For a quarter of a century, researchers have been tracking a rare group of older adults who defy expectations about aging. These “SuperAgers,” all aged 80 or older, seem to have brains that age more slowly while routinely scoring very high on memory tests – as well as people three decades younger.
Their performance upends the notion that cognitive decline is an unavoidable consequence of growing old – and it’s giving scientists a roadmap to protect brain health deep into later life.
Studying SuperAgers’ brains
The SuperAging program began in the late 1990s, when neurologist M. Marsel Mesulam coined the term and launched an effort to find out what sets these individuals apart.
Since 2000, 290 SuperAgers have enrolled, and 77 have donated their brains for study after death. The research blends years of cognitive testing, personality assessments, and high-resolution imaging with painstaking postmortem analyses.
Along the way, researchers noticed a common thread among the living participants.
Many are unusually social and outgoing, reporting rich interpersonal networks and frequent engagement with others. But the most startling insights have come from the tissue under the microscope.
“It’s really what we’ve found in their brains that’s been so earth-shattering for us,” said Sandra Weintraub, a professor of psychiatry, behavioral sciences, and neurology at Northwestern University Feinberg School of Medicine.
What protects SuperAgers’ brains
The pathology tells a nuanced story. Some SuperAger brains show very little buildup of amyloid plaques and tau tangles the proteins that hallmark Alzheimer’s disease. Others carry these lesions but appear unfazed by them.
“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.”
That “do nothing” is key. In typical aging, higher levels of amyloid and tau correlate with cortical thinning and memory decline.
In SuperAgers, either the proteins are absent, or the brain’s networks seem to withstand their presence without measurable loss in function.
This split – resistance versus resilience – could guide both preventive strategies and future treatments for Alzheimer’s and related dementias.
Memory that stays decades younger
In the lab, SuperAgers clear a high bar. On a standard delayed word recall test, they score nine or better out of 15, a performance that mirrors average results for people in their 50s and 60s.
The difference isn’t a fleeting testing trick; it persists year after year in longitudinal follow-up. That consistency allows scientists to distinguish a single lucky test day from a truly exceptional memory profile.
Stronger cortex, sharper memory
Brain imaging adds another layer. Unlike typical older adults, SuperAgers do not show the widespread thinning of the cerebral cortex that comes with age.
In some regions they look even more robust than younger people. The anterior cingulate cortex – central to decision-making, motivation, and emotional control – often appears thicker in SuperAgers than in adults decades their junior.
That pattern hints at why their attention, motivation, and executive function remain so strong and may contribute directly to memory performance.
Cells of connection and strength
Under the microscope, two cellular details stand out. First, SuperAgers have more von Economo neurons – large, fast-signaling cells linked to social behavior and intuition – than typically aging peers.
Second, they show larger neurons in the entorhinal cortex, a hub for memory processing that’s among the first brain regions to falter in Alzheimer’s. Both traits suggest a structural and cellular foundation for the resilience seen at the systems level.
The social theme that emerges in personality measures may not be incidental. More von Economo neurons could be part of the biological substrate underpinning the sociability many SuperAgers report, a behavioral pattern long associated with better cognitive outcomes.
Protecting memory before decline
Weintraub and her colleagues see these findings as more than a scientific curiosity.
“Our findings show that exceptional memory in old age is not only possible but is linked to a distinct neurobiological profile,” she said. “This opens the door to new interventions aimed at preserving brain health well into the later decades of life.”
If researchers can mimic the protective features of SuperAger brains – or train the brain to resist or withstand pathology – clinical practice could shift from chasing symptoms to preserving function.
That may mean new pharmaceuticals aimed at bolstering neural networks, lifestyle interventions that amplify the brain’s natural “reserve,” or a combination of both.
It also reframes traditional Alzheimer’s research: rather than asking only how to remove amyloid or tau, scientists can also ask how to make the brain less vulnerable to them.
SuperAgers’ lasting legacy
Much of what we know comes from an extraordinary commitment by participants. SuperAgers are evaluated annually, and many choose to donate their brains for postmortem analysis.
“Many of the findings from this paper stem from the examination of brain specimens of generous, dedicated SuperAgers who were followed for decades,” said neuropsychologist Tamar Gefen, a co-author on the paper.
“I am constantly amazed by how brain donation can enable discovery long after death, offering a kind of scientific immortality.”
SuperAgers, sharp brains, future health
The team is now probing why some brains resist pathology while others absorb it without consequence. Are there genetic signatures that predict resilience?
Do lifelong habits – social engagement, aerobic fitness, sleep, cognitive challenge – interact with biology to produce the SuperAger profile? And can targeted interventions in midlife shift the brain toward the same protective patterns?
After 25 years, one message is already clear: cognitive decline isn’t a foregone conclusion.
A subset of older adults retains memory performance on par with people decades younger, supported by unusual structural, cellular, and pathological profiles.
SuperAgers show that the aging brain can be both tough and flexible – and that translating their biology into prevention could help more of us keep our minds keen well into our 80s and beyond.
The study is published in the journal Alzheimer’s & Dementia.
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