The distinct pathophysiology of ‘SuperAger’ brains

The Northwestern University Feinberg School of Medicine Mesulam Center for Cognitive Neurology and Alzheimer’s Disease is currently recruiting participants to be part of their ‘SuperAging Research Program.’ Data collected from current and previous SuperAgers have provided new and exciting insights into how the brains of these individuals compare to those of otherwise healthy adults, as well as those diagnosed with Alzheimer’s disease, to better understand the neurological processes associated with aging.

Studying SuperAgers is important to understand what is going right with aging, as opposed to what is going wrong."

Image Credit: pikselstock /

Image Credit: pikselstock /

What is a SuperAger?

The term ‘Superagers,’ as defined by Northwestern researchers, reflects adults over the age of 80 who have a superior memory capacity that resembles that of middle-aged adults. In order to be accepted into the program, this group of elderly individuals must demonstrate that their ability to recall everyday events and previous personal experiences is significantly better than people in their 50s and 60s; however, their performance on other cognitive tests does not necessarily need to be superior.

Why study SuperAgers?

In addition to gaining a better understanding of how different aging processes are reflected in the brain, Northwestern researchers also believe that data obtained from the SuperAging study will have significant implications for elucidating the mechanisms responsible for the development of Alzheimer’s disease and dementia.

One way to study [dementia and Alzheimer’s disease] is to look at what’s going wrong with the brain and then try to fix or ameliorate or find a cure for what’s going wrong there…sometimes it’s really helpful to turn it on its head and look from a different vantage point or perspective.”

The SuperAger brain

In the SuperAging program, study participants provide blood samples, as well as magnetic resonance imaging (MRI) and/or positron-emitted tomography (PET) scans of their brains, in addition to participating in memory and other cognitive assessments.

Furthermore, after a SuperAger dies, they donate their brains to the SuperAging program. To date, the brains of deceased SuperAgers have revealed relatively thick cortexes that shrink at a much slower rate as compared to individuals in their 50s and 60s. The cortex is responsible for decision-making processes, critical thinking, and retention and memories.

Northwestern researchers believe that the delayed shrinking in the SuperAger’s brain may be due to larger and healthier neurons, particularly within the entorhinal cortex. The entorhinal cortex, which is often the first area of the brain to be affected in Alzheimer’s disease, plays an important role in both memory and learning, particularly due to its interactions with the hippocampus.

In addition to a more resilient cortex, SuperAger brains also appear to have significantly fewer tau tangles as compared to healthy controls. This abnormal protein accumulation within neurons is often indicative of Alzheimer’s disease; therefore, the reduced concentration of tau tangles within the SuperAger brain may be related to their more robust cortex that is capable of withstanding damage by tau protein infiltration.

The von Economo neurons (VENs), which are located in both the fronto-insular cortex (FI) and anterior limbic area (LA) of the brain, are elongated bipolar neurons that are not commonly found in many species aside from humans, apes, elephants, whales, dolphins, and songbirds. Although the functional implications of VENs remain unclear, previous studies indicate that the abundance of these nerve cells within the anterior cingulate cortex likely indicates that they are important for regulating emotions and attentiveness.

Interestingly, the brains of SuperAgers exhibit a significantly greater concentration of VENs.

Daily activities of SuperAgers

Despite the vast difference in the backgrounds, education levels, and personal experiences of the SuperAgers, they share several key similarities in how they spend most of their days.

Most SuperAgers appear to remain relatively active on a daily basis. In addition to being physically active, these individuals also constantly use their brains every day, either through reading, learning something new, or continuing to work well into their 80s.

SuperAgers also appear to be more social, with many often surrounded by family and friends, in addition to being active volunteers within their community. This strong sense of connection to others appears to be a distinguishing feature among SuperAgers as compared to otherwise healthy individuals of the same age.  

Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine; two nitrogen mustard alkylating agents that are used in anticancer therapy.


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