Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: A meta‐analysis

Abstract

AbstractBackgroundAlthough the majority of individuals with Alzheimer’s disease (AD) dementia exhibit neuropsychiatric symptoms (NPS), there is substantial heterogeneity in NPS manifestation. Sex is increasingly recognized as an important factor in explaining clinical variability within AD; yet, prior studies on sex differences in NPS have reported mixed findings. Therefore, we aimed to review the existing literature on sex differences in NPS in AD dementia using a meta‐analytic approach.MethodEffect sizes were extracted from 54 studies (N=19,730; N=12,092 females [61.3%], N=7,638 males [38.7%]). Random‐effects models were used to investigate sex differences in both NPS prevalence and severity for all studies combined, NPS total scores, and for specific NPS separately. Furthermore, meta‐regression analyses were conducted to examine the effects of study characteristics and demographic and clinical variables.ResultThe majority of the included studies were of fair quality and we found no indications of publication bias. When combining all studies, female sex was associated with overall greater NPS severity (k=17, g=0.07[0.01–0.14], p<0.05), while no sex‐related differences were observed for NPS prevalence (k=41, OR =1.07[0.89–1.28], p=0.46). Meta‐regression analyses showed that younger age (QM =6.44, p<0.05) and longer disease duration (QM =4.27, p<0.05) were associated with more prevalent NPS for females with AD dementia. Regarding specific NPS, female sex was associated with more prevalent psychotic symptoms (k=4, OR=1.62[1.12–2.33], p<0.01), aberrant motor behaviors (AMB; k=5, OR=1.61[1.15–2.25], p<0.01), depressive symptoms (k=18, OR=1.56 [1.22–1.99], p<0.001), and delusions (k=11, OR=1.56 1.27–1.92], p<0.001). In addition, female sex was related to more severe depressive symptoms (k=10, g =0.20[0.08–0.29], p<0.001), disinhibition (k=6, g=0.16[0.03–0.28], p<0.05), and AMB (k=6, g=0.14[0.01–0.27], p<0.05).ConclusionFemale sex was associated with more severe overall and specific NPS in AD dementia and a higher prevalence of specific NPS. These associations are generally not affected by study setting, measurement type, age, education, disease duration, MMSE score, and APOE status. These findings support the existing literature on sex differences in the clinical manifestation of AD, which could reflect sex‐related differences in neurobiological and psychosocial factors. Determining sex differences in NPS may guide personalized assessment and tailored treatment.