Psychotic Symptoms in Alzheimer's Disease and 5-HTTLPR Polymorphism of the Serotonin Transporter Gene: Evidence for an Association

Abstract

The occurrence of psychotic symptoms is common in Alzheimer's disease (AD), configuring a possibly distinguished clinical entity defined “Psychosis in Alzheimer's Disease” (AD-P). In order to investigate demographic clinical and biological variables potentially associated to the occurrence of AD-P, 148 AD patients were selected. Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) scores, socio-economic status and 5-HTTLPR and APOE gene polymorphisms were determined for each subject. AD-P patients were significantly more frequent carriers of the long (L) allele of 5-HTTLPR. The percentage of AD-P increased with the number of copies of the L-allele: 13% among S homozygote; 36% among heterozygotes; 51% among L-homozygotes. No difference resulted between AD-P and non-psychotic AD (AD-NP) in the distribution of the ε4 allele of APOE. The risk of AD-P was increased in L/L homozygous ( $\mathrm{OR}=7.25$ , $\mathit{p}=0.003$ ) and, to a lesser extent, in heterozygous ( $\mathrm{OR}=3.91$ ; $\mathit{p}=0.018$ ). Backward logistic regression analysis showed that the risk for AD-P was increased in older subjects ( $\mathrm{OR}=1.07$ ; $\mathit{p}=0.018$ ) while an increase of MMSE score was protective ( $\mathrm{OR}=0.90$ ; $\mathit{p}=0.004$ ). The occurrence of AD-P resulted significantly related to age at examination, cognitive status, and to the presence of the 5-HTTLPR L-allele.