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BACKGROUND Alzheimer’s disease is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the United States, Alzheimer’s disease is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a ‘public health epidemic’ and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of Alzheimer’s disease. METHODS Utilizing data from the National Alzheimer’s Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual Alzheimer’s disease diagnosis. . Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes. RESULTS This study reinforced the association between APOE and Alzheimer’s disease. The hazard of developing Alzheimer’s disease was eight times higher for those with recent depression and the ε4 homozygote (HR=8.15 [3.70-17.95]). Among ε4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR=10.11 [4.43-23.09]). The hazard for ε4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR=6.79 [2.38-19.37]). CONCLUSION Findings suggest that sleep disturbance, depression, and APOE ε4 genotype are associated with Alzheimer’s disease during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of Alzheimer’s disease due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

Objective Alzheimer’s disease (AD) is the result of neurodegeneration, which manifests clinically as deficits in memory, thinking, and behavior. It was hypothesized that neuropsychiatric symptoms and the apolipoprotein E genotype increase the likelihood of Alzheimer’s disease development. Methods Utilizing data from the National Alzheimer’s Coordinating Center, information from evaluations of 11,453 cognitively intact participants was analyzed. Survival analysis was used to explore relationships between individual neuropsychiatric symptoms as determined by the Neuropsychiatric Inventory Questionnaire, apolipoprotein E, and eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic (additive and multiplicative) interactions. Results This study provided evidence for an increased hazard of developing AD among participants with any of the symptoms assessed by the NPI-Q. The hazard of developing AD was almost thirteen times higher for ε4 carriers with delusions and eleven times greater for those with apathy and disinhibition. Statistically significant hazards (p > 0.001) were also realized by ε4 carriers with hallucinations; agitation; depression; anxiety; elation; apathy; irritability; and motor, sleep, and appetite disturbances. Conclusions Findings suggest that neuropsychiatric symptoms are associated with eventual AD diagnosis among a group of cognitively asymptomatic participants at baseline. Many studies begin with a group of participants already impacted by AD diagnosis. The longitudinal analysis of a group of participants who, at baseline, demonstrated no observable signs of AD was a strength of this study. This investigation contributes to the literature exploring an increased hazard of AD due to potential modifiable risk factors and genetic biomarkers such as apolipoprotein E.