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Aging, estrogens, and episodic memory in women.

ABSTRACT: To review the relation in midlife and beyond between estrogen exposures and episodic memory in women.Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years.Focused literature review, including a summary of a systematic search of clinical trials of estrogens in which outcomes included an objective measure of episodic memory.The natural menopause transition is not associated with the objective changes in episodic memory. Strong clinical trial evidence indicates that initiating estrogen-containing hormone therapy after the age of about 60 years does not benefit episodic memory. Clinical trial findings in middle-aged women before the age of 60 years are limited by smaller sample sizes and shorter treatment durations, but these also do not indicate substantial memory effects. Limited short-term evidence, however, suggests that estrogens may improve verbal memory after surgical menopause. Although hormone therapy initiation in old age increases dementia risk, observational studies raise the question of an early critical window during which midlife estrogen therapy reduces late-life Alzheimer disease. However, almost no data address whether midlife estrogen therapy affects episodic memory in old age.Episodic memory is not substantially impacted by the natural menopause transition or improved by the use of estrogen-containing hormone therapy after the age of 60 years. Further research is needed to determine whether outcomes differ after surgical menopause or whether episodic memory later in life is modified by midlife estrogenic exposures.

SUBMITTER: Henderson VW

PROVIDER: S-EPMC2791907 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Aging, estrogens, and episodic memory in women.

Henderson Victor W VW

Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology 20091201 4

<h4>Objective</h4>To review the relation in midlife and beyond between estrogen exposures and episodic memory in women.<h4>Background</h4>Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years.<h4>Method</h4>Focused literature review, ...[more]

PMID: 19996872

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Project description:OBJECTIVEFew have characterized cognitive changes with age as a function of menopausal stage relative to men, or sex differences in components of memory in early midlife. The study aim was to investigate variation in memory function in early midlife as a function of sex, sex steroid hormones, and reproductive status.METHODSA total of 212 men and women aged 45 to 55 were selected for this cross-sectional study from a prenatal cohort of pregnancies whose mothers were originally recruited in 1959 to 1966. They underwent clinical and cognitive testing and hormonal assessments of menopause status. Multivariate general linear models for multiple memory outcomes were used to test hypotheses controlling for potential confounders. Episodic memory, executive function, semantic processing, and estimated verbal intelligence were assessed. Associative memory and episodic verbal memory were assessed using Face-Name Associative Memory Exam (FNAME) and Selective Reminding Test (SRT), given increased sensitivity to detecting early cognitive decline. Impacts of sex and reproductive stage on performance were tested.RESULTSWomen outperformed men on all memory measures including FNAME (??=?-0.30, P < 0.0001) and SRT (??=?-0.29, P?<?0.0001). Furthermore, premenopausal and perimenopausal women outperformed postmenopausal women on FNAME (initial learning, ?= 0.32, P?=?0.01) and SRT (recall, ?= 2.39, P?=?0.02). Across all women, higher estradiol was associated with better SRT performance (recall, ??=?1.96, P?=?0.01) and marginally associated with FNAME (initial learning, ??=?0.19, P?=?0.06).CONCLUSIONSThis study demonstrated that, in early midlife, women outperformed age-matched men across all memory measures, but sex differences were attenuated for postmenopausal women. Initial learning and memory retrieval were particularly vulnerable, whereas memory consolidation and storage were preserved. Findings underscore the significance of the decline in ovarian estradiol production in midlife and its role in shaping memory function.

Project description:Both social and genetic factors contribute to cognitive impairment and decline, yet genetic factors identified through genome-wide association studies (GWAS) explain only a small portion of trait variability. This "missing heritability" may be due to rare, potentially functional, genetic variants not assessed by GWAS, as well as gene-by-social factor interactions not explicitly modeled. Gene-by-social factor interactions may also operate differently across race/ethnic groups. We selected 39 genes that had significant, replicated associations with cognition, dementia, and related traits in published GWAS. Using gene-based analysis (SKAT/iSKAT), we tested whether common and/or rare variants were associated with episodic memory performance and decline either alone or through interaction with education in >10,000 European ancestry (EA) and >2200 African ancestry (AA) respondents from the Health and Retirement Study (HRS). Nine genes in EA and five genes in AA were associated with memory performance or decline (p < 0.05), and these effects did not attenuate after adjusting for education. Interaction between education and CLPTM1 on memory performance was significant in AA (p = 0.003; FDR-adjusted p = 0.038) and nominally significant in EA (p = 0.026). In both ethnicities, low memory performance was associated with CLPTM1 genotype (rs10416261) only for those with less than high school education, and effects persisted after adjusting for APOE ε4. For over 70% of gene-by-education interactions across the genome that were at least nominally significant in either ethnic group (p < 0.05), genetic effects were only observed for those with less than high school education. These results suggest that genetic effects on memory identified in this study are not mediated by education, but there may be important gene-by-education interactions across the genome, including in the broader APOE genomic region, which operate independently of APOE ε4. This work illustrates the importance of developing theoretical frameworks and methodological approaches for integrating social and genomic data to study cognition across ethnic groups.

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Aging, estrogens, and episodic memory in women.

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Aging, estrogens, and episodic memory in women.

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