The First 25 Years of SuperAger Research Reveal Aging Doesn't Mean Cognitive Decline

The Science Behind SuperAgers

For over 25 years, researchers at Northwestern Medicine have been studying a unique group of individuals aged 80 and older—known as "SuperAgers." These individuals exhibit memory performance that is comparable to people who are at least three decades younger, challenging the long-standing belief that cognitive decline is an unavoidable part of aging. This groundbreaking research has provided valuable insights into what makes these individuals so special.

Understanding Cognitive Resilience

The study has revealed several lifestyle and personality differences between SuperAgers and those who age typically. For instance, SuperAgers tend to be more social and gregarious. However, it is the findings related to their brains that have had the most significant impact on the scientific community. Dr. Sandra Weintraub, a professor of psychiatry and behavioral sciences and neurology at Northwestern University Feinberg School of Medicine, emphasized this point.

"Beyond their behaviors, what we've found in their brains has been truly earth-shattering," she said. By identifying biological and behavioral traits associated with SuperAging, scientists hope to develop new strategies to promote cognitive resilience and delay or prevent diseases like Alzheimer's.

A New Perspective on Brain Health

Weintraub, who is the corresponding author of a recent paper summarizing the findings, noted that exceptional memory in old age is not only possible but also linked to a distinct neurobiological profile. This discovery opens the door to new interventions aimed at preserving brain health well into later life.

The paper was published in a perspective piece in Alzheimer's & Dementia, highlighting the significance of the research in the field of cognitive neurology.

The Origins of the SuperAger Concept

The term "SuperAger" was coined by Dr. M. Marsel Mesulam, who established the Mesulam Center for Cognitive Neurology and Alzheimer's Disease at Northwestern in the late 1990s. Since 2000, the center has welcomed a cohort of 290 SuperAger participants. Scientists have conducted autopsies on 77 donated SuperAger brains, some of which contained amyloid and tau proteins—factors known to play key roles in the progression of Alzheimer's disease. However, others did not develop any of these markers.

"We realized there are two mechanisms that lead someone to become a SuperAger," Weintraub explained. "One is resistance: they don't make the plaques and tangles. The second is resilience: they make them, but they don't affect their brains."

Key Findings from the Research

Several key findings have emerged from the study:

• Exceptional Memory Performance: SuperAgers score at least 9 out of 15 on a delayed word recall test, matching the performance of individuals in their 50s and 60s.
• Youthful Brain Structure: Unlike typically aging brains, SuperAgers show no significant thinning of their cortex—the outer layer of the brain. In fact, they often have a thicker anterior cingulate cortex than younger adults. This region is crucial for decision-making, emotion, and motivation.
• Unique Cellular Traits: SuperAgers have more von Economo neurons, which are linked to social behavior, and larger entorhinal neurons, which are critical for memory, compared to their peers.
• Sociability as a Common Trait: Despite diverse lifestyles and varying approaches to exercise, SuperAgers tend to be highly social and report strong interpersonal relationships.

The Importance of Brain Donation

At the Mesulam Center, SuperAgers are evaluated annually and may choose to donate their brains for post-mortem evaluation by Northwestern scientists. This process has been instrumental in uncovering many of the findings presented in the recent paper.

"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."

Looking Ahead

This research provides a foundation for future studies aimed at understanding and promoting cognitive resilience. As scientists continue to explore the factors that contribute to SuperAging, the potential for developing new treatments and interventions to combat cognitive decline becomes increasingly promising. The insights gained from SuperAgers could ultimately benefit millions of people facing the challenges of aging and neurodegenerative diseases.