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Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

ABSTRACT: BACKGROUND:There may be changes in cognitive function in women going through the menopause. The current evidence remains unclear, however, whether these changes occur over and above those of general ageing. We aimed to evaluate the potential impact of the menopause (assessed by reproductive age and hormone levels) on cognitive function in women in mid-life accounting for the underlying effects of ageing. METHODS:The study was based on the follow up of women originally enrolled in pregnancy in a birth cohort when resident in the South West of England, UK between 1991 and 1992. Using up to three repeated measurements in 2411 women (mean age 51 at first assessment), we modelled changes in six cognitive function domains: immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence and verbal fluency. The exposures of interest were reproductive age measured as years relative to the final menstrual period (FMP), chronological age and reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)). RESULTS:Processing speed (-?0.21 (95% CI -?0.36 to -?0.06) standard deviation (SD) difference per 10 years since FMP), immediate verbal episodic memory (-?0.15 (95% CI -?0.35 to 0.06)) and delayed verbal episodic memory (-?0.17 (95% CI -?0.37 to 0.03)) declined with reproductive age. Reproductive hormones were not robustly associated with processing speed, but FSH and LH were both negatively associated with immediate (-?0.08 (95% CI -?0.13 to -?0.02) SD difference per SD difference in hormone level) and delayed verbal episodic memory (-?0.08 (95% CI -?0.13 to -?0.03)). There was little consistent evidence of cognitive function declining with menopause in other cognitive domains. CONCLUSIONS:Of the cognitive domains tested only verbal episodic memory declined both in relation to age since the menopause and in conjunction with the reproductive hormones that reflect the menopause. This decline was independent of normal ageing and suggests that the menopause is associated with a mild impact on this specific domain of cognitive function.

SUBMITTER: Kilpi F

PROVIDER: S-EPMC7427852 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

Kilpi Fanny F Soares Ana Luiza G ALG Fraser Abigail A Nelson Scott M SM Sattar Naveed N Fallon Sean James SJ Tilling Kate K Lawlor Deborah A DA

BMC women's health 20200814 1

<h4>Background</h4>There may be changes in cognitive function in women going through the menopause. The current evidence remains unclear, however, whether these changes occur over and above those of general ageing. We aimed to evaluate the potential impact of the menopause (assessed by reproductive age and hormone levels) on cognitive function in women in mid-life accounting for the underlying effects of ageing.<h4>Methods</h4>The study was based on the follow up of women originally enrolled in ...[more]

PMID: 32795281

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Project description:BackgroundMuscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age.ResultsMuscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu).ConclusionsThis study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.

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Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

Publications

Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

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