- Email: [email protected]
Verbal memory and menopause
G Model
ARTICLE IN PRESS
MAT-6458; No. of Pages 3
Maturitas xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review article
Verbal memory and menopause Pauline M. Maki University of Illinois at Chicago, College of Medicine, Neuropsychiatric Institute (MC913), 912 South Wood Street, Chicago, Illinois 60612, USA
a r t i c l e
i n f o
Article history: Received 23 July 2015 Received in revised form 24 July 2015 Accepted 26 July 2015 Available online xxx Keywords: Menopause Memory Hormone therapy Hysterectomy Vasomotor symptoms Hot flush
a b s t r a c t Midlife women frequently report memory problems during the menopausal transition. Recent studies validate those complaints by showing significant correlations between memory complaints and performance on validated memory tasks. Longitudinal studies demonstrate modest declines in verbal memory during the menopausal transition and a likely rebound during the postmenopausal stage. Clinical studies that examine changes in memory following hormonal withdrawal and add-back hormone therapy (HT) demonstrate that estradiol plays a critical role in memory. Although memory changes are frequently attributed to menopausal symptoms, studies show that the memory problems occur during the transition even after controlling for menopausal symptoms. It is well established that self-reported vasomotor symptoms (VMS) are unrelated to objective memory performance. However, emerging evidence suggests that objectively measured VMS significantly correlate with memory performance, brain activity during rest, and white matter hyperintensities. This evidence raises important questions about whether VMS and VMS treatments might affect memory during the menopausal transition. Unfortunately, there are no clinical trials to inform our understanding of how HT affects both memory and objectively measured VMS in women in whom HT is indicated for treatment of moderate to severe VMS. In clinical practice, it is helpful to normalize memory complaints, to note that evidence suggests that memory problems are temporary, and to counsel women with significant VMS that memory might improve with treatment. © 2015 Published by Elsevier Ireland Ltd.
Contents 1. 2. 3. 4. 5. 6.
Practice points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Research agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Contributor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Verbal memory refers to memory for words, stories, and other verbal material. Since as early as 1894, a female advantage in verbal memory and other verbal tasks has been recognized and validated in empirical studies [1]. Clinical and basic science studies demonstrate sex differences in the structure and function of the hippocampus and temporal lobe that likely contribute to the female advantage [1]. Basic science studies contribute direct evidence that both activational and organizational effects of estradiol on these brain areas contribute to memory performance [1]. Evi-
Abbreviations: VMS, vasomotor symptoms; HT, hormone therapy; CEE, conjugated equine estrogen; MPA, medroxyprogesterone acetate. E-mail address: [email protected]
dence of activational effects in humans is found in studies showing declines in verbal memory following oophorectomy and treatment with gonadotropin-releasing hormone analogues (GNRHa) and improvement after supplementation with hormone therapy (HT) [2,3]. Organizational effects are supported by evidence of a female advantage in verbal memory during reproductive stages where there are only modest sex differences in circulating estradiol levels; girls outperform boys before the age of sexual maturity, and women outperform men after the onset of natural menopause and after oophorectomy [1]. If estrogen plays a role in establishing and maintaining the female advantage in verbal memory, then it stands to reason that subjective memory complaints and objective memory performance would decline during the menopausal transition. Complaints of for-
http://dx.doi.org/10.1016/j.maturitas.2015.07.023 0378-5122/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: http://dx.doi.org/10.1016/j.maturitas.2015.07.023
P.M.
