Pauline M. Maki

Cognition and mood in perimenopause: a systematic review and meta-analysis.

OBJECTIVEnIt is suggested that declines in estrogen around menopause are associated with declines in cognitive functioning as well as increased risk of depressive symptoms and depressive disorders. Existing studies of objective cognitive function and mood have differed in the criteria used to stage the menopausal transition and in the outcome measures used. The purpose of this review was to synthesize the existing studies of the relationship between menopausal stage and neuropsychological performance and depression.nnnDESIGNnA search of the literature of observational studies was performed using PubMed. Four cross-sectional studies on menopausal transition stage and cognitive function and four longitudinal studies on menopausal transition stage and risk of depression, as measured by symptom inventories and structured clinical interviews, were selected. For the cognitive outcomes, fixed effects models were used to estimate overall standardized effect sizes. For the depression outcomes, the results of group comparisons were summarized using the log odds ratio and its estimated standard error.nnnRESULTSnPostmenopausal women performed significantly worse than pre- and perimenopausal women on delayed verbal memory tasks, and significantly worse than perimenopausal women on phonemic verbal fluency tasks. Peri- and postmenopausal women were at significantly increased risk of depression, as measured by standard symptom inventories and structured clinical interviews, than premenopausal women.nnnCONCLUSIONSnThe menopausal transition is a time of increased vulnerability to cognitive declines and increased risk of depressive symptoms and depressive disorders. However, these results cannot necessarily be generalized beyond the studies included in this review. This article is part of a Special Issue entitled Menopause.

The North American Menopause Society recommendations for clinical care of midlife women

In celebration of the 25th anniversary of The North American Menopause Society (NAMS), the Society has compiled a set of key points and clinical recommendations for the care of midlife women. NAMS has always been a premier source of information about menopause for both healthcare providers and midli

Cognitive function in women with HIV: findings from the Women's Interagency HIV Study.

Objective: In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2). Methods: From 2009 to 2011, 1,521 (1,019 HIV-infected) participants from the Womens Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional. Results: The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. Conclusions: The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in well-matched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition.

Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women.

ObjectiveUncontrolled intervention studies, including studies involving breast cancer survivors, have demonstrated improvements in vasomotor symptoms (VMS) after stellate ganglion blockade (SGB) with a local anesthetic. This study presents the first randomized sham-controlled trial of SGB for the treatment of VMS. MethodsParticipants included 40 postmenopausal women, aged 30 to 70 years, with moderate to severe VMS. The study was a randomized sham-controlled trial comparing the effects of SGB versus sham injection on the frequencies of total and moderate to severe VMS, as measured by daily diaries. Image-guided SGB was performed with 5 mL of 0.5% bupivacaine. Sham injection of saline was performed in subcutaneous tissues in the neck. VMS were recorded at baseline and for 6 months thereafter. Objective VMS were recorded using ambulatory sternal skin conductance monitoring during a 24-hour period at baseline and on 3-month follow-up. ResultsThere were no significant group differences in overall VMS frequency, but the frequency of moderate to very severe VMS was reduced more in the active group compared with the sham treatment group (event rate ratio, 0.50; 95% CI, 0.35-0.71; P < 0.001). The frequency of objective VMS was also reduced to a greater degree in the SGB group than in the sham group (event rate ratio, 0.71; 95% CI, 0.64-0.99; P < 0.05). There were no study-related serious adverse events. ConclusionsSGB may provide effective treatment of VMS in women who seek nonhormonal treatments because of safety concerns and personal preference. The finding that SGB significantly reduces objectively measured VMS provides further evidence of efficacy. A larger trial is warranted to confirm these findings.

The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women

In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women’s Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (pu2009<u20090.01) and memory (pu2009<u20090.001), as well as attention (pu2009=u20090.02). Regardless of HIV status, high stress was associated with poorer performance in those cognitive domains (p’su2009<u20090.05) as well as processing speed (pu2009=u20090.01) and executive function (pu2009<u20090.01). A significant HIV by stress interaction was found only for the verbal memory domain (pu2009=u20090.02); among HIV-infected women only, high stress was associated with lower performance (p’su2009<u20090.001). That association was driven by the delayed verbal memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.

Menstrual cycle effects on cortisol responsivity and emotional retrieval following a psychosocial stressor

This article is part of a Special Issue Estradiol and cognition. Laboratory-induced stress produces elevations in cortisol and deficits in memory, especially when stress is induced immediately before retrieval of emotionally valent stimuli. Sex and sex steroids appear to influence these stress-induced outcomes, though no study has directly compared the effects of laboratory-induced stress on cortisol and emotional retrieval across the menstrual cycle. We examined the effect of psychosocial stress on cortisol responsivity and emotional retrieval in women tested during either the follicular phase (low estradiol and progesterone) or the luteal phase (higher estradiol and progesterone). Forty women (50% White; age 18-40 years) participated in the study; 20 completed the task during the luteal phase and 20 during the follicular phase. Psychosocial stress was induced with the Trier Social Stress Test (TSST). On the day before the TSST, participants learned two lists of word pairs to 100% criterion. The next day, participants recalled one list after the control condition and the other after the TSST. Women in the follicular phase, but not the luteal phase, demonstrated a significant cortisol response to the TSST. There was a stress-induced decrease in emotional retrieval following the TSST, but this effect was not modified by menstrual phase. However, regression and correlational analyses showed that individual differences in stress-induced cortisol levels were associated with impaired emotional retrieval in the follicular phase only. The present findings indicate that cortisol responsivity and the impairing effects of cortisol on emotional memory are lower when levels of estradiol and progesterone are high compared to when levels are low.

