For 25 years, scientists at Northwestern Medicine have been investigating a remarkable group of individuals known as SuperAgers — people aged 80 and older whose memory functions match those of adults at least 30 years younger. These findings challenge the long-standing belief that significant memory decline is an inevitable part of aging.

The study, which was published as a perspective article in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, was published in conjunction with the journal’s special issue commemorating the 25th anniversary of the National Alzheimer Coordinating Centre and the 40th anniversary of the National Institute on Aging’s Alzheimer’s Disease Centres Program.

“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 Dr. Sandra Weintraub, professor of psychiatry and behavioral sciences and neurology at Northwestern University Feinberg School of Medicine and corresponding author of the new paper.

What Makes a SuperAger?

The term SuperAger was first introduced in the late 1990s by Dr. M. Marsel Mesulam, founder of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern. Since 2000, the center has enrolled 290 SuperAgers in ongoing studies, with 77 brain donations examined after death.

SuperAgers share certain traits:

• Exceptional memory: Scoring at least 9 out of 15 on a delayed word recall test — on par with people in their 50s and 60s.
• Youthful brain structure: Unlike typical aging brains, SuperAgers maintain cortical thickness and even have a thicker anterior cingulate cortex than younger adults.
• Specialized neurons: Higher numbers of von Economo neurons, linked to social behavior, and larger entorhinal neurons, essential for memory.
• Sociability: A consistent pattern of high social engagement and strong relationships, despite varied lifestyles and exercise habits.
  

Resistance and Resilience in the Brain

Post-mortem analysis revealed that some SuperAger brains contained amyloid plaques and tau tangles — hallmark proteins of Alzheimer’s disease — while others did not.

“What we realized is there are two mechanisms that lead someone to become a SuperAger,” said Weintraub. “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.”

This distinction may be key in developing therapies that either prevent these harmful proteins from forming or protect the brain from their effects.

A Unique Opportunity for Scientific Discovery

At the Mesulam Center, SuperAgers undergo annual evaluations and may choose to donate their brains for research.

“Many of the findings from this paper stem from the examination of brain specimens of generous, dedicated SuperAgers who were followed for decades,” said Dr. Tamar Gefen, associate professor of psychiatry and behavioral sciences at Feinberg, director of Feinberg’s Laboratory for Translational Neuropsychology, and 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.”

By identifying the biological and behavioral traits that set SuperAgers apart, scientists aim to develop new strategies to delay or prevent dementia from Alzheimer’s disease, frontotemporal degeneration, and other neurodegenerative disorders.

Original Publication
Journal: Alzheimer s & Dementia
Article Title: THE FIRST 25 YEARS OF THE NORTHWESTERN SUPERAGING PROGRAM
Article Publication Date: 7-Aug-2025