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      Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

      review-article
      Author(s): * , , ,
      Publication date (Electronic):
      Journal: Brain Sciences
      Publisher: MDPI
      Keywords: sex differences, sex hormones, aging, cognition

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          Abstract

          Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

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          Sex modifies the APOE-related risk of developing Alzheimer disease.

          André Altmann, Lu Tian, Victor W Henderson … (2014)
          The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer's Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis. © 2014 American Neurological Association.
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            Models of visuospatial and verbal memory across the adult life span.

            Denise Park, Gary Lautenschlager, Trey Hedden … (2002)
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              Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

              Scott Neu, Judy Pa, Walter Kukull … (2017)
              It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established.
              Article 0 comments Cited 231 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Brain Sci
                Journal ID (iso-abbrev): Brain Sci
                Journal ID (publisher-id): brainsci
                Title: Brain Sciences
                Publisher: MDPI
                ISSN (Electronic): 2076-3425
                Publication date (Electronic): 28 August 2018
                Publication date Collection: September 2018
                Volume: 8
                Issue: 9
                Electronic Location Identifier: 163
                Affiliations
                Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and The Alfred Hospital, Melbourne, VIC 3004, Australia; kate.hoy@ 123456monash.edu (K.H.); natalie.thomas@ 123456monash.edu (N.T.); jayashri.kulkarni@ 123456monash.edu (J.K.)
                Author notes
                [* ]Correspondence: caroline.gurvich@ 123456monash.edu ; Tel.: +61-3-9076-6585
                Article
                Publisher ID: brainsci-08-00163
                DOI: 10.3390/brainsci8090163
                PMC ID: 6162653
                PubMed ID: 30154388
                SO-VID: 9550da94-fe34-4efa-8820-d65b6fcd732c
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 14 June 2018
                Date accepted : 23 August 2018
                Categories
                Subject: Review

                Keywords: sex differences,sex hormones,aging,cognition
                Data availability:
                Keywords: sex differences, sex hormones, aging, cognition

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