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The Answer to Alzheimer's Could Lie in SuperAgers

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The Answer to Alzheimer's Could Lie in SuperAgers about undefined
When searching for a cure for Alzheimer’s, most scientists look at existing brain degeneration and try to figure out how to fix it. What might we find out if we looked instead at the brains of people with superior brain health? That’s what a group of researchers at the University of Chicago asked themselves.

They chose elderly people with exceptional memories to see why their brains perform so well. Their findings may lead to new strategies to save cognition and uncover new treatments for Alzheimer’s disease.

The term SuperAgers refers to people over the age of 80 whose memories are as good as those folks who are 20 to 30 years their junior. The moniker was coined in 2007 by scientists at the Northwestern Mesulam Center for Cognitive Neurology and Alzheimer's Disease.

To determine the differences between the brains of SuperAgers and other healthy people of the same age, as well as the brains of people with cognitive impairment, researchers have conducted a series of studies.

Their results are impressive to say the least.

SuperAgers Have Larger, Thicker Brains 

In one study, the researchers compared brain scans of 12 SuperAgers with scans of ten cognitively normal people of the same age, and another fourteen people aged 50 to 65.

They found the cingulate cortex, a region important for memory, attention, cognitive control, and motivation, was thicker in SuperAgers than in their same-age peers.

Surprisingly, a small area of the anterior region of the cingulate cortex, which is involved with complex functions such as emotion, empathy, impulse control and decision-making, had greater thickness in SuperAgers than was seen in even their middle-aged counterparts.

Northwestern researchers also discovered that SuperAgers have three to five times the number of von Economo neurons compared to age-matched controls. These are rare, spindle-shaped cells mostly populated in the anterior cingulate cortex. They are linked to social intelligence and awareness. The SuperAgers even had more of these neurons than younger adults had.

In another investigation, the Northwestern team measured changes in brain volume over 18 months. Normal elderly participants saw a 2.24 percent volume loss but SuperAgers lost less than half of that—suffering only a 1.06 percent volume loss.

Then they tested for brain-cell-choking proteins which are linked to Alzheimer's disease.

87 Percent Fewer Tau Tangles 

Tau protein is important for transporting nutrients to nerves and is needed for cell communication. In Alzheimer's disease, tau forms tangles that lead to brain cell death. In fact, tau has long been considered a key marker for dementia, more so than the better known amyloid plaques.

In their post-mortem study, SuperAgers had 87 percent fewer tau tangles in the anterior cingulate cortex than aged-matched controls and 92 percent fewer tangles than those with mild cognitive impairment.

In this post-mortem research, the researchers investigated the extent of amyloid plaque and tau tangle build up in the entorhinal cortex, an area of the brain that's largely responsible for memory. They found SuperAgers had almost three-fold fewer tangles than their aged-matched peers and a hundred times fewer tangles than those people with Alzheimer's.

Lead author Tamar Gefen commented, "The results suggest resistance to age-related tau degeneration in the cortex may be one factor contributing to preserved memory in SuperAgers.

"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."

When it came to amyloid plaques, the SuperAgers had the same density of plaques as the cognitively healthy elderly group. This adds to growing evidence that we’ve long reported in this newsletter that amyloid is not the driver of memory loss.

Taking a Holistic Approach 

Next, Professor Gefen wants to explore genetic, molecular and biochemical factors that may play a role in the brains of SuperAgers, but she’s also interested in environment and lifestyle.

"...we must take their personal narratives (history, proclivities, behaviors, cultures) into account when making conclusions about their unique neuro-anatomic profiles."

I couldn’t agree more. One lifestyle factor that Prof. Geffen and her team have already identified in SuperAgers is resilience. They've discovered SuperAgers have great resilience in the face of stress.

Northwestern team member Dr. Emily Rogalski explained, saying, "We all encounter stress and have the opportunity to react in different ways. One reaction can be to rise above it, and it seems like these SuperAgers are particularly good at really identifying the best in a situation and figuring out how to move on."
  1. https://www.nia.nih.gov/news/cognitive-super-agers-defy-typical-age-related-decline-brainpower
  2. https://news.feinberg.northwestern.edu/2015/02/gefen-superagers/ 
  3. https://news.northwestern.edu/stories/2021/02/superager-brains-alzheimers/ 
  4. https://pubmed.ncbi.nlm.nih.gov/33592091/ 
  5. https://www.feinberg.northwestern.edu/research/news/podcast/what-makes-someone-a-superager.html 

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