BACKGROUND: While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied. OBJECTIVE: We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort. METHODS: We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models. RESULTS: Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15%; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36%; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females. CONCLUSION: MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier.

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway

Department of Epidemiology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Psychiatry and Medical Psychology 3rd Faculty of Medicine Charles University Prague Czech Republic

Departments of Psychiatry and Clinical Neurosciences Hotchkiss Brain Institute University of Calgary Calgary Canada

Faculty of Medicine Department of Medicine Imperial College London London UK

Institute of Psychiatry Psychology and Neuroscience King's College London London UK

National Institute of Mental Health Klecany Czech Republic

South Cloisters College of Medicine and Health St Luke's Campus University of Exeter Exeter UK

University of Exeter Medical School College of Medicine and Health RD and E Hospital Wonford Exeter UK

University of Exeter Medical School College of Medicine and Health St Luke's Campus University of Exeter Exeter UK

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Impact of Mild Behavioral Impairment on Longitudinal Changes in Cognition