Summary: For 25 years, researchers at Northwestern Medicine have studied a rare group of people aged 80 and older—called “SuperAgers”—whose memory and cognitive abilities match those of people decades younger. Findings show that some SuperAgers avoid the plaques and tangles associated with Alzheimer’s disease, while others tolerate those changes without losing cognitive function.
These individuals preserve a more youthful brain anatomy, including a thicker cortex and distinctive neurons tied to memory and social behavior. Understanding the biological and behavioral traits of SuperAgers may point to new ways to protect cognitive health and extend mental vitality into advanced age.
Key Facts
- Exceptional memory: SuperAgers score on delayed recall tests at levels typical of people in their 50s and 60s despite being 80 or older.
- Preserved brain structure: Their brains show less cortical thinning and, in some regions, greater thickness than expected for their age.
- Protection mechanisms: Some SuperAgers appear resistant to Alzheimer’s pathology; others display resilience, maintaining function despite pathology.
Source: Northwestern University
Background: For a quarter century, scientists at Northwestern Medicine have followed people aged 80 and up who demonstrate unusually strong memory and cognitive performance. Dubbed “SuperAgers,” these volunteers challenge the assumption that cognitive decline is an unavoidable part of aging.
Over decades of study, researchers have noted lifestyle and personality features that often accompany SuperAging—among them strong social engagement and outgoing personalities—but the most striking discoveries have come from examining the brain itself. “It’s really what we’ve found in their brains that’s been so earth-shattering for us,” said Dr. Sandra Weintraub, professor of psychiatry and behavioral sciences and neurology at Northwestern University Feinberg School of Medicine.
The research aims to identify biological and behavioral markers that support lifelong cognitive resilience, with the ultimate goal of developing interventions that might delay, prevent, or reduce the impact of Alzheimer’s disease and other causes of dementia.
“Our findings show that exceptional memory in old age is not only possible but is linked to a distinct neurobiological profile,” Weintraub said. “This opens the door to new interventions aimed at preserving brain health well into the later decades of life.” The findings are summarized in a perspective paper prepared for a special journal 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.
Resistance and resilience in SuperAger brains
The label “SuperAger” was introduced by Dr. M. Marsel Mesulam when he founded the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern in the late 1990s. Since 2000, the center has worked with a cohort of SuperAgers and performed post-mortem examinations on many donated brains. Among the brains examined, some showed amyloid and tau changes—plaques and tangles linked to Alzheimer’s—while others showed few or none.
Researchers have identified two distinct ways people become SuperAgers: resistance, in which individuals do not develop the plaques and tangles, and resilience, where individuals do develop those pathologies but their brains remain functionally intact despite them.
Other key findings
- Memory testing: SuperAgers commonly achieve scores of 9 or higher out of 15 on delayed word recall tests—scores comparable to people 20–30 years younger.
- Youthful cortical anatomy: Unlike typical age-related shrinkage, SuperAgers show preserved cortical volume and, in some areas such as the anterior cingulate cortex, even greater thickness than younger adults. This region supports decision-making, emotion, and motivation.
- Distinct cellular features: Compared with typical older adults, SuperAgers often have more von Economo neurons—cells associated with social behavior—and larger entorhinal neurons that are important for memory.
- Social engagement: Although their lifestyles vary, SuperAgers frequently report strong social connections and active interpersonal lives.
Brain donation and long-term discovery
Participants at the Mesulam Center are evaluated annually and may choose to donate their brains after death for scientific study. Many of the program’s most important discoveries came from these donated specimens, which allowed researchers to link lifelong clinical data with direct measures of brain pathology.
“Brain donation can enable discovery long after death, offering a kind of scientific immortality,” said co-author Dr. Tamar Gefen, associate professor of psychiatry and behavioral sciences and director of Feinberg’s Laboratory for Translational Neuropsychology.
The perspective summarizing the program’s work is titled “The First 25 Years of the Northwestern SuperAging Program.” Authors include Dr. Weintraub, Dr. Mesulam, Changiz Geula, and other Northwestern collaborators.
About this aging and memory research news
Author: Kristin Samuelson
Source: Northwestern University
Contact: Kristin Samuelson, Northwestern University
Image credit: Neuroscience News
Original research (open access): “The First 25 Years of the Northwestern SuperAging Program” by Sandra Weintraub et al., published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Abstract
The First 25 Years of the Northwestern SuperAging Program
Average test scores in late life do not imply preserved cognition. For example, a common word-list test shows an average delayed recall raw score of about 5 out of 15 at age 80, versus about 9 out of 15 in people aged 56–66. That pattern has led to the expectation that cognitive and neurobiological decline are inherent to aging.
Research on “superaging,” a term coined at the Northwestern Alzheimer’s Disease Research Center, challenges that expectation. Superagers are defined as individuals aged 80 or older whose delayed word recall scores are at least as high as those of people 20–30 years younger.
Over 25 years, the program has shown that SuperAgers represent a distinct neuropsychological and neurobiological phenotype. Structurally, SuperAger brains retain cortical volumes comparable to adults 20–30 years younger and, in some regions, show increased thickness. At the cellular level, SuperAgers often exhibit fewer Alzheimer’s-type changes, larger entorhinal neurons, reduced inflammatory microglial activity in white matter, better-preserved cholinergic innervation, and a higher density of von Economo neurons.
Further characterizing the SuperAger phenotype could guide interventions that promote resistance and resilience against brain changes commonly labeled as “normal” aging, reshaping how we think about cognitive potential in late life and inspiring research worldwide.