SuperAger brains yield new clues to their remarkable memories

February 5, 2015

Three cingulate ROIs. Medial ROIs of the cingulate cortex in the Desikan-Killiany (Desikan et al., 2006) cortical labeling protocol are color-coded with their corresponding parcellations characterized by Vogt (2009) (credit: Tamar Gefen et al./The Journal of Neuroscience)

SuperAgers, aged 80 and above — but with memories that are as sharp as those of healthy persons decades younger — have distinctly different looking brains than those of normal older people, according to new Northwestern Medicine research.

Understanding Superagers’ unique “brain signature” may enable scientists to decipher the genetic or molecular source and develop strategies to protect the memories of normal aging persons, as well as treat dementia.

Published Jan. 28 in the Journal of Neuroscience, the study is the first to quantify brain differences of SuperAgers and normal older people.

Cognitive SuperAgers were first identified in 2007 by scientists at Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center at Northwestern University Feinberg School of Medicine.

A unique brain signature

Their unusual brain signature has three common components when compared with normal persons of similar ages: a thicker region of the cortex; significantly fewer tangles (a primary marker of Alzheimer’s disease), and a whopping supply of a specific neuron — von Economo — linked to higher social intelligence.

Less tangles. Thioflavin-S staining of NFTs and APs at 20x magnification. The photomicrographs above show no (or extremely sparse) Alzheimer neuropathology (APs and NFTs) in the anterior aspects of cingulate cortex (aMCC) in a 90-year-old SuperAger (SuperAger 3) compared with an age-matched elderly control (middle), and an individual diagnosed clinically with aMCI (bottom). Scale bar in bottom left corner indicates 50µm at 20x. (Credit: Tamar Gefen et al./The Journal of Neuroscience)

“The brains of the SuperAgers are either wired differently or have structural differences when compared to normal individuals of the same age,” said Changiz Geula, study senior author and a research professor at the Cognitive Neurology and Alzheimer’s Disease Center.

“It may be one factor, such as expression of a specific gene, or a combination of factors that offers protection.”

“Identifying the factors that contribute to the SuperAgers’ unusual memory capacity may allow us to offer strategies to help the growing population of ‘normal’ elderly maintain their cognitive function and guide future therapies to treat certain dementias,” said Tamar Gefen, the first study author and a clinical neuropsychology doctoral candidate at Feinberg.

MRI imaging

MRI imaging and an analysis of the SuperAger brains after death show the following three brain signatures in the anterior cingulate cortex.

Thicker. MRI imaging showed the anterior cingulate cortex of SuperAgers (31 subjects) was significantly thicker than the same area in aged individuals with normal cognitive performance (21 subjects), and also larger than the same area in a group of much younger, middle-aged individuals (ages 50 to 60, 18 subjects).

This region is indirectly related to memory through its influence on related functions such as cognitive control, executive function, conflict resolution, motivation and perseverance.

Less tangles. Analysis of the brains of five SuperAgers showed the anterior cingulate cortex had approximately 87 percent less tangles than age-matched controls and 92 percent less tangles than individuals with mild cognitive impairment. Neurofibrillary brain tangles, twisted fibers consisting of the protein tau, strangle and eventually kill neurons.

More neurons. The number of von Economo neurons was about three to five times higher in the anterior cingulate of SuperAgers compared with age-matched controls and individuals with mild cognitive impairment.

“It’s thought that these von Economo neurons play a critical role in the rapid transmission of behaviorally relevant information related to social interactions,” Geula said, “which is how they may relate to better memory capacity.” These cells are present in such species as whales, elephants, dolphins and higher apes.

The Cognitive Neurology and Alzheimer’s Disease Center has a new NIH grant to continue the research. The research was funded by National Institute on Aging, National Institutes of Health, The Davee Foundation, a Northwestern University Alzheimer’s Disease Core Center grant from the National Institute on Aging, and a fellowship from the National Institute on Aging.

For more information on the SuperAger study, visit

Abstract of Morphometric and histologic substrates of cingulate integrity in elders with exceptional memory capacity

This human study is based on an established cohort of “SuperAgers,” 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20–30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50–60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.