Maki,
Verbal
memory
and
menopause,
Maturitas
(2015),
G Model MAT-6458; No. of Pages 3
ARTICLE IN PRESS P.M. Maki / Maturitas xxx (2015) xxx–xxx
2
getfulness are common during the menopausal transition in clinical samples and in samples representative of the general population [2]. Subjective memory complaints are associated not only with menopausal stage but also with advancing age, low education, lack of full-time employment, low physical activity, hot flushes, and concentration difficulties. Among samples of midlife women, there is considerable interindividual variation in subjective complaints and objective memory outcomes, but subjective complaints nevertheless correlate significantly with memory performance [3]. Generally then, although memory complaints and memory difficulties are not universal, women who report memory problems do perform lower on memory tests. Is there any evidence that menopause stage influences memory performance? Until recently, studies suggested no such relationship, but that conclusion was based on cross-sectional studies and prospective studies that did not include premenopausal estimates of memory. Relatively recent and large longitudinal studies provide new evidence that memory does decline during the menopausal transition but appears to rebound during the postmenopausal stage [4,5]. It is unclear why memory declines during the menopausal transition and then appears to rebound. A key role for estradiol in these changes is suggested by studies showing memory declines following acute declines in estradiol with a return to baseline memory function following add-back HT [6]. A common assumption is that memory problems are due to menopausal symptoms, and indeed menopausal symptoms are related to cognitive performance [4,5]. However, declines in memory during the menopausal transition persist after controlling self-reported VMS, sleep, depression and anxiety [6,7]. Similarly, although memory declines with advancing age, age cannot explain the declines occurring during the transition because they persist after controlling for age and memory appears to rebound during the postmenopausal stage despite advancing age. Although clinical studies reveal an association between cognitive complaints and self-reported VMS as measured by questionnaires or diaries [7], performance on cognitive tests is unrelated to those measures of VMS [8]. Emerging evidence, however, suggests that objective VMS might be more sensitive to cognitive and brain outcomes. While self-reported VMS are the appropriate patient-reported outcome for clinical trials of VMS treatments, compelling evidence in support of the validity of objective VMS comes from studies showing a strong placebo effect for selfreported VMS but not objective VMS as measured by ambulatory skin conductance monitors [9,10]. In one study, verbal memory correlated significantly with the number of objective VMS, but not to the number of reported VMS [11]. Similarly, recent studies showed that objective VMS, and not subjective VMS, were related to white matter abnormalities on structural brain scans and to alterations in brain function during rest [12,13]. These initial studies suggest that VMS might represent a female-specific risk factor for memory declines during the menopausal transition. To date, there are no longitudinal studies of the relationship between objectively measured VMS and memory across the menopausal transition. Such studies are needed to directly test the hypothesis that VMS contribute to memory declines during the menopausal transition and that memory rebound as VMS improve during the postmenopausal period. More broadly, this line of research raises important questions about which women might be particularly vulnerable to memory problems as they age reproductively. This question is of considerable clinical significance given new evidence from SWAN that frequent VMS last on average of 7.4 years[14]. Clinically, this issue is particularly important for minorities, as frequent VMS last an average of 10.1 in black women and 8.9 years in Hispanics [14]. The exact mechanism underlying the relationship between VMS and memory is uncertain, though cortisol is known to rise after a hot flush [15], and cortisol contributes to memPlease cite this article in press as: http://dx.doi.org/10.1016/j.maturitas.2015.07.023
P.M.
