For decades, memory decline was considered an inevitable consequence of aging. However, emerging evidence shows that a small subset of older adults — so-called superagers — stay cognitively sharp well into their 80s and 90s.

Research groups worldwide are now investigating the mechanisms underlying super-aging, with the aim of identifying factors that could inform interventions to preserve cognitive function and promote healthier aging across the broader population.

What’s at stake extends beyond curiosity about an exceptional few. By identifying the biological, behavioral, and environmental factors that protect superagers’ brains, scientists hope to uncover strategies to help preserve cognitive function in the broader population of aging adults.

One initiative is Northwestern University’s SuperAging Program. Now in its 25thyear, the program defines superagers as people aged 80 years or older whose memory performance equals or exceeds that of individuals 20-30 years younger.

To qualify as superagers, individuals must score at least 9 out of 15 on a standard word-recall test — a performance typical of adults in their 50s or 60s but well above the average of about five words for those older than 80 years. In addition, their performance on other cognitive domains must be at least age appropriate.

Only about 10% of otherwise healthy older adults meet these stringent criteria, Sandra Weintraub, PhD; M-Marsel Mesulam, MD; and other core members of the Northwestern program noted in a recent perspective article in Alzheimer’s & Dementia.

Is Lifestyle a Factor?

There appears to be no particular lifestyle conducive to super-aging. “Some superagers appeared to follow all conceivable recommendations for a healthy life. Others did not eat well, enjoyed smoking and drinking, shunned exercise, suffered stressful life situations, and did not sleep well. Superagers also did not seem to be medically healthier than their peers,” the Northwestern team reported.

Amanda Cook Maher, PhD, clinical neuropsychologist, who works with superagers at the University of Michigan, Ann Arbor, Michigan, and Michigan Medicine, found that healthy social relationships may be one potential factor.

“Superagers report a higher degree of warm, trusting, positive relationships with others compared to their cognitively average, similar age peers,” Maher told Medscape Medical News.

“Anecdotally, superagers are remarkable and just so much fun,” she noted. “They are so full of life, and their energy and excitement is contagious. Their schedules are jam-packed with volunteering, classes, social engagements, some are still working. It can be challenging to get them in for study visits,” she said.

“While much of the cognitive aging space is focused on what’s going wrong for older adults, the study of superagers allows us to dive into what can go right in the aging brain,” Maher added.

What Does Brain Imaging Show?

Brain scans have revealed significant differences between superagers and their age-matched cognitively average peers.

While typical older adults show widespread cortical thinning compared with younger adults, superagers retain cortical thickness comparable to individuals in midlife.

In particular, the anterior cingulate cortex is typically thicker in superagers than in younger adults. This region supports attention, motivation, and social engagement, echoing behavioral traits seen in superagers, who often report strong social connections and high extraversion.

Superagers show a “striking preservation of the core brain circuit for episodic memory, including hippocampus, entorhinal cortex, and cholinergic basal forebrain, relative to closely matched healthy older adults,” Bryan Strange, MBBS, PhD, director of the Laboratory for Clinical Neuroscience, Polytechnic University of Madrid, Madrid, Spain, told Medscape Medical News.

His research showed that longitudinally, these brain regions, which control memory, expressed a slower rate of atrophy in superagers relative to control individuals, “meaning that the cross-sectional differences could not be simply explained by bigger memory areas at birth,” Strange noted.

Strikingly, superagers also show more volume in areas of the thalamus involved in movement.

“This stuck out like a sore thumb, and at first we weren’t sure how to interpret it,” Strange said. But a machine learning analysis, including a large number of variables to discriminate superagers from control individuals showed that one of the top predictors was movement speed — superagers move more quickly than age-matched control individuals.

Interestingly, the other top predictor was mental health, with superagers showing markedly lower levels of anxiety and depression on clinical scales, Strange noted.

What Neuropathology Reveals

Postmortem studies have identified several distinctive features of superager brains. Notably, they possess a higher density of von Economo neurons — particularly in the anterior cingulate cortex — cells that are linked to social and emotional processing.

Superager brains also have fewer neurofibrillary tangles, the tau aggregates characteristic of Alzheimer’s disease, along with larger entorhinal neurons which are more resistant to neurodegeneration. They show better preservation of the basal forebrain cholinergic system, which supports attention and memory, and reduced microglial-mediated inflammation in white matter.

What Questions Remain?

Despite a growing understanding of superagers, many questions remain.

For example, are they born with protective brain features, or do these features emerge over time? Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?

“I wish there was a simple nature/nurture type of answer to this question. Sadly, there is not,” said Maher.

Another key question is what role genetics and genetic variants play in promoting cognitive resilience.

Maher noted that superagers do not appear to be at particularly low risk of developing Alzheimer’s disease compared with their cognitively normal peers.

“APOE allele profiles are similar in superagers and cognitively normal controls and initial investigation of Alzheimer’s disease polygenic risk scores are also similar in superagers compared to cognitively average controls,” she noted.

On the other hand, Strange said he is “quite convinced” that the superager phenotype has an important genetic component.

In his work with superagers, Strange said he was also struck by the fact that they were more likely to have a musical background than control individuals.

“Our machine learning analysis to predict superager status included 89 variables spanning demographic, neuropsychology, diet, exercise, sleep, personal and socioeconomic status, midlife activities, medical history, and medical and mental health assessments. Despite this wealth of information, the model only reached a discrimination accuracy of 66%, which is not great. This makes me think that there may be other, particularly genetic, variables that would improve discrimination accuracy,” Strange said.

Other open questions include whether targeted interventions could replicate the superaging trajectory in the wider population; and whether social and psychological traits, like gregariousness and engagement, actively contribute to sustaining memory in late life.

“There are likely multiple paths to becoming a superager,” said Maher.

She added that ongoing studies are using wearable sensors in fully remote protocols to track the daily behaviors of superagers. These approaches, she said, will provide objective measures of sleep and activity patterns to complement self-reported data.

Strange said there are modifiable “variables that could be optimized to help individuals reach superager status,” said Strange.

“These include enjoying an active midlife, doing physical exercise, placing an emphasis on good mental health, and keeping a close eye on cardiovascular risk factors [such as] hypertension and hyperglycemia,” he said.