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Harvard
University Gazette
Fountain
of Youth Bubbles in Brains of the Oldest Old
March 5, 1998
By Cassie Ferguson
Death
and taxes are still certain, but according to a Medical School
study, the mental infirmities of old age are not.
Neuropsychological
examinations and autopsies of people who live past 100 show
that they can live to the end with sound minds, report the
researchers in the upcoming issue of International Psychogeriatrics.
"It
has been common thinking that dementia's inevitable with old
age. That isn't so. We're studying centenarians whose thinking
is perfectly clear. And their brain autopsies confirm what
we see," said Margery Silver, associate director of the New
England Centenarian Study and clinical instructor in psychology
at the Medical School.
"I
marvel at these brains. Some could pass for individuals 20
or 30 years younger," said Kathy Newell, a clinical fellow
in neuropathology at Massachusetts General Hospital. "Many
were basically healthy looking brains with a nice size, normal
weight, and little or no evidence of atrophy."
Silver
and her colleagues at the Centenarian Study tested the cognitive
function of 69 centenarians, finding that although the hyper-aged
frequently have some degree of dementia, 20 percent have survived
the years in perfect mental health.
Guessing
that the brains of centenarians might mirror the results of
the neuropsychological tests, they asked pathologists from
Massachusetts General Hospital to take a post-mortem look
at the condition of study subjects who had willed their brains
to science.
The
autopsies revealed that half had resisted the onslaught of
tiny strokes as well as fatty plaques and proteins thought
to choke blood vessels and strangle brain cells as brains
age, possibly causing Alzheimer's disease and dementia. Of
the six examinations reported in the paper, none was diagnosed
with Alzheimer's disease.
Since
the brains of the centenarians can be unexpectedly free from
the physical proof of old age, Silver suggested that dementia
sometimes attributed to people who have reached at least 100
might be misattributed and even reversible.
"There
are lots of treatable causes for dementia. Doctors may be
missing something that's curable. The dementia might be caused
by something like depression, medication for heart disease,
or B-12 deficiency," she said.
This
is good news for the projected 500,000 to 4 million people,
who'll be blowing out at least 100 birthday candles in the
middle of the next century. (Continued)
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The Centenarian Prevalence
Study
The New England Centenarian Study is an attempt to find and
recruit all the centenarians (and their families) living in
eight towns surrounding and including Boston, Massachusetts.
As such, it is the only population-based study of centenarians
in North America. By choosing a circumscribed population and
enrolling approximately all the centenarians in that area,
we do our best to prevent selection bias in the study and
therefore obtain a valid and representative picture of centenarians
living in the northeastern United States.
The population size of our study area is 460,829 people and
it is made up of the following towns: Belmont, Cambridge,
Somerville, Dedham, Quincy, Framingham, Waltham, and Lexington.
We chose these particular towns because of their local proximity
to the Harvard Division on Aging and our preliminary work
indicating the high sensitivity of their censuses in listing
centenarians. These censuses are nearly 100 percent sensitive
(and detect all the centenarians in the population) and about
30 percent specific (30 percent of the centenarians detected
are alive). We have verified the ages of 46 centenarians living
in this area. Therefore, the prevalence rate, as of December
31, 1996, was about one centenarian per 10,000 people. This
translates into about 650 centenarians for the state of Massachusetts.
This demographic study of the ability to verify ages and to
determine prevalence appears in the March 1999 issue of Age
and Ageing.
Estimates for the number of centenarians in the United States
hover around 50,000 though if one applies a rate of 1 per
10,000 to the country as a whole, the prevalence would be
closer to 30,000. Because centenarians are the fastest growing
segment of our population, there will be many more of them
in the near future. By the middle of the next century, with
the continuing aging of the baby boomers (73 million strong),
estimates for the number of centenarians range from 500,000
to five million!
Neuropsychological and neuropathological assessment
We are assessing the cognitive function of our subjects because
we believe that Alzheimer's disease is either markedly delayed
or even absent in some subjects. This is based upon the premise
that people have to be very healthy the vast majority of their
lives in order to successfully reach age 100. Because Alzheimer's
is a lethal disease over the course of 8-10 years, if one
is going to develop this disease and still make it to 100,
one would have to develop it no earlier than in their nineties.
Approximately 30 percent of our subjects consent to donate
their brains for detailed study after they have passed away.
In this way we can correlate how the person was doing cognitively
while alive, with what their brain looks like. Our collaborators
in this effort include the Alzheimers Disease Research Center
at Massachusetts General Hospital: Marilyn Albert Ph.D., Kathy
Newell M.D., Bradley Hyman M.D., Ph.D., John Growdon M.D.,
and T.Hedley-Whyte M.D. We report the results of this neuropsychological-neuropathological
correlation in the January 1999 issue of the Journal
of the International Psychogeriatrics. Our work in this
area was also noted in the January 24-31, 1998 issue of The
Economist, and the March 5, 1998 issue of the Harvard
Gazette.
Many people believe dementia is an inevitable consequence
of aging. If this were the case one might expect all centenarians
to have dementia. We have found three centenarians who were
completely cognitively intact at the time of death and their
brains appeared entirely normal without the typical neuropathological
markers of dementia, especially those of Alzheimer's disease.
Thus, at least some people can live to extreme old age without
dementia.
We are in the process of proving that centenarians either
escape or at least markedly delay the onset of Alzheimer's
disease. The next important question is how are they able
to do this? Therefore, we are now conducting a molecular genetics-based
search for the genes that impart protection and/or the genes
that are absent which would cause or increase the susceptibility
for the disease. We are already taking this next step in another
aspect of our work: The Centenarian
Sibling Pair Study.
Margery H. Silver Ed.D., the Associate Director of the New
England Centenarian Study, heads the neuropsychological assessment
of our subjects.
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