13 August, 2012:
Memory complaints are relatively common during midlife. Depending on how the question is asked, more than half of midlife women will endorse problems with memory, and many will indicate that poor memory carries over to their daily function [1-4]. A major concern of patients and their physicians is that forgetfulness, poor concentration, or simply just fuzzy thinking might portend more serious cognitive impairment in the years to come. Among midlife women, a related question is whether their memory symptoms are caused by hormonal fluctuations or hormonal loss associated with the menopausal transition and postmenopause.
In the July issue of Menopause, Weber and her colleagues  report findings on 75 midlife women. They examined the relation between memory complaints and cognitive performance on a comprehensive battery of neuropsychological tests, and the relation with serum estradiol levels. These women, who were aged 40–60 years, were asked to rate their memory with the 64-item Memory Function Questionnaire (MFQ). Their answers were analyzed according to total score as well as factors related to Frequency of Forgetting, Seriousness of Forgetting, Retrospective Functioning (current memory relative to past memory), and Mnemonics Usage. Self-rated mood was assessed with the Beck Depression Inventory.
About two-thirds of women in this analysis reported at least some degree of memory loss, and a quarter endorsed symptoms of mild to moderate depression. The relation between the two was highly significant (r = -0.53 for the total MFQ score and the Beck Depression Inventory, p < 0.001), as was the association between MFQ and a measure of anxiety (r = -0.33, p = 0.003). There was no significant relation, however, between the MFQ or MFQ factors and objective measures of memory. For example, the correlation (r) between total MFQ and delayed recall on a list-learning task was only 0.05 (p = 0.7).
A very interesting finding emerged when other aspects of cognition were examined. One of the neuropsychological tests, Letter-Number sequencing, required the mental manipulation of letters and numbers read aloud to study participants, who then had to rearrange these in numerical and alphabetical order. This complex attentional task implicates brain processes involved in the temporary maintenance and manipulation of information. The association with the total MFQ was significant (r = 0.28, p = 0.015), as were associations with Frequency and Seriousness of Forgetting. Another attentional task, which depended heavily on vigilance, correlated with Frequency of Forgetting, and Weber and colleagues conclude that 'memory complaints in the menopausal transition may reflect true difficulties with attentionally mediated cognitive processes' (p. 735). The estradiol level was not significantly correlated with the MFQ or with objective measures of memory or attention. Study limitations include the cross-sectional nature of the analyses and the absence of correction for multiple comparisons.
Findings of Weber and colleagues  complement those recently reported by Australian investigators . Among midlife women in the sample of Schaafsma and colleagues , memory complaints were associated with poorer attentional skills, as assessed by reaction time tasks. The authors also found cross-sectional associations with poorer memory. Together, the two studies indicate that subjective memory impairment at midlife may reflect objective cognitive impairment, which is more consistently related to attention than to other aspects of cognitive function.
In the analyses of Weber and colleagues, memory symptoms were more strongly linked to low mood than to any other variable. This association is consistent with that reported in older adults and is thus perhaps not surprising. Moreover, depression can impair cognitive performance, and it can lower the perception of one's cognitive performance.
The absence of a strong link to objective memory loss is reassuring. Although a clear relation between abnormal memory in midlife and dementia risk has not been established, in older adults memory decline beyond that expected on the basis of usual aging is a significant predictor [5,6]. Modest cognitive declines in domains apart from memory appear to carry less significance.
In the Seattle Midlife Women's Health Study, forgetfulness or difficulty concentrating was closely related to hot flushes, anxiety, depressed mood, perceived stress, perceived health, or sleep disruptions . Physicians confronted with the issue of subjective memory loss during the menopausal transition and early postmenopause should keep in mind that there may indeed be problems with attentional abilities. They should also consider that dementia during midlife is rare; subjective memory loss is common (and is confined neither to midlife nor to women). There is no evidence of objective memory loss across the natural menopause transition (surgical menopause is less well studied), and estradiol levels during midlife are not associated with objective memory performance [7,8]. Depression or anxiety, if identified, is amenable to treatment, as are hot flushes, midlife stressors, poor sleep hygiene and other sleep disorders. For many women, memory symptoms during midlife represent an opportunity for her and her physician to consider interventions that may improve her quality of life.
Victor W. Henderson
Stanford University, Stanford, California, USA
1. Mitchell ES, Woods NF. Cognitive symptoms during the menopausal transition and early postmenopause. Climacteric 2011;14:252-61. http://www.ncbi.nlm.nih.gov/pubmed/21526517
2. Simon JA, Reape KZ. Understanding the menopausal experience of professional women. Menopause 2009;16:73-6. http://www.ncbi.nlm.nih.gov/pubmed/18779760
3. Schaafsma M, Homewood J, Taylor A. Subjective cognitive complaints at menopause associated with declines in performance of verbal memory and attentional processes. Climacteric 2010;13:84-98. http://www.ncbi.nlm.nih.gov/pubmed/19722118
4. Weber MT, Mapstone M, Staskiewicz J, Maki PM. Reconciling subjective memory complaints with objective memory performance in the menopausal transition. Menopause 2012;19:735-41. http://www.ncbi.nlm.nih.gov/pubmed/22415562
5. Elias MF, Beiser A, Wolf PA, Au R, White RF, D'Agostino RB. The preclinical phase of Alzheimer's disease: a 22-year prospective study of the Framingham cohort. Arch Neurol 2000;57:808-13. http://www.ncbi.nlm.nih.gov/pubmed/10867777
6. Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 2012. Epub ahead of print. http://www.ncbi.nlm.nih.gov/pubmed/22784036
7. Henderson VW. Menopause, cognitive ageing and dementia: practice implications. Menopause Int 2009;15:41-4. http://www.ncbi.nlm.nih.gov/pubmed/19237622
8. Henderson VW. Gonadal hormones and cognitive aging: a midlife perspective. Women's Health (Lond Engl) 2011;7:81-93. http://www.ncbi.nlm.nih.gov/pubmed/21175393
Content updated 13 August 2012