Menopause and later‐life cognition: Findings from the longest‐running population‐based birth cohort

AbstractBackgroundAlzheimer’s Disease is more common in women than men. Menopause timing and type have been linked with cognition post‐menopause, but associations with dementia risk are unclear. Within the MRC National Survey of Health and Development (NSHD), childhood cognition predicts later‐life cognition and has largely explained menopause‐cognition associations post‐menopause. We now explore to what extent childhood cognition explains menopause‐cognition associations in later‐life and whether residual associations emerge.MethodProspective questionnaires at ages 43‐54 provided menopause age (years since birth until period cessation) and type (surgical/natural). Addenbrooke’s Cognitive Examination (ACE‐III) gave a measure of cognitive state at age 69 (maximum n=913). Cognitive domains were investigated using ACE‐III sub‐domains and cognitive tasks in a neuroimaging sub‐study (age 69‐71; maximum n=246) assessing memory, executive function, attention, visuospatial function, processing speed and non‐verbal reasoning. All cognitive outcomes were standardised. Multivariable regression analyses adjusted for relevant affective, early cognitive, sociodemographic, hormonal, health and genetic covariables, with multiple imputation of missing values using chained equations.ResultsMenopause associated with the following cognitive outcomes: total ACE‐III, ACE‐III verbal fluency, ACE‐III memory, ACE‐III visuospatial function, pre‐clinical Alzheimer’s cognitive composite, response inhibition, and intra‐individual variability in reaction times. Later menopause associated with better performance, while surgical menopause associated with worse performance. After accounting for childhood cognition, associations remained between menopause age and total ACE‐III (β=.012; 95% CI .001, .023), ACE‐III visuospatial function (β=.012; 95% CI .000, .023) and response inhibition (β=.034; 95% CI .008, .061), and between menopause type and response inhibition (β=‐.368; 95% CI ‐.665, ‐.070). With full adjustments, associations persisted between menopause age and ACE‐III memory (β=.011; 95% CI .000, .023). Intra‐individual variability in reaction times also remained associated with menopause age (β=‐.049; 95% CI ‐.079, ‐.019) and type (β=.413; 95% CI .076, .750).ConclusionIn later‐life, associations emerge between menopause and cognitive domains implicated in dementia (memory, processing speed, attention). Later menopause associates with better performance and surgical menopause with worse. Associations are not fully explained by known predictors of later‐life cognition including childhood cognition and other lifetime covariables accounted for. Further exploration of the link between menopause and dementia risk in women is warranted.