Sex differences in cognitive trajectories and practice effects in a cohort of older Londoners: The role of risk factors

BackgroundSex differences in cognitive abilities have been reported; however, the underlying reasons remain unclear.ObjectiveTo (i) investigate sex differences in cognitive performance, (ii) evaluate the contributions of established dementia risk factors to these differences, and (iii) examine the role of non-modifiable risk factors on sex differences in cognitive performance.MethodsAmong 964 cognitively unimpaired participants (aged 60-85) of the UK CHARIOT-PRO Main Study, we assessed cross-sectional and longitudinal associations, over up to 3 years of follow-up, between sex and cognitive performance, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).ResultsSex differences, mostly favoring women were observed at baseline across almost all RBANS indices including the total scale (Cohen's d = 0.3, adjusted mean difference in score = -5.4, p < 0.001). Sex differences were observed in Practice effects (PEs), with men showing less PE in almost all cognitive domains including the total scale (adjusted 1.3, p = 0.002). Greater sex differences in PEs, were documented among the 'older' participants in two out of five cognitive domains including the immediate memory index (mean difference: older (69-85 years) group = -3.2, p = 0.002); younger (60-68 years) group = -0.8, p = 0.4). Sex differences were more pronounced among 'Apolipoprotein-Ꜫ4 -carriers' in three out of five domains including the total scale (mean difference in carriers = -2.6, p = 0.002); non-carriers = -0.7, p = 0.3).ConclusionsSex differences in cognition and PE were observed after adjusting for risk factors associated with Alzheimer's disease. Future studies should also consider the effects of sex on non-modifiable risk factors and PEs to identify potential 'masked' neuropathology.