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Age-Linked Memory Loss May Be Worse for Men, Study Finds
And, early plaque build-up in brain may not play as strong a role in recall issues as suspected
By Amy Norton
MONDAY, March 16, 2015 (HealthDay News) -- Can't remember that work colleague's name? Misplaced your keys again? Don't fret: a new study finds that nearly everyone will suffer more memory lapses as they age, with men being more vulnerable to failing memory than women.
The study also reported that people's memory skills and brain volume typically decline with age -- and, surprisingly, it seems to have little to do with the buildup of brain "plaques" that mark Alzheimer's disease, the study suggests.
The researchers said their findings challenge a prevailing view on the aging brain.
Experts have speculated that when older adults start having memory lapses, it may be a sign of early Alzheimer's disease -- and likely related to abnormal clumps of a protein called beta-amyloid that accumulate in the brain.
"But our findings suggest that memory actually declines in almost everybody, and well before there is any amyloid deposition in the brain," said Dr. Clifford Jack, a researcher at the Mayo Clinic in Rochester, Minn., who led the study.
Beta-amyloid deposits -- commonly called plaques -- are still a hallmark of Alzheimer's disease, Jack said. But the new findings suggest that they do not "initiate" the disease process, and instead enter the picture later.
"There seems to be a profound effect of aging, itself, on memory -- independent of amyloid," Jack said. "We think that [amyloid] pathology tends to arise late in life, to accelerate a pre-existing decline in memory."
According to Jack, that offers some good news.
"The memory decline that people often experience as they get older is usually not an indicator of underlying Alzheimer's pathology," he said. "So it in no way means you're inevitably going to become demented."
Other researchers called the findings "very important."
"What this shows very clearly is that memory and brain volume are declining years before any amyloid is present," said Dr. Charles DeCarli, a professor of neurology at the University of California, Davis.
The bottom line is, age-related mental decline "is not as simple as we'd like it to be," said DeCarli, who wrote an editorial published with the study.
The results are based on over 1,200 adults from one county in Minnesota. All were between the ages 30 and 95, and had no symptoms of dementia. They all took standard memory tests and underwent two types of brain scan: an MRI to measure the volume of the hippocampus, a brain structure involved in memory; and a PET scan to look for amyloid buildup.
According to Jack, it's only in the past few years that researchers have had technology capable of imaging amyloid.
And what his team found was surprising: Overall, both memory and brain volume gradually declined from age 30 to the mid-60s. But few people showed any amyloid buildup during that time. It wasn't until around age 70 that there was a substantial increase in the number of people who were "amyloid positive" on PET scans.
That was particularly true for people who carried the APOE4 gene variant -- which is linked to a higher-than-average risk of Alzheimer's. People with the APOE4 gene variant began to show amyloid at a younger age, and showed a steeper increase in amyloid buildup after age 70.
However, the study also found that APOE4 carriers showed no greater decline in memory or brain volume.
Jack said the memory finding was "a little surprising." But, he noted, all of the study participants were dementia-free; APOE4 carriers are at increased risk of Alzheimer's -- but in the absence of that, they might not have worse memories than people who don't carry the gene.
Instead, men consistently had worse memories than women, and (proportionately) a smaller hippocampus, at all ages, the findings showed.
Other studies have found that women do better on memory tests, but Jack said it's still a striking finding. "Basically," he said, "this is saying that being a man has a much bigger effect on memory than being an APOE4 carrier does."
Jack suspects that men's higher rate of cardiovascular risk factors -- which have been increasingly linked to the development of memory problems -- might be one reason why men have poorer recall than women. Or, it may be some protective effect from the hormone estrogen in women, he suggested.
Before men panic, DeCarli noted that full-blown dementia is no more common among men than women -- though that may be because women generally live longer.
So if amyloid deposits are not causing the gradual memory decline so many people see, what is?
Jack pointed to one likely culprit: Heart disease, stroke and the risk factors for those conditions -- such as high blood pressure and diabetes. All can impair blood flow to the brain, and may cause brain tissue to shrink.
DeCarli agreed, but said other factors have to be at work, too.
Mary Sano, an Alzheimer's researcher at Mount Sinai, in New York City, said the findings are "exciting."
A lot of research aimed at preventing Alzheimer's has focused on amyloid buildup, Sano noted. But this study, she said, suggests other avenues -- including "interventions that focus on brain volume" -- should be explored, too.
And how do you change brain volume? Exercise is one possibility. "Research has shown that physical activity may slow the brain volume loss that comes with aging," Sano said.
To DeCarli, the findings highlight how much scientists have left to learn about the aging brain -- and aging, in general.
"Why does your skin get dry as you grow older?" he said. "Why does your hair go gray? We really don't know much about aging."
Results of the study were published online March 16 in JAMA Neurology.
The U.S. National Institute on Aging has more on memory loss.
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