Gender/Sex Differences in the Association of Mild Behavioral Impairment with Cognitive Aging

Article type: Research Article

Authors: Wolfova, Katrin^{a; b; c} | Creese, Byron^d | Aarsland, Dag^{e; f} | Ismail, Zahinoor^{g; h} | Corbett, Anneⁱ | Ballard, Clive^h | Hampshire, Adam^j | Cermakova, Pavla^{b; c; *}

Affiliations: [a] Department of Psychiatry and Medical Psychology, Third Faculty of Medicine, Charles University, Prague, Czech Republic | [b] National Institute of Mental Health, Klecany, Czech Republic | [c] Department of Epidemiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic | [d] University of Exeter Medical School, College of Medicine and Health, RD&E Hospital Wonford, Exeter, UK | [e] Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK | [f] Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway | [g] Departments of Psychiatry and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada | [h] University of Exeter Medical School, College of Medicine and Health, St Luke’s Campus, University of Exeter, Exeter, UK | [i] South Cloisters, College of Medicine & Health, St Luke’s Campus, University of Exeter, Exeter, UK | [j] Faculty of Medicine, Department of Medicine, Imperial College London, London, UK

Correspondence: [*] Correspondence to: Pavla Cermakova, MD, PhD, Second Faculty of Medicine, Charles University, V Úvalu 84, 150 06 Prague 5, Czech Republic. Tel.: +420 257 296 482; E-mail: Pavla.Cermakova@lfmotol.cuni.cz.

Abstract: 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.

Keywords: Behavioral symptoms, cognition, dementia, gender differences, sex differences

DOI: 10.3233/JAD-220040

Journal: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 345-355, 2022