Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

Ferretti, Maria-Teresa; Martínková, J; Biskup, Ewelina; Benke, Thomas; Gialdini, Gino; Nedelská, Zuzana; Rauen, Katrin; Mantua, Valentina; Religa, Dorota; Hort, Jakub; Chadha, Antonella Santuccione; Schmidt, Reinhold

doi:10.1111/ene.14174

Cited by 95 publications

(56 citation statements)

References 169 publications

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“…This finding suggests that the mechanism underlying the transport of plasmalogens from the plasma to the brain is more active in young individuals and in some males. This may be relevant to the fact that elderly individuals, and particularly females, have a higher risk for Alzheimer’s disease [ 31 ]. Thus, plasmalogen transport from the plasma to the brain may be one of the factors regulating the development of plasmalogen-dependent brain diseases.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

et al. 2021

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Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.

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Section: Discussionmentioning

confidence: 99%

Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

et al. 2021

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“…As the association between cognitive performance and risk of Alzheimer's disease and related dementias is well established, 9 disparities between sexes in education are thus a potential pathway through which differences between sexes in the risk of Alzheimer's disease and related dementias are generated. 2 , 3 , 10 …”

Section: Introductionmentioning

confidence: 99%

Sex differences and the role of education in cognitive ageing: analysis of two UK-based prospective cohort studies

Bloomberg

Dugravot

Dumurgier

et al. 2021

The Lancet Public Health

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Background Previous studies have shown an excess risk of Alzheimer's disease and related dementias among women. Education is thought to have a causal association with dementia onset. We aimed to investigate the role of education in influencing sex differences in cognitive ageing. MethodsWe analysed data from two prospective cohort studies in the UK; the English Longitudinal Study of Ageing (ELSA) and the Whitehall II study, to assess sex differences in cognitive performance and cognitive decline by birth cohort (birth year 1930-38, 1939-45, or 1946-55), before and after adjustment for education, and by high and low education level. Memory was assessed using immediate recall, for which data were available from all waves of the ELSA (2002-14) and Whitehall II (1997-2015) studies. Fluency was assessed using a semantic fluency test based on an animal naming task, with data available from all waves of the Whitehall II study and waves one to five (2002-10) and wave seven (2014) of the ELSA study. Cognitive scores were standardised separately in each study based on the mean and SD of the corresponding test among participants aged 50-59 years with secondary education. Findings 15 924 participants were included from the two studies. In pooled analyses, women had better memory scores than men in all birth cohorts, irrespective of adjustment for education (eg, at age 60 years, birth cohort 1930-38, mean difference between sexes [male scores minus female scores] -0•25 SDs [95% CI -0•32 to -0•19] after adjustment for education), and in both education level groups. Memory decline was faster in men than in women (at age 60 years, birth cohort 1946-55, mean difference in 13-year change -0•15 SDs [-0•20 to -0•09]; after adjustment for education -0•14 SDs [-0•20 to -0•08]). Men had better fluency scores than women in earlier birth cohorts and in the low education group (at age 60 years, birth cohort 1930-38, mean difference 0•20 SDs [95% CI 0•05 to 0•36]); but women had better fluency scores than men in later birth cohorts and in the high education group (at age 60 years, birth cohort 1946-55, mean difference -0•17 SDs [-0•24 to -0•10]). No sex differences were observed for fluency decline.Interpretation Our findings suggest that decreasing disparities between sexes in education, due to secular increases in educational opportunities, could attenuate sex differences in dementia risk and cognitive decline in the future.

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“…33 On the other hand, the potential bene ts of HRT to prolong estrogen supply in older women have not been corroborated by interventional studies, 34,35 while the observational evidence remains con icting. 4,[36][37][38][39] The Women's Health Initiative Study (WHIS), is the only clinical trial that evaluated postmenopausal hormone therapy on preventing dementia, concluded that the risk of dementia was doubled in women randomised to estrogen-progestin based HRT. 34 In a case-control study in Finland, long-term use of systemic HRT was associated with an increased risk of Alzheimer's disease.…”

Section: Exogenous Hormone Usementioning

confidence: 99%

“…3 While the risk of developing dementia increases with age, the extent to which the female predominance is simply due to women's longer lifespan remains far from conclusive, and femalespeci c reproductive factors may be able to explain these sex disparities. 4,5 Several endogenous estrogen changes occur throughout a woman's reproductive life. Estradiol (E2) is the most predominant form of estrogen during reproductive life (from menarche to menopause) 6 and estriol (E3) is the primary estrogen during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…Few studies evaluated the long-term effect of reproductive factors on dementia risk, such that conclusions remain equivocal, and the putative mechanisms are not well-understood. 4,[8][9][10][11][12][13] This study examined the reproductive factors and exogenous hormone use in relation to the risk of incident all-cause dementia in women in the UK Biobank. We assessed whether the effects of these factors vary by age, socioeconomic status, smoking status and body mass index (BMI).…”

Section: Introductionmentioning

confidence: 99%

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Reproductive Factors and the Risk of Incident Dementia: Results From the UK Biobank

Gong¹,

Peters²,

Woodward³

2021

Preprint

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Background: To examine the risk of incident all-cause dementia associated with reproductive factors in women, and the number of children in both sexes; and whether the effects vary by age, socioeconomic status (SES), smoking status and body mass index in the UK Biobank.Methods: A total of 273,265 women and 228,966 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia.Results: Over a median of 11.3 years follow-up, 1,680 dementia were recorded in women and 2,021 in men. Adjusted HRs (95% confidence intervals (CIs)) for dementia were 1.20 (1.08, 1.35) for menarche <12 years, and 1.24 (1.10, 1.39) for menarche ≥15 years compared to 13 years; 0.86 (0.74, 1.00) for ever been pregnant; 0.80 (0.69, 0.93) for each abortion; 1.29 (1.12, 1.49) for menopause at <47 compared to 50 years; 1.13 (1.01, 1.27) for hysterectomy; 0.80 (0.72, 0.90) for oral contraceptive pills use; and 1.56 (1.40, 1.73) for hormone replacement therapy (HRT) use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes. There was evidence for early (natural and artificial) menopause, and a greater number of children were associated with a higher risk of dementia among women of relatively lower SES only.Conclusions: Shorter cumulative endogenous estrogen exposure in women is associated with higher dementia risk, although female biological factors involved in childbearing are unlikely to account for risk variation.

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Sex and gender differences in Alzheimer’s disease: current challenges and implications for clinical practice

Cited by 95 publications

References 169 publications

Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

Sex differences and the role of education in cognitive ageing: analysis of two UK-based prospective cohort studies

Reproductive Factors and the Risk of Incident Dementia: Results From the UK Biobank

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