Dose dependent effect of APOE ɛ4 on behavioral symptoms in frontal lobe dementia

To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N = 186), frontotemporal dementia (FTD) (N = 29), mixed dementia (MXD) (N = 28), dementia with Lewy bodies (DLB) (N = 11) and Parkinson's disease dementia (PDD) (N = 7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)).In FTD patients, we identified dose dependent effects of APOE ɛ4 on the Behave-AD total and cluster aggressiveness scores. APOE ɛ2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found.In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE ɛ4 with aggression (FTD) and of APOE ɛ2 with delusions (PDD/DLB).