Apolipoprotein epsilon 4 status is associated with behavioral symptoms in nursing home residents with dementia
ABSTRACT 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.
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ABSTRACT: Background:Circadian rhythm disruption, reflected in alterations in sleep-wake activity and daytime napping behavior, is consistently reported in nursing home (NH) residents with dementia. This disruption may be reflected in day-to-day instability. The concept of allostatic load (AL), a measure of cumulative biological burden over a lifetime, may be a helpful model for understanding cortisol diurnal rhythm and daytime napping activity in this population. The purpose of this study was to examine the association between intra-individual daytime napping episodes and basal cortisol diurnal rhythm in NH residents with dementia in the context of AL.Method:Using a within-individual longitudinal design (N = 51), the authors observed and recorded daytime napping activity every 20 min for 10 hr per day across 4 consecutive days. The authors obtained saliva samples 4 times each day (upon participants' waking and within 1 hr, 6 hr, and 12 hr of participants' wake time) for cortisol analysis.Results:The authors categorized participants as high changers (HCs; day-to-day instability in napping activity) or low changers (LCs; day-to-day stability). There were no significant differences in resident characteristics between groups. There was a significant difference between HCs and LCs in napping episodes (F = 4.86, p = .03), with an interaction effect of evening cortisol on napping episodes in the HC group (F = 10.161, p = .001).Conclusions:NH residents with unstable day-to-day napping episodes are more responsive to alterations in evening cortisol, an index of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. They may also be more amenable to environmental intervention, an avenue for further research.Biological Research for Nursing 07/2012; 14(4):387-95. DOI:10.1177/1099800412451118 · 1.34 Impact Factor
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ABSTRACT: BACKGROUND: The neuroanatomy of agitation and aggression in Alzheimer's disease is not well understood. METHODS: We analyzed 24 months of Alzheimer's Disease Neuroimaging Initiative data for patients with Alzheimer's disease, mild cognitive impairment-stable, and mild cognitive impairment-converter (n = 462) using the Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale. Magnetic resonance imaging regions of interest that correlated with Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale raw scores were included in mixed-model, repeated-measures analyses of agitation and aggression over time with age, sex, apolipoprotein E ε4 status, education, and Mini-Mental State Examination score as covariates. RESULTS: Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale scores worsened in patients with Alzheimer's disease and in mild cognitive impairment-converter (P < .05; trend for mild cognitive impairment, P = .0518). Greater agitation and aggression severity was associated with greater atrophy of frontal, insular, amygdala, cingulate, and hippocampal regions of interest (P < .05). Mini-Mental State Examination score was significant in mixed-effect model repeated measures only in mild cognitive impairment-converters for posterior regions of interest. Demographics and apolipoprotein ε4 were not associated with agitation and aggression. CONCLUSIONS: Agitation and aggression in Alzheimer's disease and mild cognitive impairment is associated with neurodegeneration affecting the anterior salience network that may reduce capacity to process and regulate behaviors properly.Alzheimer's & dementia: the journal of the Alzheimer's Association 12/2012; DOI:10.1016/j.jalz.2012.10.005 · 14.48 Impact Factor
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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. METHODS: 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). RESULTS: Our study found that hallucinations were significantly more likely to occur in subjects with no APOEpsilon4 alleles than in subjects with two Epsilon4 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 Epsilon4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H). CONCLUSION: These findings suggest that in AD the Epsilon4 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.Behavioral and Brain Functions 12/2012; 8(1):62. DOI:10.1186/1744-9081-8-62 · 2.00 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.