Robert Wilson in his now infamous Feminine Forever, published in 1966, included Bloss of memory as a menopausal symptom. Although his claim was casually proffered without substantiating evidence, memory complaints are indeed common during midlife.
In the Seattle Midlife Health Study, for example, 62% of 230 women responded Byes when asked whether they had noticed memory changes during the past few years.
Similarly, when we asked participants in the Melbourne Women’s Midlife Health Project whether during the preceding week they had particular trouble recalling recent events, 36% of 249 women replied affirmatively. Because midlife is a transitional period of hormonal change, one might easily ascribe memory symptoms to con- current endocrinologic changes. Wilson certainly would have.
Of these changes, most salient is the loss of estradiol, cyclically produced in women of reproductive age by the maturing ovarian follicle.
There are various forms of memory, implicating different brain loci and different neurophysiological processes. The type with perhaps the greatest clinical import is episodic memory.
This form of memory involves exposure to new information during a discrete event, or episode, and then conscious recollection of this information at a later time. The interval between exposure and recall can vary between minutes and days, or even years. In the 1950s, it was discovered that surgical resection of the hippocampus and nearby portions of the temporal lobes led to a profound, permanent inability to acquire new episodic memories.
In striking contrast, previously learned memories were largely spared. It is now appreciated that new memory formation of this type depends critically on integrity of the hippocampus and adjacent structures of the medial temporal lobes of the brain, although the memories themselves or, more precisely, the neural substrates on which these episodic memories depend are not themselves located within the medial temporal lobes. In the laboratory, effects of estradiol on hippocampal function would seem to enhance episodic memory.
Episodic memory deficits are especially characteristic of Alzheimer disease. People with this disorder usually recall remote events from childhood and early adulthood. Moreover, they retain new information for short intervals; for example, a woman with Alzheimer’s disease can often repeat back a name or telephone number immediately after presentation. Typically, however, she will not recall the same name or number a few minutes later. Ominously, older people with episodic memory impairment in the absence of dementia face greatly increased odds for developing overt Alzheimer disease within a several year span.
For this reason, the perception of poor memory can be alarming to the midlife woman and disquieting even for her physician. Fortunately, the concern is often misplaced. First, memory symptoms may be common, but dementia during middle age is rare.
Second, consistent findings in several midlife cohorts indicate that episodic memory is largely unaffected by the natural menopausal transition.
Third, during middle age, there is no link between circulating levels of estradiol and scores on objective tests of episodic memory.
Fourth, as reported in this issue by Weber and Mapstone, subjective forgetfulness during the menopausal transition is unassociated with objective scores on a standard test of episodic memory in this instance, 30-minute delayed recall on a word-list learning task.
Why, then, is midlife memory perceived as so problematic, particularly if memory is not in reality as bad as imagined?
Two considerations seem particularly germane: the relation between perceived memory and mood and the relation be- tween perceived memory and episodic memory. In older adults, it has long been appreciated that subjective memory complaints are closely linked to low mood.
The same is probably true at any age. In the Seattle Midlife Health Study, depressed mood was associated with the perceived frequency of memory problems, ratings of current memory, and memory change. Perceived memory function was also related to perceived health and stress.
A British survey of women from a general practice list similarly concluded that anxiety and depressive symptoms were the main predictors of self- reported memory complaints.
Weber and Mapstone also found that memory complaints in their middle-age volunteers were best predicted by depressive symptoms. One practical
consideration from these findings is that physicians and nurse practitioners should consider depression as an underlying factor in their middle-age patients with memory complaints.
Although sometimes overlooked, a complaint of forgetfulness or poor memory may reflect cognitive deficits other than episodic memory. There may, in fact, be no memory loss, if memory is taken to mean episodic memory, but other cognitive domains have been less thoroughly assessed during the natural menopausal transition and early postmenopause.
Most of the 24 women aged 40 to 57 years studied by Weber and Mapstone
reported some degree of memory loss. Women with poorer perceived memory function scored on average within the normal range on all cognitive tasks. How-
ever, these more symptomatic participants performed less well on average than women with better perceived memory function.
Differences were statistically significant on several neuropsychological measures. These were digit span and letter-number sequencing tasks from the Wechsler Memory Scale, phonemic (but not verbal) fluency, and immediate
recall on the first trial of the word-list learning task.
Given the small size of this convenience sample and the necessarily observational design, the clinical implications of these significance differences cannot yet be stated. In much larger cohorts, the menopausal transition was unassociated with changes on measures of digit span and phonemic fluency.
Furthermore, a well-designed, randomized, placebo-controlled trial conducted among women who had undergone natural menopause, were still in the early postmenopause, and had cognitive complaints found no effect of estrogen-containing hormone therapy on word-list learning, phonemic fluency, or digit span.
These intriguing new findings, however, in conjunction with prior research do raise the important possibility that perceived memory impairment is sometimes tied to objective impairment on cognitive tasks other than episodic memory.
If this association is confirmed, it will remain to be determined whether this association is dependent on or independent of menopause status or whether it is in some way modified by the midlife hormonal milieu.
Financial disclosure/conflicts of interest: None reported.
Victor W. Henderson, MD, MS
Departments of Health Research & Policy and of
Neurology & Neurological Sciences
Stanford University
Stanford, CA
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Menopause, Vol. 16, No. 4, 2009
* 2009 The North American Menopause Society EDITORIAL