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Retaining Strong Brains in Old Age

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Researchers are exploring several theories to explain why some people’s cognitive abilities
stay intact to the end of life
. Perhaps they start out in life with larger, stronger brains.
Or perhaps their brains somehow change to compensate for aging’s damaging effects. Another
theory being pursued is whether their brains have stronger defenses against the assaults of aging.

A person’s environment

may be a factor. Human and animal studies by NIA-supported scientists have
contributed to the growing body of evidence that enriching experiences, such as advanced education
and mind-challenging occupations, can help brains last longer.
“Various exposures throughout the lifetime might help people maintain their brains better or maintain
their cognition in the face of age- or disease-related brain changes,” explained Yaakov Stern, Ph.D.,
of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University
Medical College, New York.
Other research focuses on

genetic explanations

. In an ongoing study of the Longevity Genes Project
at Albert Einstein College of Medicine, New York, investigators are comparing the genetic profiles
of children of healthy centenarians with the genetic profiles of the children of parents who did
not live as long. They are looking for genes that might support strong neural networks and offer
protection against mental and physical decline.

Social factors

also could play a role in healthy cognitive aging. In one of Northwestern University’s
studies, investigators gave a 42-item questionnaire on psychological well-being to 31 cognitive
super agers and 19 cognitively normal peers. The cognitive super agers reported more friends and
family connections, a finding that builds on past research showing links between psychological
well-being and lower risk of Alzheimer’s. Cognitive Reserve and Brain Maintenance


and why other people’s brains show physical signs of age- and disease-related deterioration
yet continue to function well. Two theories that are being explored revolve around the
concepts of

“cognitive reserve”


“brain maintenance.”

Cognitive reserve is the idea
that some brains are strong enough to fend off the assaults of aging and disease. Brain
maintenance is the idea that some brains have extra power to keep working well even in
the face of aging and disease.

As UC Irvine’s Claudia Kawas, M.D., explained, “You can super age by not getting Alzheimer’s
pathology, or you can super age by getting it and somehow managing to not get sick with it.”

Yaakov Stern, Ph.D., of Columbia University, uses a computer analogy: Some people’s brains have
good hardware that doesn’t break down as easily, while others have software that can write
around problem areas in the hardware.
Rodents are Stars in Aging Brain Research
What specific changes in the brain and body provoke cognitive decline or, conversely, stave it off?
A team of scientists in NIA’s Intramural Research Program, led by Peter Rapp, Ph.D., chief of the
Neurocognitive Aging Section, is seeking an answer through a project called STARRRS, for Successful
Trajectories of Aging: Reserve and Resilience in RatS.


because they are short-lived, and their brains
do not accumulate the hallmark plaque and tangle pathology of Alzheimer’s. The breed of rats used
for STARRRS has natural variability; some maintain their cognitive function as they age, and
some don’t. This makes them particularly useful for comparative studies.
Researchers are observing the behaviors of these rats over their lifetimes and using neuroimaging,
tissue sampling (obtained through noninvasive means, so as not to interfere with behavior), and
other methods to track what’s going on in the brain.
“This is a rare and wonderful opportunity to follow individual animals and relate any changes
in cognitive performance to changes going on elsewhere in the body and in the brain,” said Wagster.
“STARRS should give us insights into potential targets for prevention and intervention,
as well as when it would be most appropriate to intervene.”


In April 2017, NIA coordinated the Cognitive Aging Summit III, which was supported by the
McKnight Brain Research Foundation (MBRF) through a generous grant to the Foundation
for NIH (FNIH). The summit brought together a multidisciplinary group of investigators
with shared interest in research on age-related cognitive decline and cognitive reserve
and resilience, as compared to cognitive impairment or dementia. Participants
identified opportunities for expanding our knowledge in this area, as well as
gaps in our knowledge. One of the opportunities highlighted resulted in the
STARRRS initiative. Another new initiative that stemmed from the summit and that also
is underway — Collaboratory on Research Definitions for Cognitive Reserve and
Resilience — brings together investigators from around the globe
to develop a consensus on uniform definitions for terms such as
“cognitive reserve,” “brain maintenance,” “resilience,” and “compensation” so that
the research community will have a common language and
understanding for reporting of results. Use of uniform definitions offers many
benefits, including the pooling of data across studies to allow for adequately
powered analyses and better interpretation of data. “It’s one thing to say,
‘life exposures might increase reserve,’”
says Stern, who serves as the primary
investigator for the collaboratory charged with the definitions task.
“It’s another thing to say, ‘we propose that the types of occupation people have
can allow them to cope better with amyloid pathology.’ We can measure amyloid,
we can measure cognition, and we can show how life exposure actually moderates
between the two. In other words, we can turn a concept into a very concrete
recipe for analysis.” In February 2020, NIA issued an additional funding
opportunity that stemmed from the Cognitive Aging Summit for support of
research to understand factors that promote sustained cognitive health in older
age: RFA-AG-21-015,


Although chronological age itself remains the strongest
predictor of age-related cognitive decline and many forms of dementia, including Alzheimer’s,

it has become clear there are protective factors against these outcomes that are poorly understood.

Awarded grants will support aggregation of sufficient numbers of these cognitive super agers to advance the field’s
understanding of factors that promote sustained cognitive health and those that are not of primary
importance. Working in part with funds contributed by MBRF in conjunction with FNIH, NIA invites
applications to identify, evaluate, and track individuals with superior cognitive performance for
their advanced age across multiple sites. The deadline for submission of applications is
October 1, 2020.

Further research on cognitive super agers could lead to strategies that everyone
can use — in younger years, in midlife, and in older age — to maintain thinking and memory skills.

Just as important, it could also provide insights into how dementias such as Alzheimer’s might
be prevented or reversed and provide critically important information for the identification of
targets for interventions. And by identifying the factors that affect brain health, this research
might one day be used to reduce disparities in brain-enriching opportunities so that everyone has a
chance to keep their brain at maximum power throughout life.