The Link Between Sleep and Alzheimer’s Disease

Sleep disturbance is a debilitating symptom present in a significant portion of dementia patients. Alzheimer’s disease (AD) is the most common form of dementia, and a large portion of AD patients have trouble sleeping. Studies have shown that up to 45% of AD patients struggle with sleep disturbances. (1) There is a positive correlation between AD severity and sleep disturbance; as AD progresses, so does the gravity of sleep disturbance in affected individuals. (2) Sleep problems often precede the onset of clinical AD, and therefore might be an indicator of disease and an important area of research. (2) 

AD is thought to be driven by the production and deposition of the amyloid-β (Aβ) peptide. (3) Research has shown that the solubility and quantity of Aβ in the brain is linked to AD development. A neurological change that precedes AD symptomatology is the conversion from soluble Aβ peptide to insoluble Aβ, and the aggregation of insoluble Aβ into amyloid plaques in the brain. The aggregation of this peptide into plaques is toxic to nerve cells and is implicated in AD development. (3) Emerging evidence suggests that there is a bidirectional relationship between Aβ accumulation, sleep quality, and AD. Sleep disruption has been shown to cause an increase in Aβ release, which increases risk of plaque formation and speeds up the onset of AD. (2) AD also triggers more amyloid plaque formation in areas of the brain which affect sleep quality, resulting in a positive feedback loop. (2) Sleep disruption may increase a patient’s risk for developing AD, and AD onset increases sleep disruption. 

After determining the relationship between sleep and AD, the next step is finding treatments to prevent AD onset. Mouse models have shown that increased sleep results in decreased amyloid plaque deposition compared to disrupted sleep, suggesting sleep improvement as a possible mechanism for treating AD. (2) Current treatments for sleep disturbances in patients with AD include pharmacological intervention, cognitive-behavioral therapy, and circadian therapy, though their efficacy is not well documented. (5) Further investigating the link between sleep and AD may be the future of AD diagnosis, preventative treatment, and research. Another diagnostic tool which is currently being developed by Esurgi is the eyeAD, which tracks eye movement in an effort to diagnose the progression of AD in patients. What are your opinions on the eyeAD and its possible implications in AD diagnosis? In combination with preventative treatments that target indicators such as sleep disturbance and other diagnostic tools such as monitoring Aβ accumulation, the eyeAD may dramatically improve the lives of patients at risk for developing AD.

Sources:

1. Peter-Derex, L., Yammine, P., Bastuji, H., & Croisile, B. (2015). Sleep and Alzheimer’s disease. Sleep Medicine Reviews, 19, 29-38. 

2. Ju, Y. S., Lucey, B. P., & Holtzman, D. M. (2013). Sleep and Alzheimer disease pathology—a bidirectional relationship. Nature Reviews Neurology, 10(2), 115-119. 

3. Murphy, M. P., & Levine, H. (2010). Alzheimer’s Disease and the Amyloid-β Peptide. Journal of Alzheimer’s Disease, 19(1), 311-323.

4. Yaffe, K., Laffan, A. M., Harrison, S. L., Redline, S., Spira, A. P., Ensrud, K. E., Stone, K. L. (2011). Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women. Jama, 306(6). 

5. Mccurry, S. M., Reynolds, C. F., Ancoli-Israel, S., Teri, L., & Vitiello, M. V. (2000). Treatment of sleep disturbance in Alzheimer’s disease. Sleep Medicine Reviews, 4(6), 603-628.