The APOE polymorphism in Alzheimer's disease patients with neuropsychiatric symptoms and syndromes

Abstract

Neuropsychiatric symptoms (NPS) are a common feature of Alzheimer's disease (AD), resulting in particular AD endophenotypes. The common AD genetic risk factor apolipoprotein E (APOE) has been suggested underlying these AD endophenotypes. APOE genotyping, a comprehensive geriatric assessment (CGA), and Neuropsychiatric Inventory were performed on 322 consecutive older patients. Patients were divided into three groups: AD with NPS (N = 93), AD without NPS (N = 108), and, as a control group, patients with no cognitive impairment (NoCI: N = 121). Patients with NPS were further sub-divided in four groups according to the European Alzheimer's Disease Consortium (EADC) classification of neuropsychiatric syndromes in AD: hyperactive, psychotic, affective, and apathetic. AD patients with NPS showed a significantly higher grade of cognitive impairment, more severity stage of dementia, more disability in the activities of daily living (ADL), and the instrumental ADL than AD patients without NPS. As expected, an higher frequency of APOE ε3/ε4 genotype was observed in patients with AD, both with and without NPS, than patients with NoCI. No difference in the distribution of APOE genotypes was found between AD patients with vs. without NPS. However, in AD patients APOE ε4-carriers, there was an increased risk of affective [odds ratio (OR): 2.34, 95% confidence interval (CI): 1.19-4.58) and apathetic (OR: 2.24,95%CI: 1.19-4.22) syndromes. These findings did not suggest a significant association between APOE polymorphism and presence of NPS in AD patients. In AD patients with NPS, however, APOE ε4-carrier status was associated with an increased risk of affective and apathetic syndromes.