Doctors used to think that hardening of the arteries was responsible for declining memory. Then studies suggested that an estrogen shortfall might be one of the culprits. This seemed to explain why so many women forgot names or dates, misplaced their keys, and complained of fuzzy thinking starting at midlife. For a while clinicians relied on hormone therapy to alleviate these symptoms and prevent more serious problems later on.
Now, the Women's Health Initiative Memory Study (WHIMS) suggests that, far from having a beneficial effect on memory, hormone therapy might even speed the onset of dementia in post-menopausal women who begin taking hormones at a later stage.
Will the results be the same for younger women? Does the duration of treatment matter? The jury is still out on these and other important questions.
Investigators have also suggested that memory problems during menopause may not arise from structural changes in the brain, but from increasing stress. In addition, we need to know more about the links between memory loss, depression, and menopausal sleeplessness.
To explore the subject of menopause and memory, our managing editor, Valerie Andrews, talked with researcher Victor Henderson, director for Geriatrics and Extended Care at the Central Arkansas Veterans Healthcare System, professor of geriatrics and neurology at the University of Arkansas for Medical Sciences and an authority on age-associated memory loss, Alzheimer's disease, and related cognitive disorders.
Dr. Henderson currently directs the Rural Aging & Memory Study in Bradley County, Arkansas and is an investigator with the Melbourne Women's Midlife Health Project. He also serves on the External Advisory Board of the Women's Health Initiative Memory Study and is the author of Hormone Therapy and the Brain (NY: Parthenon Publishing, 2000.)
What do we know about the relationship between memory and aging?
Several large observational studies show that women who have used hormone therapy at some point after menopause seem to have a lower risk of developing Alzheimer's disease. But more recently, the Women's Health Initiative Memory Study (WHIMS) http://www.wfubmc.edu/whims/ found no appreciable advantage for estrogen-plus-progestin hormone therapy. In fact, in this trial women assigned to hormone therapy showed a higher rate of dementia when compared to placebo. The results for women taking estrogen alone have not yet been published.
The WHIMS trial, like almost all research trials, was far from perfect, but it gave us new data on what happens during an important period of a woman's life. The message is that women between 65 and 79 years of age who initiate combination hormone therapy at this time of life have an increased risk of dementia.
In this study, Alzheimer's disease wasn't considered separately from other causes of dementia, and the numbers were too small to tell us for certain if WHIMS findings specifically indicate an increased rate of Alzheimer's disease, but in my view it very likely does.
One difficulty is that we don't know if WHIMS findings should be applied to women under the age of 65. The WHIMS study also doesn't tell us if estrogen would harm or benefit memory if hormone replacement is started at a younger age.
Most women who use hormone therapy start therapy around the time of menopause. Moreover, observational studies showing a protective effect of hormone therapy have generally involved women who initiated hormone therapy earlier than women in the WHIMS trial.
For the time being, though, I would not presume a memory benefit for younger women. We need to wait for more data to come in.
When will we know more about the relationship between hormone therapy and menopausal memory in general?
A new study, called the KEEPS study (Kronos Early Estrogen Prevention Study http://www.kronosinstitute.org/keeps.html) will look at the effects of different forms of hormone therapy in younger post-menopausal women, but this trial is just now beginning, and investigators won't have results for a number of years.
During menopause, women often complain of "brain fog" or memory loss. How common is this?
Many women do report a decline in memory as they reach middle age. However, this issue has not yet been carefully studied. To date, researchers have been unable to prove by formal memory testing that memory deterioration actually occurs at this time of life.
Last year, we reported on memory in over 300 middle-aged women in Melbourne, Australia (VW Henderson et al, Neurology 2003;60(8):1369-1371). Our memory test required women to learn a list of 10 words and then recall the words after a short delay. Memory scores were unrelated to menopausal status or to levels of estrogen measured in a blood sample.
Though it did not focus on memory, the multi-center Study of Women Across the Nation (SWAN) http://www.edc.gsph.pitt.edu/swan/public/ found that mental skills did not decline after menopause when compared with pre-menopausal scores.
What about the relationship between memory and stress?
At midlife women may experience higher levels of stress as they deal with growing children, ailing parents, job responsibilities, and hormonal changes that affect sleep. Sleep deprivation certainly can impair memory and other mental abilities, as can stress.
The brain is an amazing organ. People have a surprising capacity to learn and retain new information. When we are confronted with a lot of new information all at once, we need to focus on what's important, screen out what's irrelevant, and organize important material in a way that it can be efficiently committed to memory.
But stress reduces our ability to juggle lots of tasks simultaneously. A little stress actually helps people retain information better, but a lot of stress makes learning and memory worse. Once stress levels become too high, things start to deteriorate. Some of the research findings on long-term stress are more controversial. Some investigators believe that chronic, severe stress actually damages nerve cells in the specific part of the brain involved in learning and memory.
