For more than 25 years, researchers at Northwestern Medicine have been studying people age 80 and older known as "SuperAgers" to understand how some individuals maintain exceptional mental sharpness late in life.
These individuals consistently perform on memory tests at levels similar to people at least 30 years younger, challenging the long-standing belief that cognitive decline is unavoidable with age.
Over decades of research, scientists have noticed some lifestyle and personality traits that set SuperAgers apart from their peers, including being highly social and outgoing. Still, the most surprising discoveries have come from examining their brains. "It's really what we've found in their brains that's been so earth-shattering for us," said Dr. Sandra Weintraub, a professor of psychiatry and behavioral sciences and neurology at Northwestern University Feinberg School of Medicine.
By identifying both biological and behavioral patterns linked to SuperAging, researchers hope to develop new approaches to strengthen cognitive resilience and reduce the risk of Alzheimer's disease and other forms of 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 results.
The findings were published as a perspective article in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, part of a special issue marking 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.
Resilient and Resistant Brains
The label "SuperAger" was introduced by Dr. M. Marsel Mesulam, who founded the Mesulam Center for Cognitive Neurology and Alzheimer's Disease at Northwestern in the late 1990s.
Since 2000, 290 participants have taken part in the program, and researchers have studied 77 donated SuperAger brains after death. Some of these brains showed the presence of amyloid and tau proteins (also known as plaques and tangles), which are strongly linked to Alzheimer's disease. Others showed no signs of these harmful proteins at all.
"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."
Key Discoveries About SuperAgers
Researchers have uncovered several defining characteristics that help explain why SuperAgers maintain such strong cognitive abilities:
- Exceptional memory performance: SuperAgers score at least 9 out of 15 on delayed word recall tests, matching the performance of people in their 50s and 60s.
- Youthful brain structure: Unlike typical aging brains, they show little to no thinning of the cortex, the brain's outer layer. In some cases, a region called the anterior cingulate cortex is even thicker than in younger adults, supporting decision-making, emotion, and motivation.
- Unique cellular features: SuperAgers have a higher number of von economo neurons, which are linked to social behavior, along with larger entorhinal neurons that play a critical role in memory.
- Strong social connections: While their exercise habits and lifestyles vary, most SuperAgers are highly social and maintain close relationships.
Brain Donation and Long-Term Discovery
At the Mesulam Center, participants are evaluated each year and can choose to donate their brains for scientific study after death. These donations have been essential to many of the program's most important findings.
"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."
A Landmark Study on SuperAging
The research is detailed in a perspective article titled "The First 25 Years of the Northwestern SuperAging Program." Additional contributors include Dr. Mesulam and Changiz Geula, a research professor of cell and developmental biology and neuroscience at Feinberg and a member of the Mesulam Center.
Researchers hope these findings will guide future strategies to protect brain health and help more people maintain sharp thinking well into old age.
Key Points
- SuperAgers are people over 80 with remarkably sharp memory, performing as well as individuals at least 30 years younger.
- They tend to be very social and mentally engaged, and their brains show an ability to resist the buildup of Alzheimer's-related plaques and tangles.
- Scientists believe these insights could transform brain health research, leading to new ways to delay or prevent dementia linked to diseases such as Alzheimer's and frontotemporal degeneration.