Investigation of menopausal stage and symptoms on cognition in human immunodeficiency virus-infected women

ObjectiveWe evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and human immunodeficiency virus (HIV) infection with cognition. We hypothesized that HIV-infected perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition. MethodsThis cross-sectional study included 708 HIV-infected and 278 HIV-uninfected premenopausal, perimenopausal, or postmenopausal women (64% African American; median age, 44 y) from the Women’s Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms. ResultsIn multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (P’s < 0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (P’s < 0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (P’s < 0.05). Vasomotor symptoms were associated with worse attention (P < 0.05). HIV and anxiety symptoms interacted to influence verbal learning (P’s < 0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only. ConclusionsVasomotor, depressive, and anxiety symptoms, but not menopausal stage, are associated with worse cognitive performance in both HIV-infected and HIV-uninfected women, although elevated anxiety symptoms are more associated with verbal learning deficits in HIV-infected women. Because cognitive problems can interfere with everyday functioning, including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women.

Menopausal hot flashes and white matter hyperintensities.

Objective:Hot flashes are classic symptoms of menopause. Emerging data link hot flashes to cardiovascular disease (CVD) risk, yet whether hot flashes are related to brain health is poorly understood. We examined the relationship between hot flashes (measured via physiologic monitor and self-report) and white matter hyperintensities (WMH) among midlife women. Methods:Twenty midlife women (aged 40-60 y) without clinical CVD, with an intact uterus and ovaries, and not taking hormone therapy were recruited. Women underwent 24u200ahours of ambulatory physiologic and diary hot flash monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH burden; 72u200ahours of actigraphy to quantify sleep; and a blood draw, questionnaires, and physical measures to quantify demographics and CVD risk factors. Tests of a priori hypotheses regarding relationships between physiologically monitored and self-reported wake and sleep hot flashes and WMH were conducted in linear regression models. Results:More physiologically monitored hot flashes during sleep were associated with greater WMH, controlling for age, race, and body mass index (&bgr; [SE]u200a=u200a0.0002 [0.0001], Pu200a=u200a0.03]. Findings persisted after controlling for sleep characteristics and additional CVD risk factors. No relationships were observed for self-reported hot flashes. Conclusions:More physiologically monitored hot flashes during sleep are associated with greater WMH burden among midlife women without clinical CVD. Results suggest that the relationship between hot flashes and CVD risk observed in the periphery may extend to the brain. Future work should consider the unique role of sleep hot flashes in brain health.

Verbal memory and menopause.

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.

Risk of glaucoma after early bilateral oophorectomy.

ObjectiveBecause early estrogen deficiency may increase the susceptibility of the optic nerve to glaucoma, we studied the association of early bilateral oophorectomy with glaucoma. MethodsIn the Mayo Clinic Cohort Study of Oophorectomy and Aging, we studied the risk of glaucoma by comparing women who underwent bilateral oophorectomy from 1950 to 1987 with age-matched referent women who did not undergo unilateral or bilateral oophorectomy. Glaucoma diagnostic codes were identified in the records linkage system of the Rochester Epidemiology Project. Hazard ratios (HRs) were calculated during a median follow-up of 25.5 years. Analyses were stratified by age at the time of bilateral oophorectomy (in tertiles). ResultsOf 1,044 women who underwent bilateral oophorectomy before menopause, 147 developed glaucoma. Of 1,070 referent women, 133 developed glaucoma. Women who underwent bilateral oophorectomy showed no increased risk of glaucoma in the overall group (HR, 1.12; 95% CI, 0.89-1.42). However, women who underwent oophorectomy before the age of 43 years (n = 344; first tertile) had a significantly increased risk of glaucoma (HR, 1.60; 95% CI, 1.15-2.23). The results did not change after adjustment for hypertension, obesity, diabetes, or disorders of lipid metabolism at baseline. Approximately 11% of women who had undergone bilateral oophorectomy before the age of 43 years were treated with estrogen up to the age of 50 years; however, treatment did not reduce the association (HR, 1.59; 95% CI, 0.81-3.13). ConclusionsBilateral oophorectomy before the age of 43 years may increase the risk of glaucoma, and estrogen treatment does not seem to attenuate the risk.