Maki,
ory impairments [16]. Further study of the relationship between objective VMS and memory is warranted. How should clinicians address the concerns of midlife women about memory problems? First, clinicians should normalize those complaints. About 40% of women in the menopausal transition complain of forgetfulness [2]. Qualitatively, women complain that they cannot remember people’s names as easily as they could in the past, and they find that when they are trying to remember something like the name of a film it is on “the tip of their tongue” but they cannot successfully retrieve the information. Many women, particularly those with a family history of Alzheimer’s disease, fear that these memory difficulties are a sign of early dementia. In this case, it can be helpful to inform women that only 5-10% of all Alzheimer’s cases have an onset before the age of 65. However, if she experiences a decline in daily function, such as getting lost in familiar surroundings and repeating herself routinely in conversations, refer her to a neurologist for further assessment. Treating depressive symptoms might also help to improve cognition. The risk for subclinical depressive symptoms as well as major depressive disorder is elevated during the menopausal transition [17] and clinical depression is associated with memory problems [18]. It is also important to encourage patients to practice good sleep habits by refraining from using computers and mobile phones and avoiding caffeine and excess alcohol before bedtime. HT should not be used for the sole purpose of improving memory. However, women receiving HT for the treatment of VMS might experience some improvements in memory, either directly due to effects of estrogen on memory systems or indirectly due to improvement in VMS and other menopausal symptoms. Lastly, sedentary women should be encouraged to engage in cardiovascular exercise to help memory problems [19]. 1. Practice points • Do not prescribe HT for the sole purpose of improving cognition. • Advise midlife women that memory complaints are common during the menopausal transition, and memory problems appear to return to baseline during the postmenopausal period. • Advise women that dementia is rare in midlife women, and refer to a neurologist only if memory problems significantly disrupt daily function. • Advise women to practice sleep hygiene and engage in cardiovascular exercise to improve memory. 2. Research agenda • To understand why memory changes during the menopausal transition, incorporate subjective and objective measures of VMS and other menopausal symptoms into prospective studies. • Conduct clinical trials of HT on memory outcomes in women with moderate-to-severe VMS. 3. Contributor Pauline Maki is the sole author. 4. Conflict of interest Dr. Pauline Maki consults for Abbott, Noven and Pfizer. 5. Funding The author has received no funding for this article.
Verbal
memory
and
menopause,
Maturitas
(2015),
G Model MAT-6458; No. of Pages 3
ARTICLE IN PRESS P.M. Maki / Maturitas xxx (2015) xxx–xxx
6. Provenance and peer review Commissioned; externally peer reviewed. References [1] J.M. Andreano, L. Cahill, Sex influences on the neurobiology of learning and memory, Learn. Mem. 16 (2009) 248–266. [2] E.B. Gold, B. Sternfeld, J.L. Kelsey, C. Brown, C. Mouton, N. Reame, et al., Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age, Am. J. Epidemiol. 152 (2000) 463–473. [3] L.L. Drogos, L.H. Rubin, S.E. Geller, S. Banuvar, L.P. Shulman, P.M. Maki, Objective cognitive performance is related to subjective memory complaints in midlife women with moderate to severe vasomotor symptoms, Menopause 20 (2013) 1236–1242. [4] C.N. Epperson, M.D. Sammel, E.W. Freeman, Menopause effects on verbal memory: findings from a longitudinal community cohort, J. Clin. Endocrinol. Metab. 98 (2013) 3829–3838. [5] G.A. Greendale, M.H. Huang, R.G. Wight, T. Seeman, C. Luetters, N.E. Avis, et al., Effects of the menopause transition and hormone use on cognitive performance in midlife women, Neurology 72 (2009) 1850–1857. [6] B.B. Sherwin, Estrogen and memory in women: how can we reconcile the findings? Horm. Behav. 47 (2005) 371–375. [7] N.F. Woods, K. Smith-Dijulio, D.B. Percival, E.Y. Tao, H.J. Taylor, E.S. Mitchell, Symptoms during the menopausal transition and early postmenopause and their relation to endocrine levels over time: observations from the Seattle Midlife Women’s Health Study, J. Womens Health (Larchmt) 16 (2007) 667–677. [8] G.A. Greendale, R.G. Wight, M.H. Huang, N. Avis, E.B. Gold, H. Joffe, et al., Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation, Am. J. Epidemiol. 171 (2010) 1214–1224.
Please cite this article in press as: http://dx.doi.org/10.1016/j.maturitas.2015.07.023
P.M.
