Menopause and cognitive impairment: A narrative review of current knowledge

Conde, Délio Marques; Verdade, Roberto Carmignani; Valadares, Ana Lúcia Ribeiro; Mella, Lucas Francisco Botequio; Pedro, Adriana Orcesi

doi:10.5498/wjp.v11.i8.412

Cited by 52 publications

(47 citation statements)

References 103 publications

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“…Our finding of an “S”-shaped relation between age and probability of SCD in women is in line with prior research [ 27 ]. Two large population-based prospective cohort studies in the US reported a 44% to 62% prevalence of subjective cognitive decline among women undergoing the menopausal transition [ 28 , 29 ].…”

Section: Discussionsupporting

confidence: 92%

Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015–2018 Behavioral Risk Factor Surveillance System Survey

et al. 2022

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Background Prior research indicates that at least 35% of Alzheimer’s disease and related dementia risk may be amenable to prevention. Subjective cognitive decline is often the first indication of preclinical dementia, with the risk of subsequent Alzheimer’s disease in such individuals being greater in women than men. We wished to understand how modifiable factors are associated with subjective cognitive decline, and whether differences exist by sex. Methods Data were collected from men and women (45 years and older) who completed the U.S. Behavioral Risk Factor Surveillance System Cognitive Decline Module (2015–2018), n = 216,838. We calculated population-attributable fractions for subjective cognitive decline, stratified by sex, of the following factors: limited education, deafness, social isolation, depression, smoking, physical inactivity, obesity, hypertension, and diabetes. Our models were adjusted for age, race, income, employment, marital and Veteran status, and accounted for communality among risk factors. Results The final study sample included more women (53.7%) than men, but both had a similar prevalence of subjective cognitive decline (10.6% of women versus 11.2% of men). Women and men had nearly equivalent overall population-attributable fractions to explain subjective cognitive decline (39.7% for women versus 41.3% for men). The top three contributing risk factors were social isolation, depression, and hypertension, which explained three-quarters of the overall population-attributable fraction. Conclusions While we did not identify any differences in modifiable factors between men and women contributing to subjective cognitive decline, other factors including reproductive or endocrinological health history or biological factors that interact with sex to modify risk warrant further research.

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Section: Discussionsupporting

confidence: 92%

Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015–2018 Behavioral Risk Factor Surveillance System Survey

et al. 2022

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“…In addition, previous studies have proposed that genetic variation in the serotonin receptor gene 5-HT2A is associated with the occurrence of hallucinations and delusions in patients with AD [43,44]. Also, loss of neuroprotective effects of estrogen, such as modulation of neurotransmitter synthesis, synaptic plasticity and mitochondrial activity, related to menopausal changes in women might play a role in differential manifestations of MBI symptoms [45].…”

Section: Discussionmentioning

confidence: 98%

Gender/Sex Differences in the Association of Mild Behavioral Impairment with Cognitive Aging

Wolfová

Creese

Aarsland

et al. 2022

JAD

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Background: While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied. Objective: We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort. Methods: We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models. Results: Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15% ; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36% ; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females. Conclusion: MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier.

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“…Of note, estradiol withdrawal during the transition to menopausal has been linked to rises in chronic low-grade inflammation as well as neurological and metabolic changes, which seem to promote a number of debilitating symptoms including hot flashes and night sweats, as well as mood, sleep, and cognitive disturbances ( Brinton et al, 2015 ). The UK Biobank dataset does not include information on putative menopausal symptoms at the time of cognitive testing, which could have impacted participant’ cognitive performance ( Conde et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Associations between reproductive history, hormone use, APOE ε4 genotype and cognition in middle- to older-aged women from the UK Biobank

Lindseth

Lange²,

Meer³

et al. 2023

Front. Aging Neurosci.

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IntroductionRelative to men, women are at a higher risk of developing age-related neurocognitive disorders including Alzheimer’s disease. While women’s health has historically been understudied, emerging evidence suggests that reproductive life events such as pregnancy and hormone use may influence women’s cognition later in life.MethodsWe investigated the associations between reproductive history, exogenous hormone use, apolipoprotein (APOE) ε4 genotype and cognition in 221,124 middle- to older-aged (mean age 56.2 ± 8.0 years) women from the UK Biobank. Performance on six cognitive tasks was assessed, covering four cognitive domains: episodic visual memory, numeric working memory, processing speed, and executive function.ResultsA longer reproductive span, older age at menopause, older age at first and last birth, and use of hormonal contraceptives were positively associated with cognitive performance later in life. Number of live births, hysterectomy without oophorectomy and use of hormone therapy showed mixed findings, with task-specific positive and negative associations. Effect sizes were generally small (Cohen’s d < 0.1). While APOE ε4 genotype was associated with reduced processing speed and executive functioning, in a dose-dependent manner, it did not influence the observed associations between female-specific factors and cognition.DiscussionOur findings support previous evidence of associations between a broad range of female-specific factors and cognition. The positive association between a history of hormonal contraceptive use and cognition later in life showed the largest effect sizes (max. d = 0.1). More research targeting the long-term effects of female-specific factors on cognition and age-related neurocognitive disorders including Alzheimer’s disease is crucial for a better understanding of women’s brain health and to support women’s health care.

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Menopause and cognitive impairment: A narrative review of current knowledge

Cited by 52 publications

References 103 publications

Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015–2018 Behavioral Risk Factor Surveillance System Survey

Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015–2018 Behavioral Risk Factor Surveillance System Survey

Gender/Sex Differences in the Association of Mild Behavioral Impairment with Cognitive Aging

Associations between reproductive history, hormone use, APOE ε4 genotype and cognition in middle- to older-aged women from the UK Biobank

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