August 2025

NEUROSCIENCES

WHAT MAKES A SUPERAGER?

Featuring: Sandra Weintraub, PhD

Twenty-five years of SuperAger research show cognitive decline is not an inevitable part of aging

For 25 years, scientists at Northwestern Medicine have been studying individuals aged 80 and older — dubbed “SuperAgers” — to better understand what makes them tick.

These unique individuals, who show outstanding memory performance at a level consistent with individuals who are at least three decades younger, challenge the long-held belief that cognitive decline is an inevitable part of aging.

Over the quarter-century of research, the scientists have seen some notable lifestyle and personality differences between SuperAgers and those aging typically — such as being social and gregarious — but “it’s really what we’ve found in their brains that’s been so earth-shattering for us,” said Sandra Weintraub, PhD, professor of Psychiatry and Behavioral Sciences and of Neurology at Northwestern University Feinberg School of Medicine.

By identifying biological and behavioral traits associated with SuperAging, the scientists hope to uncover new strategies to promote cognitive resilience and delay or prevent Alzheimer’s and other diseases that cause cognitive decline and dementia.

“Our findings show that exceptional memory in old age is not only possible but is linked to a distinct neurobiological profile. This opens the door to new interventions aimed at preserving brain health well into the later decades of life,” said Weintraub, corresponding author of a new paper summarizing the findings.

The paper will be published in a perspective piece in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association as part of the journal’s special issue commemorating the 40th anniversary of the National Institute on Aging’s Alzheimer’s Disease Centers Program and the 25th anniversary of the National Alzheimer Coordinating Center.
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​SuperAger brains are resilient, resistant

The term “SuperAger” was coined by M. Marsel Mesulam, MD, who founded the Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease at Northwestern in the late 1990s.

Since 2000, a cohort of 290 SuperAger participants has passed through the Mesulam Center’s doors, and the scientists have autopsied 79 donated SuperAger brains. Some of the brains contained amyloid and tau proteins (also known as plaques and tangles), which are known to play key roles in the progression of Alzheimer’s disease, but others didn’t develop any.

“What we realized is there are two mechanisms that lead someone to become a SuperAger,” Weintraub said. “One is resistance: they don’t make the plaques and tangles. Two is resilience: they make them, but they don’t do anything to their brains.”

Other key findings:

  • Exceptional memory performance: SuperAgers score at least 9 out of 15 on a delayed word recall test — on par with individuals in their 50s and 60s.
  • Youthful brain structure: Unlike typically aging brains, SuperAgers show no significant thinning of their cortex — the outer layer of the brain — and even have a thicker anterior cingulate cortex than younger adults. This crucial region of the brain plays a significant role in integrating information related to decision-making, emotion and motivation.
  • Unique cellular traits: SuperAgers have more von economo neurons, which are specialized cells linked to social behavior, and larger entorhinal neurons, which are critical for memory, than their typically aging peers.
  • Sociability as a common trait: Despite having diverse lifestyles and varying approaches to exercise, SuperAgers tend to be highly social and report strong interpersonal relationships.

‘Brain donation can offer scientific immortality’
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​At the Mesulam Center, SuperAgers are evaluated annually and may choose to donate their brains for post-mortem evaluation by Northwestern scientists.

“Many of the findings from this paper stem from the examination of brain specimens of generous, dedicated SuperAgers who were followed for decades,” said co-author Dr. Tamar Gefen, associate professor of psychiatry and behavioral sciences at Feinberg, director of Feinberg’s Laboratory for Translational Neuropsychology and a neuropsychologist at the Mesulam Center. “I am constantly amazed by how brain donation can enable discovery long after death, offering a kind of scientific immortality.” 

Learn more about how to join the SuperAger research registry.

The perspective piece is titled, “The First 25 Years of the Northwestern SuperAging Program.” Other Northwestern authors include Mesulam and Changiz Geula, PhD, research professor of Cell and Developmental Biology and a member of the Mesulam Center.

​Over 25 years, the following grants supported varying aspects of the work reported in this paper:

Northwestern Alzheimer’s Disease Research Center (grants 5P30AG072977 and P30AG013854) and the National Institute on Aging (grants R01 – 5R01AG067781 U19 – 5U19AG073153) of the National Institutes of Health.

​This article was originally published in the Northwestern Medicine Newsroom on August 12, 2025. 
Sandra Weintraub, PhD, ​professor of Psychiatry and Behavioral Sciences (Psychology) and Neurology at Northwestern Medicine

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