Effect of APOE Genotype on Behavioral and Psychological Signs and Symptoms of Dementia

Sebastiaan Engelborghs¹, Bart Dermaut², Rudi D'Hooge¹, Anoek Symons³, Frederik Clement³, Peter Marien³, Johan Goeman³, Barbara A Pickut³, Marleen Van den Broeck², Sally Serneels², Marc Cruts², Christine Van Broeckhoven², and Peter P De Deyn¹. (1) Laboratory of Neurochemistry and Behavior, University of Antwerp / Born-Bunge Foundation, Antwerp, Belgium, (2) Department of Molecular Genetics, University of Antwerp / Born-Bunge Foundation / Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium, (3) Department of Neurology, Middelheim General Hospital, Antwerp, Belgium

Objective: The apolipoprotein E epsilon 4 (APOE E4) allele is an established risk factor for Alzheimer’s disease (AD) and has been assumed to be involved in clinical expression of AD, including that of non-cognitive symptoms. However, studies investigating possible APOE genotype effects on behavioral and psychological signs and symptoms of dementia (BPSD) in AD patients, yielded contradictory results. While some studies suggested an influence of APOE genotype on age of onset and clinical expression of frontotemporal dementia (FTD), the interaction between APOE genotype and BPSD in FTD patients has not yet been examined. To determine whether apolipoprotein (APOE) genotype influences BPSD in patients with probable AD and probable FTD, we performed the here presented analyses. Design: We set up a prospective, longitudinal study on neurobiological and genetic markers of BPSD. At present, 175 AD and 25 FTD patients have been enrolled. We here present the preliminary results of an interim analysis on APOE genotype effects on BPSD in a sample of 109 AD and 15 FTD patients.

Materials and Methods: At inclusion, all patients underwent a neuropsychological examination and behavioral assessment was performed using a battery of behavioral assessment scales (Middelheim Frontality Score, Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). Blood was collected for APOE genotyping.

Results: APOE allele frequencies for AD and FTD patients were 0.05 versus 0.13 (E2), 0.65 versus 0.67 (E3) and 0.30 versus 0.20 (E4). No significant differences could be observed comparing behavioral data of AD and FTD patients carrying at least one APOE E4 or E2 allele with noncarriers. Even when AD and FTD patients were divided into subgroups by APOE genotype or number of APOE E4 or E2 alleles, behavioral data were not significantly different comparing these subgroups. The number of APOE E4 and E2 alleles was not correlated with BPSD in AD patients. In FTD patients, the number of APOE E4 alleles was significantly correlated with frontal lobe features and signs and symptoms of anxiety.

Conclusion: Based on this interim analysis, we could not reveal any association of APOE genotype with prevalence or severity of BPSD in AD patients. In FTD patients, the number of APOE E4 alleles correlated significantly with frontal lobe features and presence of anxiety. As APOE genotyping and recruitment of patients are still in progress, we will present results of at least 200 patients at the 11th International IPA congress.