While the relationship of apolipoprotein E (APOE) to behavioral symptoms of dementia (BSD) has been studied in community-dwelling persons with AD, it has received limited attention within the nursing home (NH) population. The aim of this study was to examine the association between APOE genotype and BSD in NH residents using direct observation.
Thirty-six participants, aged 71-102 years, were compared using a non-randomized two-group design with continuous measures. APOE genotype was obtained by buccal swab. BSD, including restlessness, escape restraint, tapping and banging, searching and wandering, pacing and walking, and vocalization, were measured using the Modified Agitated Behavior Rating Scale. Participants were observed every 20 minutes for 12 hours per day for five days. Each participant's mean behavior scores were compared according to the presence or absence of the APOE epsilon4 allele.
Resident characteristics included a mean MMSE of 10.44 indicating moderate to severe dementia and a mean of 3.44 medical co-morbidities. Fifty-six percent of the participants had one epsilon4 allele. A significant difference was found between APOE epsilon4+/4- and mean behavioral scores (F(1,31)) = 4.40, p = 0.04). Restlessness was significantly inversely correlated with MMSE (r = -0.367, p = 0.03), but not APOE genotype. There was no significant correlation between proxy reporting and direct observation (r = 0.257, p = 0.13).
Findings indicate that the presence of the APOE epsilon4+ genotype increases the risk for BSD in NH residents with dementia. Direct observation proved a more accurate estimate of BSD than proxy report.
"One limitation of this study is that we used proxy reporting instead of direct observation to assign the presence or absence of neuropsychiatric symptoms in each of the four domains we looked at. Previous studies have shown discrepancies in the accuracy of proxy reporting for assessing behavioral symptoms of dementia patients when compared with the use of direct observation . Although direct observation would have been the preferred method, the size and nature (comprised entirely of outpatient subjects) of our observed population made this impractical. "
[Show abstract][Hide abstract] ABSTRACT: Background
Neuropsychiatric 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.
This 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).
Our 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).
These 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.
"In another report, it was noted that the presence of the ε4 allele was associated with increased combativeness, agitation, wandering, and confusion . These findings were confirmed in two other recent studies in which the APOE ε4 allele has been associated with agitation/aggressiveness using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) [26, 75], and in a recent report in which the presence of the APOE e4+ genotype increased the risk for agitated behaviour, including restlessness and vocalizations, in nursing home residents with dementia  (Table 1). However, when AD patients were subdivided according to the European Alzheimer's Disease Consortium classification of neuropsychiatric syndromes, for hyperactive syndrome, including AD patients with agitation, euphoria, disinhibition, irritability, and aberrant motor behaviour, no association was found between APOE genotypes and this neuropsychiatric syndrome, as also was found for psychotic syndrome . "
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Alzheimer's Disease 04/2011; 2011(2):721457. DOI:10.4061/2011/721457
"The genetic significance of ApoE inspired research on its potential association with the psychiatric manifestations of AD – psychosis, depression, aggression, anxiety. We have identified 37 studies evaluating this concept [19-55]. The results of these studies are summarized in Table I. "
[Show abstract][Hide abstract] ABSTRACT: Behavioural and psychological symptoms of dementia (BPSD) are present in the course of the illness in up to 90% of patients with Alzheimer's disease (AD). They are the main source of caregiver burden and one of the major factors contributing to early institutionalization. The involvement of a genetic component in BPSD aetiology seems beyond controversy, though the exact significance of particular polymorphisms is uncertain in the majority of cases. Multiple genes have been assessed for their putative influence on BPSD risk. In this paper we review the behavioural genetics of AD, particularly the importance, with respect to BPSD risk, of genes coding for apolipoprotein E and proteins involved in the process of neurotransmission: serotonin receptors, serotonin transporter, COMT, MAO-A, tryptophan hydroxylase and dopamine receptors. A general conclusion is the striking inconsistency of the findings, unsurprising in the field of psychiatric genetics. The potential reasons for such discrepancy are exhaustively discussed.
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