For the forgetful in menopause, brain works harder to keep up

During and after menopause, many women complain their memories are slipping. They're wrong--and right.
(Robert Durell/Los Angeles Times)
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Around the time of menopause, many women complain of mental slippage. But, as if to inflict some perverse trick upon them, cognitive scientists have found that they actually perform no more poorly than women who do not have such complaints. (Reassuring in a way: You’re not losing your memory, but you may be losing your mind.)

A new study finds that both the women who complain of memory problems and the cognitive scientists are right. These women haven’t fallen behind -- not yet at least-- because their brains are working harder to keep up.

The study, presented Sunday at the Society for Neuroscience’s yearly confab -- held this year in Washington, D.C. -- recruited 22 healthy women with an average age of 57, all post-menopausal. A battery of tests identified 12 as “cognitive complainers” -- meaning, they believed that in recent years, their memories had begun to slip. All the women were put in a brain scanner -- a functional Magnetic Resonance Imaging (fMRI) scanner -- that tracks activity in the brain in response to a task. The women then were given tasks that tested their working memory (sometimes called short-term memory) -- the ability to hold at least a few items in mind for less than a minute and to return to them, often after a distraction.


Compared with the 10 women who did not complain of mental slippage, the 12 complainers -- true to form -- showed no difference in their performance on short-term memory tasks. But their subjective experience of losing it was not baseless: To keep up, their brains showed far more exertion, on average, in parts of the brain that govern and support short-term memory. The dorsolateral prefrontal cortex and the anterior cingulate cortex of a “cognitive complainer,” on average, was working overtime to perform as well as her unaffected peers.

Odds are, said Julie Dumas, the University of Vermont neuroscientist presenting the study, that some of these cognitive complainers might go on to develop more serious intellectual deficits -- either mild cognitive impairment or dementia, including Alzheimer’s disease. In studies of older populations of cognitive complainers -- average age, 67-- 50% of people who reported a subjective experience of intellectual slippage went on to develop dementia versus 15% of those who didn’t have such complaints.

With mounting research showing that the processes of brain degradation begin years before symptoms of memory loss and disorientation become apparent, the researchers think they may have discerned the earliest signs of “cognitive compensation,” whereby people whose memory has begun to slow use clever strategies (including greater effort) to make up for the loss.

Perhaps, said Julie Dumas of the University of Vermont’s Clinical Neuroscience Research Unit, fMRI imaging during memory tasks could be used to detect such compensatory effort and help identify some of the earliest signs of dementia.

So is menopause even a factor here? Is the link between changing midlife hormones and brain fog real? That, says Julie Dumas, of University of Vermont’s Clinical Neuroscience Research Unit, remains uncertain. Past efforts to find a clear link between menopause’s plunging female hormone levels and changes in cognition haven’t yielded a clear link. (Although mood change s-- which can lead to changed intellectual performance -- are well linked to menopause’s hormonal changes.)

But hormone replacement therapy (HRT) -- controversial since the 2003 Women’s Health Initiative Study first linked it to higher rates of breast and ovarian cancer -- suggests an answer: Women who have taken HRT in the past were found to have brains with greater volumes of gray matter. And more gray matter is linked to better mental performance.


A second study presented at this week’s Neuroscience meeting looked at estrogen replacement not in the rear-view mirror, but in a clinical trial designed to detect changes in gray matter density in response to supplementary estrogen. It found that giving estrogen to post-menopausal women made their brain’s gray matter denser. The study, presented by Dr. Paul Newhouse of Vanderbilt University, divided 24 healthy postmenopausal women with an average age of 59 into two groups: the first got 1 milligram of estradiol (a synthesized version of estrogen) everyday for three months; the second got a daily dose of placebo.

At the outset and at the three-month mark, researchers used an MRI scanner that takes extremely detailed measurements of all the brain’s structures to detect any changes in the womens’ brains.

Compared with the women who took a placebo for three months, those who got estradiol had significantly greater gray matter density in three important areas -- the parietal temporal and prefrontal cortices -- on both sides of the brain. While those regions have a wide range of functions, they are key nodes in the networks that govern attention, episodic memory (memory for events and experiences) and working -- or short term memory.

Estrogen-induced changes in the brain “may be important in preserving cognitive function, especially in the early menopausal period,” said Dr. Newhouse, who acknowledged that estrogen treatment will probably remain controversial despite tantalizing efforts of its cognitive benefits.

At the same time, Newhouse said it’s not clear whether there exists an ideal window of time in a woman’s life when a short course of estrogen might help protect against memory problems or dementia without unduly raising risks of other illnesses.

Studies are increasingly finding that for menopausal women, estrogen replacement alone (as opposed to HRT that uses a mix of estrogen and progestin) does not increase breast cancer risk so long as it is taken for less than 10 years.


University of Vermont and Vanderbilt are working together to study women, menopause and cognitive function, and Dumas said the next step with her cognitive complainers will be to see if a course of estrogen helps them.