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Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia

  • Shanna L. Burke (a1), Peter Maramaldi (a2) (a3) (a4), Tamara Cadet (a2) (a3) and Walter Kukull (a5)

Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD 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 AD.


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 AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.


This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 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 Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).


Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD 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 AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

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Corresponding author
Correspondence should be addressed to: Shanna L. Burke, PhD, MSW, LICSW, Florida International University, Robert Stempel College of Public Health and Social Work, School of Social Work, Modesto A. Maidique Campus, 11200 S.W. 8th Street, AHC5 564, Miami, Florida 33199, USA. Phone: +305-348-7462. Email:
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