multisite SuperAging Research Initiative. Methods We studied 231 participants (SuperAgers n = 142; Controls n = 89). We confirmed that the genetic ancestry structure across groups was comparable. We evaluated whether APOE status (ε2, ε3, ε4) and three AD polygenic risk scores (PRS) derived from large contemporary Genome-Wide Association Studies (GWAS) (PRSLambert, PRSWightman, PRSBellenguez) predicted SuperAging status using logistic regression models adjusted for age, sex, and education, considering ancestry interactions. Results APOE allele and genotype distributions did not differ between groups, and neither APOE nor any of the three PRS predicted SuperAger status. Results were unchanged when accounting for global non-European or African ancestry or principal components. In this well-characterized cohort, neither APOE nor contemporary PRS explained SuperAger status. Conclusions These findings suggest that the exceptional late-life memory phenotype that is characteristic of SuperAging is not explained by common-variant AD genetic risk captured by APOE or contemporary AD PRS, motivating a deeper investigation of potential rare genetic variations and experiential factors contributing to exceptional cognitive aging.

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YouTube video by Wallenbergstiftelserna

People who live past 100 have surprising abundance of cancer-killing immune cells, according to new research published in Cell Press revealing superager secrets. Rare few people will see 100th birthda...

Superagers maintain exceptional memory by growing new hippocampal neurons at twice the rate of their peers.

Background As longevity increases and the population over age 65 expands, advancing age remains the most reliable predictor of cognitive decline, highlighting the need to identify biological mechanisms that support exceptional cognitive aging. We tested whether lower inherited risk of Alzheimer’s disease (AD) dementia predicts SuperAger status (adults ≥ 80 years with episodic memory at least as good as middle-age adults) using prospectively enrolled SuperAgers and Cognitively Average Controls (Controls) from the multisite SuperAging Research Initiative. Methods We studied 231 participants (SuperAgers n = 142; Controls n = 89). We confirmed that the genetic ancestry structure across groups was comparable. We evaluated whether APOE status (ε2, ε3, ε4) and three AD polygenic risk scores (PRS) derived from large contemporary Genome-Wide Association Studies (GWAS) (PRSLambert, PRSWightman, PRSBellenguez) predicted SuperAging status using logistic regression models adjusted for age, sex, and education, considering ancestry interactions. Results APOE allele and genotype distributions did not differ between groups, and neither APOE nor any of the three PRS predicted SuperAger status. Results were unchanged when accounting for global non-European or African ancestry or principal components. In this well-characterized cohort, neither APOE nor contemporary PRS explained SuperAger status. Conclusions These findings suggest that the exceptional late-life memory phenotype that is characteristic of SuperAging is not explained by common-variant AD genetic risk captured by APOE or contemporary AD PRS, motivating a deeper investigation of potential rare genetic variations and experiential factors contributing to exceptional cognitive aging.

Neue Forschungsergebnisse zeigen: Kognitive Resilienz bei Hochbetagten hängt stärker von Lebensstil und sozialen Faktoren ab als von der Genetik.

Some 80-year-olds' cognitive functioning rivals those 30 years younger. The Northwestern SuperAging program releases insights from its first 25 years that offer clues as to why.

Exceptional memory in later life may depend less on inherited Alzheimer's risk and more on the biological and lifestyle factors that help some older adults stay cognitively sharp for decades. Study: SuperAging is not the inverse of common-variant Alzheimer’s risk: evidence across genetic ancestries. Image credit: fizkes/Shutterstock.com A new study published in the journal Alzheimer's Research & Therapy found that exceptional memory in SuperAgers, older adults who maintain unusually strong memory into their 80s and 90s, is not explained simply by lower inherited genetic risk for Alzheimer's disease (AD). Testing whether genetics explains SuperAging Age is the strongest predictor of cognitive decline, but the underlying mechanisms remain unclear. Cognitive decline is characterized by declining episodic memory and changes in hippocampal and cortical circuits key to memory. Notably, SuperAgers continue to have exceptional episodic memory well into their eighties, performing at levels comparable to those of adults several decades younger, which could help clarify how memory functions are preserved in late life. Common genetic risk for AD is most commonly assessed using APOE status and AD polygenic risk scores (PRSs), which capture the cumulative effects of thousands of common genetic variants associated with the condition. APOE is the strongest common genetic...

A study on SuperAgers shows exceptional memory isn't solely due to lower Alzheimer's genetic risk, highlighting the role of biological and lifestyle factors.

Researchers have spent decades studying the rare people whose memory stays decades younger than their age. Their biggest lessons have little to do with supplements and everything to do with how they live.

Researchers have spent decades studying the rare people whose memory stays decades younger than their age. Their biggest lessons have little to do with supplements and everything to do with how they live.

Researchers have spent decades studying the rare people whose memory stays decades younger than their age. Their biggest lessons have little to do with supplements and everything to do with how they live.

Dr. Alan Castel (UCLA) reveals the science of memory: how to boost recall, beat false memories, and become a 'superager' who improves with age.

Neurologist Emily Rogalski studies "superagers" – people in their 80s or 90s with unusually keen memories, whose lifestyles suggest ways to slow cognitive decline