Abstract
BackgroundNeuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer’s disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings.MethodsThis study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD).ResultsOur study found that hallucinations were significantly more likely to occur in subjects with no APOΕ4 alleles than in subjects with two Ε4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of Ε4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H).ConclusionThese findings suggest that in AD the Ε4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a decline in cognitive function, most notably in the areas of short-term memory and learning
Because of the protective effects that have been previously reported for the apolipoprotein E (APOE)*2 allele [15], individuals with the Ε2Ε4 genotype were excluded from this analysis, including them in the analyses produced similar results to those presented below
The mean age at assessment decreased in relation to the number of APOE*4 alleles subjects possessed, from 78.1 years (SD 5.9) for those with no APOE*4 alleles to 72.8 years (SD 5.4) for those with two APOE*4 alleles, but otherwise there was no evidence of an association between the demographic variables and the number of APOE*4 alleles
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a decline in cognitive function, most notably in the areas of short-term memory and learning. Between 30% and 60% of patients who are affected with AD develop psychotic symptoms (i.e., One well-known risk factor for AD, for late-onset AD (LOAD), that may increase the risk of developing psychosis in patients with AD is the E4 allele of the apolipoprotein E (APOE) gene [1]. We systematically assessed 790 subjects with probable AD at baseline to investigate whether a relationship exists between the APOE*4 allele and four neuropsychiatric symptom (BPS) domains: hallucinations, delusions, agitation, and aberrant motor behavior. Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer’s disease (AD) and are associated with increased morbidity and mortality. Genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings
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