Sex and ApoE‐4 interactions on development and severity of psychosis in AD

Abstract

AbstractBackgroundNearly half of all Alzheimer’s Disease (AD) patients experiences psychosis at some point in their disease trajectory. Kim et al. (2017) found a sexual dimorphism in AD psychosis where the ε4 allele may play a larger role in influencing psychosis development in females with Lewy body (LB) pathology.MethodWe investigated the effect of sex and ApoE‐4 status on age, presence and severity of psychotic symptoms on a clinical cohort using data from the National Alzheimer’s Disease Coordinating Centre (Figure 1). The non‐psychotic group (AD‐P) was compared against each of the overlapping diagnostic groups – psychotic (AD+P), delusion (AD+D) and hallucination (AD+H).ResultWe found a significant association between ε4 homozygotes and AD+P (OR = 1.08, p =. 017) and AD+D (OR = 1.09, p = .007). There was also a significant association between ε4 heterozygotes and AD+P (OR = 1.09, p = .004) and AD+D (OR = 1.08, p = .012). In males, the likelihood of having two copies of ε4 was increased in AD+P (OR = 1.10, p = .034) and AD+D (OR = 1.13, p = .006). The likelihood of having one copy of ε4 was also increased in AD+P (OR = 1.10, p = .030) and AD+D (OR = 1.10, p = .028). In females, the likelihood of having one copy of ε4 was increased in AD+H (OR = 1.10, p = .033). Participants who were female and homozygous for ε4 had a predicted increase of 0.388 in the log‐odds of being in a more severe category for delusions (95% CI: 0.016 ‐ 0.759, p = .041) and hallucinations (95% CI: 0.011 ‐ 1.264, p = .046).ConclusionOur findings show that the presence of ApoE‐4 increases the risk of psychosis in clinically diagnosed AD patients. Moreover, there are differential associations between sex, ApoE‐4 status and psychotic manifestations. The fact that we did not find an increase risk of psychosis among female homozygous ApoE‐4 carriers may be explained by the fact that we did not stratify by Lewy body pathology (Tsuang et al., 2005).