Associations of Sex, Age, and Cardiometabolic Risk Profiles With Brain Structure and Cognition

Abstract

Objectives:It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause and cardiometabolic health were associated with brain structure and cognitive performance.Methods:Health, brain and abdominal magnetic resonance imaging (MRI) data from the UK Biobank cohort (men and women >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status and cardiometabolic health. We examined associations of class membership with brain volumes (total brain [TBV], grey matter [GMV], white matter [WMV], hippocampal [HV], white matter hyperintensities [WMHV]) and cognitive performance.Results:Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and they had the most positive associations with cognitive function and brain volumes. In those aged >60, but not in those aged 50-60 years, the negative associations of age with TBV, GMV and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance.Conclusions:Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status and cardiometabolic health profile.

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

“…Inflammation has been proposed as a key factor linking central adiposity and WMH load ( Lampe et al, 2019 ), and weight gain during the menopause transition involves a heightened inflammatory state ( Lee et al, 2009 , McCarthy and Raval, 2020 ). Inflammation linked to changes in hormone levels and body composition may thus be a mechanistic explanation for the higher risk of WMH in post-menopausal females ( Fatemi et al, 2018 , Sachdev et al, 2009 , Than et al, 2022 , Wen et al, 2009 ). However, the relationship between changes in adipose tissue and WM lesions within the shorter perimenopausal time window remains to be investigated.…”

“…Importantly, sex differences have been observed for the aetiology and progression of cardiometabolic risk factors ( Gerdts and Regitz-Zagrosek, 2019 , Yoshida et al, 2022 ) and their relation to the brain ( Alqarni et al, 2021 , Subramaniapillai et al, 2021 , Subramaniapillai et al, 2022 , Than et al, 2022 ), illustrating the critical need for sex-specific studies ( Miller and Spencer, 2014 , Shansky and Murphy, 2021 , Taylor et al, 2019 ). Further research is necessary to understand the complex interplay of mechanisms that contribute to risk for cardiometabolic and neurodegenerative diseases in post-menopausal females ( Christensen and Pike, 2015 ), and how preventive measures such as physical exercise and hormone replacement therapy can be optimised to moderate risk.…”

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia

“…Similarly, future studies may assess the association between cardiometabolic health and hippocampal structure. 89 This study did not identify any association between pain duration or severity and hippocampal diffusivity. However, there is dissonance in reporting pain onset and time of diagnosis, resulting in inconsistent assessment of true pain duration.…”