Objectives: Alzheimer's disease (AD) dementia is a neurodegenerative condition, which leads to impairments in memory. This study predicted that sleep disturbance, depression, and anxiety increase the hazard of AD, independently and as comorbid conditions. Methods: Data from the National Alzheimer's Coordinating Center was used to analyze evaluations of 12,083 cognitively asymptomatic participants. Survival analysis was used to explore the longitudinal effect of depression, sleep disturbance, and anxiety as predictors of AD. The comorbid risk posed by depression in the last two years coupled with sleep disturbance, lifetime depression and sleep disturbance, clinician-verified depression and sleep disturbance, sleep disturbance and anxiety, depression in the last two years and anxiety, lifetime depression and anxiety, and clinician-verified depression and anxiety were also analyzed as predictors of AD through main effects and additive models. Results: Main effects models demonstrated a strong hazard of AD development for those reporting depression, sleep disturbance, and anxiety as independent symptoms. The additive effect remained significant among comorbid presentations. Conclusion: Findings suggest that sleep disturbance, depression, and anxiety are associated with AD development among cognitively asymptomatic participants. Decreasing the threat posed by psychological symptoms may be one avenue for possibly delaying onset of AD.

Background: 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. 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 AD 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 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]). Conclusion: 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.

This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300–0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012–19.08]; HR = 4.665, 95% CI [1.072–20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166–0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011–1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.