A donated SuperAger brain. Credit: Shane Collins, Northwestern University
Sometimes it can be useful to investigate when things in the brain go right, rather than wrong, to understand human pathologies such as Alzheimer’s and dementia.
Researchers at Northwestern University in the US have been studying “SuperAgers” – adults over the age of 80 who have the memory capacity of individuals at least 3 decades younger – for the past 25 years to better understand what makes their brains so resilient to cognitive decline.
The findings of the SuperAging Program to date have been presented in a new Perspective article in the journal Alzheimer’s & Dementia.
They reveal important insights into the biological and behavioural traits associated with SuperAging.
For example, SuperAgers tend to be highly social, report strong interpersonal relationships, and “relished extracurricular activities”.
But, according to Dr Sandra Weintraub, professor of psychiatry, behavioural sciences and neurology at Northwestern, “it’s really what we’ve found in their brains that’s been so earth-shattering for us”.
“Our findings show that exceptional memory in old age is not only possible but is linked to a distinct neurobiological profile.”
Since 2000, a cohort of 290 SuperAgers has been evaluated annually with blood samples, brain imaging and surveys and questions about memory and other thinking abilities.
This included the Rey Auditory Verbal learning Test (RAVLT), which assesses an individual’s immediate memory and verbal learning.
Participants are given 3 trials to recall as many words as possible from a list of 15 unrelated words and must then recall these words again after a 5 – 25-minute delay.
According to the Perspective, SuperAgers score at least 9 out of 15, which “was average for 56 to 66 years old, but considerably higher than the average for an 80+ year old”.
Neuroimaging revealed that SuperAger brains do not undergo structural changes typically seen in ageing, such as significant thinning of the outermost layer – the cortex.
“Does this result mean that superagers start life with larger brains?” the authors write.
“Because it is not possible to have retroactive brain imaging, the indirect way to address this question is through longitudinal studies. In a preliminary study over 18 months, overall cortical thickness was reduced by 1.06% in superagers compared to 2.24% in neurotypical peers, a difference that was statistically significant.
“It appears that cortical thinning is unavoidable, but that it is probably much slower in superagers. Whether these individuals are also born with larger brains remains to be addressed, but is unlikely to be the entire answer given the absence of obvious differences in skull morphology.”
A scientist at Northwestern University holds a donated SuperAger brain. Credit: Shane Collins, Northwestern University
SuperAgers also have thicker ‘anterior cingulate cortexes’ than younger adults. This region of the brain, according to the authors, “mediates processes related to homeostasis; motivation; emotion; and, most importantly, social networking and affiliative behaviours, factors that resonate with superager characteristics.”
Insight into the cellular traits of SuperAger brains were made possible by 77 participants who choose to donate their brains after death.
Post mortem evaluation revealed that SuperAger brains have more von economo neurons (specialised cells linked to social behaviour) and larger entorhinal neurons, which are critical for memory, than in typically ageing adults.
And, while some SuperAger brains had developed amyloid and tau proteins – also known as plaques and tangles, which are known to play key roles in the progression of Alzheimer’s disease – others didn’t.
“What we realised is there are 2 mechanisms that lead someone to become a SuperAger,” Weintraub says. “One is resistance: they don’t make the plaques and tangles.”
The second is resilience. “They make them, but they don’t do anything to their brains,” says Weintraub.
“This opens the door to new interventions aimed at preserving brain health well into the later decades of life.”