What are the most common memory complaints for women in midlife?
Let me give you some examples. A woman might walk into a room and then forget the task she came in to accomplish. Or she might forget names of acquaintances, movie titles, and so on. In middle age and even more so in old age, people will say, "The name is on the tip of my tongue, but I just can't come up with it." Or, "I was talking on the phone to a friend about a book I had just finished reading, and, for the life of me, I couldn't come up with the title. It came to me a few minutes after I hung up."
There is some question whether these word-finding difficulties are related to memory problems, per se, to an information-processing impairment, or to some other cognitive problem.
Are word-finding difficulties anything to be concerned about?
I think it's important to reassure women that difficulty coming up with names is generally not believed to be an early sign of Alzheimer's or other forms of dementia. I would be concerned if a person were consistently forgetting appointments or prior conversations or had difficulty recalling what happened yesterday. These symptoms usually affect older individuals and are the kind that may warrant medical assessment.
Is there any research linking hormone levels to the kind of word-finding difficulties that begin around the menopausal transition?
Some studies in younger women suggest that articulation — which isn't exactly the same thing as coming up with word names — is better during the high-estrogen part of the menstrual cycle as compared to menstruation, when estrogen levels are low. There is also evidence that estrogen might enhance learning and recall of information that is verbally encoded — information from a word list, for example, or details from a short story.
Dr. Barbara Sherwin at McGill University published a randomized, placebo-controlled study of women undergoing surgical menopause — removal of the uterus and ovaries. She reported that for these women estrogen can preserve or enhance verbal memory. However, it had no apparent effect on memory that doesn't require verbal encoding.
We have studies underway that will examine effects of estrogen on naming skills for women undergoing natural menopause.
I should also add here that researchers have looked at naming and memory in older post-menopausal women, and there is no strong evidence that older women who initiate hormone therapy will show memory improvement.
What about anecdotal reports that estrogen replacement helps women "think better?"
Researchers have certainly heard women on estrogen patches or oral hormone therapy say they can think more clearly as a result of treatment. Still, we have yet to understand exactly what's going on.
One possibility is the improvement some women perceive is related to mood. In the Melbourne Women's Midlife Health Project we found a relation between low mood and poor memory, but I suspect there's more to these women's experiences than mood alone.
Can you tell us more about the impact of depression on the brain?
Depression is definitely linked to memory deficits. This association has been shown in any number of studies, and it is true for both women and men.
Menopause per se does not appear to cause depression, yet women with a prior history of depression are more likely to experience new depressive symptoms during the menopausal transition. Research conducted by Professor Lorraine Dennerstein in Melbourne, Australia, indicates that other factors can contribute to depressed mood during this time of life. These include daily hassles, poor physical health, a history of premenstrual problems, and negative attitude toward aging.
Might some women respond better than others to hormone therapy because they are more sensitive to its effect upon the hippocampus, that portion of the brain that governs not just memory, but emotion?
That's a good question, but I'm not sure I or any one else can provide a good answer. Estrogen does exert a number of effects on the hippocampus that would be expected to benefit memory. Some women may well experience hormone therapy differently, and it is possible that estrogen's effects on the brain could vary from person to person.
Do women have more difficulty with memory loss than men?
Middle-aged and elderly men also have trouble with recalling names or learning new information, and it is not at all clear that the magnitude of the problem is any different for women than for men. At this point we don't even know for sure whether problems with recall occur in direct relation to menopause and hormonal shifts or as a general aging effect.
Since hormone therapy requires further study, what else can women do to safeguard memory and cognitive function?
Work on reducing stress levels. Stress is especially common during midlife. Some hassles are unavoidable, but it is reasonable to refrain from taking on too many tasks at once. Try to stay clear of unduly stressful situations. Don't volunteer for an extra project at work during the week when your mother-in-law is visiting and your teenager needs extra help with algebra assignments. Take time for yourself. Set aside time for relaxation.
Vasomotor symptoms like hot flushes may disrupt sleep. If this is the case, make sure you get more sleep time to make up for this. Some women also develop sleep apnea — which is trouble breathing while asleep — after menopause, and in these cases, evaluation by a sleep specialist can be helpful.
Seek help if your energy level seems near zero, or you feel down in the dumps for a period of time. Good nutrition is important, though I believe too many people over-emphasize costly nutritional supplements at the expense of a balanced diet. Finally, physical exercise has multiple benefits, and there is some evidence that it can benefit cognition. [We will explore the role of exercise in mood, memory and mental functioning in a forthcoming article —Ed.]
For information on menopause and memory: North American Menopause Society, http://www.menopause.org/
For information on dementia and Alzheimer's disease: Alzheimer's Association, http://www.alz.org/
This article is for educational purposes only and is not intended as a substitute for medical advice. Please consult with a clinician to review any current symptoms and address your medical concerns.