Maki,
3
[9] P.M. Maki, L.H. Rubin, D. Fornelli, L. Drogos, S. Banuvar, L.P. Shulman, et al., Effects of botanicals and combined hormone therapy on cognition in postmenopausal women, Menopause 16 (2009) 1167–1177. [10] D.R. Walega, L.H. Rubin, S. Banuvar, L.P. Shulman, P.M. Maki, Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women, Menopause 21 (2014) 807–814. [11] P.M. Maki, L.L. Drogos, L.H. Rubin, S. Banuvar, L.P. Shulman, S.E. Geller, Objective hot flashes are negatively related to verbal memory performance in midlife women, Menopause 15 (2008) 848–856. [12] R.C. Thurston, H.J. Aizenstein, C.A. Derby, E. Sejdic, P.M. Maki, Menopausal hot flashes and white matter hyperintensities, Menopause June 8 (2015) [epub ahead of print]. [13] R.C. Thurston, P.M. Maki, C.A. Derby, E. Sejdic, H.J. Aizenstein, Menopausal hot flashes and the default mode network, Fertil. Steril. 103 (2015) 1572–1578, e1. [14] N.E. Avis, S.L. Crawford, G. Greendale, J.T. Bromberger, S.A. Everson-Rose, E.B. Gold, et al., Duration of menopausal vasomotor symptoms over the menopause transition, JAMA Intern. Med. 175 (2015) 531–539. [15] D.R. Meldrum, J.D. Defazio, Y. Erlik, J.K. Lu, A.F. Wolfsen, H.E. Carlson, et al., Pituitary hormones during the menopausal hot flash, Obstet. Gynecol. 64 (1984) 752–756. [16] M. Almela, V. Hidalgo, C. Villada, L. Espin, J. Gomez-Amor, A. Salvador, The impact of cortisol reactivity to acute stress on memory: sex differences in middle-aged people, Stress 14 (2011) 117–127. [17] E.W. Freeman, M.D. Sammel, L. Liu, C.R. Gracia, D.B. Nelson, L. Hollander, Hormones and menopausal status as predictors of depression in women in transition to menopause, Arch. Gen. Psychiatry 61 (2004) 62–70. [18] M.H. Trivedi, T.L. Greer, Cognitive dysfunction in unipolar depression: implications for treatment, J. Affect. Disord. 152–154 (2014) 19–27. [19] M. Roig, S. Nordbrandt, S.S. Geertsen, J.B. Nielsen, The effects of cardiovascular exercise on human memory: a review with meta-analysis, Neurosci. Biobehav. Rev. 37 (2013) 1645–1666.
Verbal
memory
and
menopause,
Maturitas
(2015),
ARTICLE IN PRESS
MAT-6458; No. of Pages 3
Maturitas xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Maturitas journal homepage: www.elsevier.com/locate/maturitas
Review article
Verbal memory and menopause Pauline M. Maki University of Illinois at Chicago, College of Medicine, Neuropsychiatric Institute (MC913), 912 South Wood Street, Chicago, Illinois 60612, USA
a r t i c l e
i n f o
Article history: Received 23 July 2015 Received in revised form 24 July 2015 Accepted 26 July 2015 Available online xxx Keywords: Menopause Memory Hormone therapy Hysterectomy Vasomotor symptoms Hot flush
a b s t r a c t Midlife women frequently report memory problems during the menopausal transition. Recent studies validate those complaints by showing significant correlations between memory complaints and performance on validated memory tasks. Longitudinal studies demonstrate modest declines in verbal memory during the menopausal transition and a likely rebound during the postmenopausal stage. Clinical studies that examine changes in memory following hormonal withdrawal and add-back hormone therapy (HT) demonstrate that estradiol plays a critical role in memory. Although memory changes are frequently attributed to menopausal symptoms, studies show that the memory problems occur during the transition even after controlling for menopausal symptoms. It is well established that self-reported vasomotor symptoms (VMS) are unrelated to objective memory performance. However, emerging evidence suggests that objectively measured VMS significantly correlate with memory performance, brain activity during rest, and white matter hyperintensities. This evidence raises important questions about whether VMS and VMS treatments might affect memory during the menopausal transition. Unfortunately, there are no clinical trials to inform our understanding of how HT affects both memory and objectively measured VMS in women in whom HT is indicated for treatment of moderate to severe VMS. In clinical practice, it is helpful to normalize memory complaints, to note that evidence suggests that memory problems are temporary, and to counsel women with significant VMS that memory might improve with treatment. © 2015 Published by Elsevier Ireland Ltd.
