Graduation Year


Document Type




Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Kevin Kip, Ph.D.

Co-Major Professor

Dave Morgan, Ph.D.

Committee Member

Alfred Mbah, Ph.D.

Committee Member

Ricardo Osorio, M.D.


Beta Amyloid, Cerebrospinal Fluid, Hippocampal Atrophy, Mild Cognitive Impairment


This dissertation is a critical examination of the relationship between sleep problems and/or disorders, particularly Obstructive Sleep Apnea (OSA) and Alzheimer Disease (AD). First, I conducted an exhaustive systematic review of existing literature, and identified gaps in research that led to specific research aims. For the first aim, I conducted the first ever-published meta-analysis examining sleep, cognitive decline and AD, providing an aggregate effect of sleep on AD. Second, focusing on OSA, I conducted a study examining OSA’s effect on longitudinal changes on AD biomarkers in cognitive normal, MCI and AD subjects, using data from the Alzheimer Disease Neuroimaging Initiative (ADNI). Lastly, I conducted a review, integrating over 3 decades of research examining OSA and cognition; OSA and subsequent cognitive decline; and OSA and AD; with particular focus in appreciating the heterogeneity of OSA and its outcomes in distinct age groups.

Results and implications from my research indicate that ample evidence exists linking sleep impairments and circadian regulating mechanisms directly to clinical symptoms in AD. Sleep problems and/or disorders increases your risk of cognitive decline and AD. OSA is associated with increased AD biomarker burden over time, and effects longitudinal changes in these biomarkers, such that OSA subjects progress faster than non-OSA subjects do. OSA may be age-dependent in older adults (60 – 70 years old) and the elderly (70 years and above) and is associated with neurodegenerative diseases particularly, cognitive decline and AD. Intermittent hypoxia and sleep fragmentation are two main processes by which OSA induces neurodegenerative changes. Therefore, clinical interventions aimed at OSA, such as treatment with CPAP or dental appliances, in cognitive normal and MCI patients, could possibly slow the progression of cognitive impairment to AD.

Included in

Epidemiology Commons