Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology. Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline. Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL (Formula presented.) = 0.14, p &lt; 0.001, LDL (Formula presented.) = 0.20, p &lt; 0.001, triglycerides (Formula presented.) = 0.12, p &lt; 0.001) and HbA1c ((Formula presented.) = 0.24, p &lt; 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group ((Formula presented.) = −0.08, p &lt; 0.001), while WHR increased to a similar extent in both groups ((Formula presented.) = −0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes ((Formula presented.) range = 0.03–0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume ((Formula presented.) = −0.27, p &lt; 0.001). Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years.</p

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The effects were in general small, but could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females

Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

IntroductionThe menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology.MethodsIn this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline.ResultsPostmenopausal females showed higher levels of baseline blood lipids (HDL β = 0.14, p &lt; 0.001, LDL β = 0.20, p &lt; 0.001, triglycerides β = 0.12, p &lt; 0.001) and HbA1c (β = 0.24, p &lt; 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group (β = −0.08, p &lt; 0.001), while WHR increased to a similar extent in both groups (β = −0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes (β range = 0.03–0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume (β = −0.27, p &lt; 0.001).DiscussionOur findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years

Bilingual experience and executive control over the adult lifespan: The unsung role of biological sex

We investigated whether bilingual language experience over the lifespan buffers against age-related declines in executive control. Some studies have reported reduced age-related decline in executive control in bilingual adults, compared to monolingual adults. However, other studies have failed to find this effect. Here, we investigate this issue using an unspeeded measure of executive control, the Wisconsin Card Sort Task, in an adult lifespan sample that varied in bilingual language experience. The results suggested that women showed the greatest age-related decline across WCST measures, and were more likely than men to show improved performance with increased bilingual experience. We consider implications of this finding for advancing our understanding of the relation between bilingualism and cognition, and also the effects of biological sex on cognitive aging.Nous avons étudié si l'expérience linguistique bilingue au cours de la durée de vie contribue à lutter contre les baisses des fonctions exécutives liées à l'âge. Certaines études ont rapporté une diminution réduite des fonctions exécutives chez les adultes bilingues, relativement aux adultes monolingues. Cependant, d'autres études n'ont pas réussi à démontrer cet effet. Ici, nous étudions ce problème en utilisant une épreuve sans limite de temps mesurant les fonctions exécutives, le Wisconsin Card Sorting Test, dans un échantillon adulte variant dans expérience linguistique bilingue. Les résultats suggèrent que les femmes démontraient le plus grand déclin relatif à l'âge dans les mesures du WCST et étaient plus susceptibles que les hommes de présenter une performance améliorée avec une expérience bilingue accrue. Nous considérons les implications de cette découverte pour faire progresser notre compréhension de la relation entre le bilinguisme et la cognition, ainsi que les effets du sexe biologique sur le vieillissement cognitif

Sex and gender differences in cognitive and brain reserve: Implications for Alzheimers disease in women

Women represent (2)/(3) of the cases of Alzheimers disease (AD). Current research has focused on differential risks to explain higher rates of AD in women. However, factors that reduce risk for AD, like cognitive/brain reserve, are less well explored. We asked: what is known about sex and gender differences in how reserve mitigates risk for AD? We conducted a narrative review of the literature, with keywords: "sex/gender differences", "cognitive/brain reserve", "Alzheimers Disease", and the following cognitive reserve contributors: "education", "IQ", "occupation", "cognitive stimulation", "bilingualism", "socioeconomic status", "physical activity", "social support". Sixteen papers disaggregated their data by sex. Those papers observed sex and gender differences in reserve contributors. There is also evidence that greater reserve may be more beneficial in lowering AD risk in women, although more research is needed. We discuss how traditional reserve contributors are gendered and may not capture factors that support cognition in aging women.Funding Agencies|Canadian Consortium on Neurodegeneration and Aging; Wilfred and Joyce Posluns Chair in Womens Brain Health and Aging (the Womens Brain Health Initiative, Ontario Brain Institute); Wilfred and Joyce Posluns Chair in Womens Brain Health and Aging (Canadian Institutes of Health Research)Canadian Institutes of Health Research (CIHR); Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR) [PJT 201610-153321, GS9-171369]; Natural Science and Engineering Research CouncilNatural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2018-05761]; Alzheimers Society; Natural Science and Engineering Research CouncilNatural Sciences and Engineering Research Council of Canada (NSERC)</p

Bilingual Experience and Executive Control over the Adult Lifespan: The Role of Biological Sex

