Sex-specific sleep disturbances worsen psychiatric symptoms and cognitive decline in individuals with Alzheimer's disease

Background The possible association between sleep disturbances, neuropsychiatric symptoms and progression of cognitive decline considering sex still need to be clarified. Objective The aims of the study were to evaluate the possible associations between disturbed sleep (DS) and neuropsychiatric symptoms (NPS) and to evaluate the possible association between DS, cognitive decline progression and caregiver burden focusing on sex-differences. Methods 184 participants were collected within the CATIE-AD trial. Based on the response given by the caregiver to the Neuropsychiatric Inventory, patients were classified into AD with disturbed sleep (AD-DS) or AD without disturbed sleep (ADwDS). Cognitive performance and NPS were evaluated. Progression was evaluated with the Δ-Mini-Mental State Examination (MMSE) (baseline MMSE-MMSE at 3-month follow-up). A sex stratified analysis was carried out. Results AD-DS performed worse than participants with ADwDS at all the cognitive tests. AD-DS presented more frequently depression, anxiety, aberrant motor behavior, disinhibition and eating disorders. At the sex-stratified analysis, AD-DS women were more frequently disinhibited and depressed than ADwDS. Men with AD-DS presented worse performances at several cognitive tests. Furthermore, various NPS were more frequent in men with AD-DS than in those with ADwDS, including hallucination, agitation, depression, and aberrant motor behavior. The burden was higher in caregivers of men belonging to the AD-DS group. Finally, at the linear regression, adjusting for age, education and MMSE at baseline, the presence of disturbed sleep was related to a more evident decline in MMSE in men (coeff. 2.5; 95%CI 0.72–4.29; p-value 0.006). Conclusions DS was associated with several NPS, caregiver burden and, in men, faster cognitive decline progression.