Sex Differences in Neuropsychiatric Symptoms of Alzheimer's Disease: The Modifying Effect of Apolipoprotein E ε4 Status

Sex differences in neuropsychiatric symptoms of Alzheimer's disease (AD) have been demonstrated in previous studies, and apolipoprotein E (ApoE) ε4 status influences psychiatric manifestations of AD. However, whether ApoE ε4 status modifies the sex differences in neuropsychiatric symptoms of AD is still unclear. In this study, sex differences in neuropsychiatric abnormalities were stratified and analyzed by ApoE ε4 status in mild AD and moderate to severe AD separately. The Clinical Dementia Rating (CDR) scale and the Neuropsychiatric Inventory (NPI) were used to assess dementia severity and neuropsychiatric symptoms. No sex differences were found in mild AD. In moderate to severe AD, among ε4 positive individuals, disinhibition was significantly more prevalent (8.0% in men versus 43.2% in women, p = 0.003) and severer (p = 0.003) in female patients. The frequency (16.0% in men versus 51.4% in women, p = 0.005) and score (p = 0.004) of irritability were of borderline significance after strict Bonferroni correction. In conclusion, this study supported the modifying effect of ApoE ε4 status on sex differences in neuropsychiatric symptoms of AD, and this modifying effect was pronounced in moderate to severe stage of AD. The interaction between gender and ApoE ε4 status should be considered in studies on neuropsychiatric symptoms of AD.