We investigated whether bilingual language experience over the lifespan impacts women and men in a manner that differentially buffers against age-related declines in executive control. To this end, we investigated whether executive control performance in a lifespan sample of adult women and men were differentially impacted by individual differences in bilingual language experience, assessed using an unspeeded measure of executive control, the Wisconsin Card Sort Test. The results suggested that women showed both the greatest degree of age-related decline across WCST measures, and a greater likelihood than men to express improved performance as a function of increased bilingual experience. We consider implications of this finding for advancing our understanding of the relation between bilingualism and cognition, and also the effects of biological sex on cognitive aging

Bilingual experience and executive control over the adult lifespan: The role of biological sex

We investigated whether bilingual language experience over the lifespan impacts women and men in a manner that differentially buffers against age-related declines in executive control. To this end, we investigated whether executive control performance in a lifespan sample of adult women and men were differentially impacted by individual differences in bilingual language experience, assessed using an unspeeded measure of executive control, the Wisconsin Card Sort Test. The results suggested that women showed both the greatest degree of age-related decline across WCST measures, and a greater likelihood than men to express improved performance as a function of increased bilingual experience. We consider implications of this finding for advancing our understanding of the relation between bilingualism and cognition, and also the effects of biological sex on cognitive aging

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan

We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve (i.e., a composite score consisting of years of education [EDU] and crystallized IQ), impacted brain activity during the encoding and retrieval of spatial and temporal contextual details

Linking menopause-related factors, depression, APOE ε4, and proxies of biological aging in the UK Biobank cohort

Background: Menopause is an endocrine aging process marking the end of females’ reproductive years. In a subset of females, postmenopausal status has been linked to accelerated aging and neurological decline. A complex interplay between reproductive-related factors, mental disorders, and genetics may influence brain function and accelerate the rate of aging in the postmenopausal phase. Methods: Using multiple regressions corrected for age, we investigated the associations between menopause-related factors (i.e., menopausal status, menopause type, age at menopause, and reproductive span) and proxies of cellular aging (leukocyte telomere length, LTL) and brain aging (white and gray matter brain age gap, BAG) in 13,780 middle- and older-aged females from the UK Biobank (age range 40 – 70). We then determined how these proxies of biological aging were associated with each other, and evaluated the effects of menopause-related factors, history of depression, and APOE ε4 genotype on BAG and LTL, examining both additive and interactive relationships. Results: We found that postmenopausal status and older age at natural menopause were linked to longer LTL and lower BAG. Surgical menopause and longer natural reproductive span were also associated with longer LTL, but not BAG. BAG and LTL were not significantly associated with each other. The greatest variance in each proxy of biological aging was most consistently explained by models with the addition of both history of depression and APOE ε4 genotype. Conclusion: Overall, this study demonstrates a complex interplay between menopause-related factors, depression, APOE ε4 genotype, and proxies of brain and cellular aging, with results potentially being influenced by a disproportionate number of healthier participants among postmenopausal females. Future longitudinal studies incorporating heterogeneous samples are an essential step towards advancing female health

Parental status and markers of brain and cellular age: A 3D convolutional network and classification study

Recent research shows prominent effects of pregnancy and the parenthood transition on structural brain characteristics in humans. Here, we present a comprehensive study of how parental status and number of children born/fathered links to markers of brain and cellular ageing in 36,323 UK Biobank participants (age range 44.57 -82.06 years; 52% female). To assess global effects of parenting on the brain, we trained a 3D convolutional neural network on T1-weighted magnetic resonance images, and estimated brain age in a held -out test set. To investigate regional specificity, we extracted cortical and subcortical volumes using FreeSurfer, and ran hierarchical clustering to group regional volumes based on covariance. Leukocyte telomere length (LTL) derived from DNA was used as a marker of cellular ageing. We employed linear regression models to assess relationships between number of children, brain age, regional brain volumes, and LTL, and included interaction terms to probe sex differences in associations. Lastly, we used the brain measures and LTL as features in binary classification models, to determine if markers of brain and cellular ageing could predict parental status. The results showed associations between a greater number of children born/fathered and younger brain age in both females and males, with stronger effects observed in females. Volume-based analyses showed maternal effects in striatal and limbic regions, which were not evident in fathers. We found no evidence for associations between number of children and LTL. Classification of parental status showed an Area under the ROC Curve (AUC) of 0.57 for the brain age model, while the models using regional brain volumes and LTL as predictors showed AUCs of 0.52. Our findings align with previous population-based studies of middle- and older-aged parents, revealing subtle but significant associations between parental experience and neuroimaging-based surrogate markers of brain health. The findings further corroborate results from longitudinal cohort studies following parents across pregnancy and postpartum, potentially indicating that the parenthood transition is associated with long -term influences on brain health.ISSN:0306-4530ISSN:1873-336