Contents 1. 2. 3. 4. 5. 6.
Practice points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Research agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Contributor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Verbal memory refers to memory for words, stories, and other verbal material. Since as early as 1894, a female advantage in verbal memory and other verbal tasks has been recognized and validated in empirical studies [1]. Clinical and basic science studies demonstrate sex differences in the structure and function of the hippocampus and temporal lobe that likely contribute to the female advantage [1]. Basic science studies contribute direct evidence that both activational and organizational effects of estradiol on these brain areas contribute to memory performance [1]. Evi-
Abbreviations: VMS, vasomotor symptoms; HT, hormone therapy; CEE, conjugated equine estrogen; MPA, medroxyprogesterone acetate. E-mail address: [email protected]
dence of activational effects in humans is found in studies showing declines in verbal memory following oophorectomy and treatment with gonadotropin-releasing hormone analogues (GNRHa) and improvement after supplementation with hormone therapy (HT) [2,3]. Organizational effects are supported by evidence of a female advantage in verbal memory during reproductive stages where there are only modest sex differences in circulating estradiol levels; girls outperform boys before the age of sexual maturity, and women outperform men after the onset of natural menopause and after oophorectomy [1]. If estrogen plays a role in establishing and maintaining the female advantage in verbal memory, then it stands to reason that subjective memory complaints and objective memory performance would decline during the menopausal transition. Complaints of for-
http://dx.doi.org/10.1016/j.maturitas.2015.07.023 0378-5122/© 2015 Published by Elsevier Ireland Ltd.
Please cite this article in press as: http://dx.doi.org/10.1016/j.maturitas.2015.07.023
P.M.
Maki,
Verbal
memory
and
menopause,
Maturitas
(2015),
G Model MAT-6458; No. of Pages 3
ARTICLE IN PRESS P.M. Maki / Maturitas xxx (2015) xxx–xxx
2
getfulness are common during the menopausal transition in clinical samples and in samples representative of the general population [2]. Subjective memory complaints are associated not only with menopausal stage but also with advancing age, low education, lack of full-time employment, low physical activity, hot flushes, and concentration difficulties. Among samples of midlife women, there is considerable interindividual variation in subjective complaints and objective memory outcomes, but subjective complaints nevertheless correlate significantly with memory performance [3]. Generally then, although memory complaints and memory difficulties are not universal, women who report memory problems do perform lower on memory tests. Is there any evidence that menopause stage influences memory performance? Until recently, studies suggested no such relationship, but that conclusion was based on cross-sectional studies and prospective studies that did not include premenopausal estimates of memory. Relatively recent and large longitudinal studies provide new evidence that memory does decline during the menopausal transition but appears to rebound during the postmenopausal stage [4,5]. It is unclear why memory declines during the menopausal transition and then appears to rebound. A key role for estradiol in these changes is suggested by studies showing memory declines following acute declines in estradiol with a return to baseline memory function following add-back HT [6]. A common assumption is that memory problems are due to menopausal symptoms, and indeed menopausal symptoms are related to cognitive performance [4,5]. However, declines in memory during the menopausal transition persist after controlling self-reported VMS, sleep, depression and anxiety [6,7]. Similarly, although memory declines with advancing age, age cannot explain the declines occurring during the transition because they persist after controlling for age and memory appears to rebound during the postmenopausal stage despite advancing age. Although clinical studies reveal an association between cognitive complaints and self-reported VMS as measured by questionnaires or diaries [7], performance on cognitive tests is unrelated to those measures of VMS [8]. Emerging evidence, however, suggests that objective VMS might be more sensitive to cognitive and brain outcomes. While self-reported VMS are the appropriate patient-reported outcome for clinical trials of VMS treatments, compelling evidence in support of the validity of objective VMS comes from studies showing a strong placebo effect