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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 721457, 14 pages
Review Article

Neuropsychiatric Symptoms, Endophenotypes, and Syndromes in Late-Onset Alzheimer's Disease: Focus on APOE Gene

1Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, 71013 Foggia, Italy
2Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, 70121 Bari, Italy
3Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, 06100 Perugia, Italy

Received 11 October 2010; Revised 11 February 2011; Accepted 11 February 2011

Academic Editor: Christiane Reitz

Copyright © 2011 Francesco Panza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.