Apathy, Genetics, and Functional Status in Persons with Alzheimer Disease

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Dissertation number AAI3590347, Accession number 2014-99120-022


Background/Significance: Alzheimer Disease (AD) is an irreversible dementia that progressively destroys cognitive and daily functioning. About 5.4 million Americans currently suffer from AD, with estimated prevalence to reach 16 million by 2050 (Alzheimer's Association, 2012). AD is often regarded with fear, as most affected individuals eventually fail to recognize loved ones, lose the ability to care for themselves, and may display negative neuropsychiatric behaviors, such as apathy. Apathy is a disorder of motivation with deficits in behavioral, emotional, and/or cognitive domains and is conceptualized as a need-driven behavior, based on the Need-Driven Dementia-Compromised Behavior Model (Algase et al., 1996). Problem: Despite the high prevalence and negative sequela associated with apathy, little is known about characteristics of persons with AD, including biologic factors that contribute to the presence and severity of apathy. Purpose: The purpose of this study was to examine the extent to which individual characteristics and social environment factors predict apathy in persons with AD and the extent to which apathy influences function. Specific Aims: 1) Examine the extent to which individual characteristics (demographics and cognitive status) and social environment factors predict the severity of apathy in persons with AD, after adjusting for AD severity and Apolipoprotein E-4 (APOE4) status, 2) Examine the extent to which variations in the Oxytocin Receptor (OXTR) gene are associated with apathy in persons with AD, and 3) Examine the extent to which severity of apathy influences functional status in persons with AD, after adjusting for AD severity. Methods: This cross-sectional descriptive study of 66 persons with moderate dementia was part of a parent study of gene-environment interactions in the symptoms of AD, in which persons with a diagnosis of possible or probable AD were recruited from the community and long-term care facilities. Instrumentation: Measures of cognition (Severe Impairment Battery [SIB]), apathy (Neuropsychiatric Inventory-Nursing Home, Apathy subscale [NPI-Apathy] and Apathy Inventory [IA]), function (Functional Assessment Staging Test [FAST] and Functional Abilities Checklist [FAC]), as well as deoxyribonucleic acid (DNA) for subsequent genotyping, were available to address these aims. Results: The majority of study participants were female, with a mean age of 85 years (SD=7.35). The prevalence of apathy ranged from 53-72%, depending on the measure of apathy. Aim 1: Multiple linear regression produced a model that explained 24.5% of the variance in apathy severity (F=2.370, p=.046). Background factor variables [main demographic variables (age, gender) and cognition (SIB total score)], function (FAST total score), and number of APOE4 alleles served as the most significant and parsimonious predictors of apathy (NPI-Apathy). Aim 2: A DNA variant within the OXTR gene (rs53576) significantly predicted 19.4% of the variance in apathy severity (NPI-Apathy) (F=3.379, p=.027), while controlling for cognitive status and number ofAPOE4 alleles. The AA genotype was associated with more severe apathy. Aim 3: Both presence of apathy and apathy severity predicted overall function as measured by FAST score, controlling for cognitive status.Implications: This study is an important step in explicating the relationship between individual characteristics, such as genetics, apathy, and functional status in persons with AD. The relationship between apathy and OXTRgenotype status must be further explored, along with the predictive ability of OXTR genotype status on apathy severity. This contribution will help to provide a foundation for the development of rigorous and tailored interventions to increase meaningful engagement, reduce apathy and increase QOL in this vulnerable population.

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