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

Grazia D'Onofrio, Francesco Panza, Davide Seripa, Daniele Sancarlo, Francesco Paris, Leandro Cascavilla, Maria Urbano, Carolina Gravina, Andrea Fontana, Vincenzo Solfrizzi, Fabio Pellegrini, Alberto Pilotto

Research output: Contribution to journalArticlepeer-review


Background 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. Methods 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. Results 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 ∈3/∈4 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 ∈4-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. Conclusions 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 ∈4-carrier status was associated with an increased risk of affective and apathetic syndromes.

Original languageEnglish
Pages (from-to)1062-1070
Number of pages9
JournalInternational Journal of Geriatric Psychiatry
Issue number10
Publication statusPublished - Oct 2011


  • Alzheimer's disease
  • APOE
  • apolipoprotein E
  • dementia
  • neuropsychiatric symptoms
  • neuropsychiatric syndromes

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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