for selfreported VMS but not objective VMS as measured by ambulatory skin conductance monitors [9,10]. In one study, verbal memory correlated significantly with the number of objective VMS, but not to the number of reported VMS [11]. Similarly, recent studies showed that objective VMS, and not subjective VMS, were related to white matter abnormalities on structural brain scans and to alterations in brain function during rest [12,13]. These initial studies suggest that VMS might represent a female-specific risk factor for memory declines during the menopausal transition. To date, there are no longitudinal studies of the relationship between objectively measured VMS and memory across the menopausal transition. Such studies are needed to directly test the hypothesis that VMS contribute to memory declines during the menopausal transition and that memory rebound as VMS improve during the postmenopausal period. More broadly, this line of research raises important questions about which women might be particularly vulnerable to memory problems as they age reproductively. This question is of considerable clinical significance given new evidence from SWAN that frequent VMS last on average of 7.4 years[14]. Clinically, this issue is particularly important for minorities, as frequent VMS last an average of 10.1 in black women and 8.9 years in Hispanics [14]. The exact mechanism underlying the relationship between VMS and memory is uncertain, though cortisol is known to rise after a hot flush [15], and cortisol contributes to memPlease cite this article in press as: http://dx.doi.org/10.1016/j.maturitas.2015.07.023
P.M.
Maki,
ory impairments [16]. Further study of the relationship between objective VMS and memory is warranted. How should clinicians address the concerns of midlife women about memory problems? First, clinicians should normalize those complaints. About 40% of women in the menopausal transition complain of forgetfulness [2]. Qualitatively, women complain that they cannot remember people’s names as easily as they could in the past, and they find that when they are trying to remember something like the name of a film it is on “the tip of their tongue” but they cannot successfully retrieve the information. Many women, particularly those with a family history of Alzheimer’s disease, fear that these memory difficulties are a sign of early dementia. In this case, it can be helpful to inform women that only 5-10% of all Alzheimer’s cases have an onset before the age of 65. However, if she experiences a decline in daily function, such as getting lost in familiar surroundings and repeating herself routinely in conversations, refer her to a neurologist for further assessment. Treating depressive symptoms might also help to improve cognition. The risk for subclinical depressive symptoms as well as major depressive disorder is elevated during the menopausal transition [17] and clinical depression is associated with memory problems [18]. It is also important to encourage patients to practice good sleep habits by refraining from using computers and mobile phones and avoiding caffeine and excess alcohol before bedtime. HT should not be used for the sole purpose of improving memory. However, women receiving HT for the treatment of VMS might experience some improvements in memory, either directly due to effects of estrogen on memory systems or indirectly due to improvement in VMS and other menopausal symptoms. Lastly, sedentary women should be encouraged to engage in cardiovascular exercise to help memory problems [19]. 1. Practice points • Do not prescribe HT for the sole purpose of improving cognition. • Advise midlife women that memory complaints are common during the menopausal transition, and memory problems appear to return to baseline during the postmenopausal period. • Advise women that dementia is rare in midlife women, and refer to a neurologist only if memory problems significantly disrupt daily function. • Advise women to practice sleep hygiene and engage in cardiovascular exercise to improve memory. 2. Research agenda • To understand why memory changes during the menopausal transition, incorporate subjective and objective measures of VMS and other menopausal symptoms into prospective studies. • Conduct clinical trials of HT on memory outcomes in women with moderate-to-severe VMS. 3. Contributor Pauline Maki is the sole author. 4. Conflict of interest Dr. Pauline Maki consults for Abbott, Noven and Pfizer. 5. Funding The author has received no funding for this article.
Verbal
memory
and
menopause,
Maturitas
(2015),
G Model MAT-6458; No. of Pages 3
ARTICLE IN PRESS P.M. Maki / Maturitas xxx (2015) xxx–xxx
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