Neuropsychiatric Symptoms and Alzheimer’s Disease Severity. A Focus on Sex-Differences

Objectives: The aim of the present study was to investigate possible sex predictors in the severity of NPS in a large cohort of patients with AD and to assess the role of severity in sex-related differences in NPS. Methods: Four hundred and twenty-four participants (295 women, mean age 78.4 ± 8.3 years, mean disease duration 7.4 ± 8.5 years) were included with a diagnosis of AD according to NINCDS/ADRDA criteria. Clinical data and presence of NPS were collected from family interview, medical records, and patient interview and examination. Dementia severity was assessed using the Clinical Dementia Rating Scale (CDRS) extended version. Results: CDRS score was available for 407 participants (mean score 2.6 ± 1.1); 407 (22.1%) patients had CRDS = 1, 104 (25.5%) had CRDS = 2, 127 (31.2%) had CRDS = 3, 64 (15.7%) had CDRS = 4 and 22 (15.4%) had CDRS = 5. Apathy (85.7%), agitation or restlessness (75.1%) and paranoia (59.4%) were the most common NPS. Higher CDRS scores were associated with several neuropsychiatric features, including apathy, wandering and physical aggression. In the sex-stratified analysis, NPS were associated with more severe AD only in men. Conclusions: Our findings suggest relevant sex differences in NPS with increasing severity. Clinical implications: A timely and targeted behavioral management could improve treatment outcome.