Secrets of the Super Agers

March 8, 2021

What keeps someone mentally sharp into their 70s, 80s, 90s and beyond? Researchers at Northwestern University School of Medicine are seeking to find out in an ongoing series of studies of what keeps people cognitively healthy into very old age.

In their latest study, they report that people who remain free of serious memory and thinking problems in old age seem to be resistant to the formation of tau, a distorted protein that builds up in the brains of those with Alzheimer’s disease, forming telltale, spaghetti-like tangles that might choke off healthy neurons. Tau is also one of the top two hallmarks of the disease, the other being a component called beta amyloid that clumps together to form amyloid brain plaques. People who grow old free of memory problems seem to have far less tau buildup than their memory-impaired peers.

Scientists who study Alzheimer’s disease have long observed that tau-filled cells first emerge in a part of the brain called the entorhinal cortex, a sliver of tissue in the center of the brain that is critical for forming memories. As Alzheimer’s progresses, tau spreads through other areas of the brain, leading to worsening problems with thinking and memory.

In the current study, published in the journal Cerebral Cortex, researchers found that men and women older who remained mentally intact into old age — a group that the research team called cognitive SuperAgers — had three-fold fewer tangles in the brain than their peers who were aging normally.

“Individuals with significant memory impairment due to Alzheimer’s disease showed nearly 100 times more tangles in the entorhinal cortex compared to Super Agers,” said lead study author Tamar Gefen, an assistant professor of psychiatry and behavioral sciences at Northwestern. “There is a strong relationship between tau-tangles and memory loss, and these findings in a unique SuperAging cohort could guide research in a new direction.”

“The results suggest resistance to age-related tau degeneration in the cortex may be one factor contributing to preserved memory in SuperAgers,” Dr. Gefen said.

The Northwestern researchers define “Super Agers” as people in their 80s and older who maintain memory skills typical of someone 20 to 30 years younger. They have been studying these individuals for more than a decade, performing annual tests of thinking and memory skills.

Those in the long-running study also undergo regular brain scans to look for signs of tau tangles and beta-amyloid. While tangles and plaques are hallmarks of Alzheimer’s disease, many older people with normal thinking and memory skills have some in their brains as well.

While this study found far fewer tangles in the brains of Super Agers compared to those who were aging normally, there was no significant difference in the numbers of beta-amyloid plaques. “Many investigators have long thought that amyloid plaques are drivers of memory loss, which isn’t what we found”,
 Dr. Gefen said.

The researchers plan follow-up studies to learn more about why brain cells become vulnerable to tangles in the first place, and why people who remain mentally young remain protected from tangle buildup.

Other research from the group has found that Super Agers seem to maintain strong social and family ties and active engagement in work, hobbies and cognitively stimulating activities, all of which have been linked to a reduced risk for Alzheimer’s disease.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University. 

Source: “Paucity of Entorhinal Cortex Pathology of the Alzheimer’s Type in SuperAgers with Superior Memory Performance,” Cerebral Cortex, Feb. 17.


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