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Is daytime sleepiness actually a warning sign for Alzheimer’s?

A recent study investigated whether sleep problems such as excessive daytime sleepiness increases the risk of developing Alzheimer’s.

Are those afternoon naps that we all enjoy, well more so as we get older, resulting in harmful consequences? An association between aging and an increase in daytime sleepiness exists but the inability to remain awake all day has been linked to cognitive decline in the elderly. Additionally, several studies have provided evidence of an association between excessive daytime sleepiness and an increased risk of dementia. Previous studies suggest that individuals with sleep problems have a 1.68 times greater risk of developing cognitive dysfunction or Alzheimer’s.

The underlying mechanisms which link excessive daytime sleepiness and the pathogenesis of Alzheimer’s remain unclear. Understanding the potential mechanisms causing sleeping problems in preclinical Alzheimer’s has important clinical implications for developing early interventions to help reduce the disease progression.

What is the role of β-amyloid?

It has been hypothesised that β-amyloid, which accumulates to form plaques in the brain which are one of the driving forces in the development of Alzheimer’s, plays an important role in the association between sleep disturbances and neurodegeneration. As sleep is proposed to help clear soluble β-amyloid, sleep disturbance is suggested to contribute instead to the accumulation of β-amyloid. Evidence has also indicated that the accumulation of β-amyloid further disrupts sleep and thereby increasing synaptic activity, a regulator of β-amyloid production. This vicious cycle therefore potentially plays a fundamental role in Alzheimer’s pathogenesis and is an important biomarker in the early preclinical stages of Alzheimer’s disease. This connection highlights the importance of understanding the underlying mechanism behind the relationship.

In a recent study published in JAMA Neurology researchers in the United States investigated whether there is an association between excessive daytime sleepiness in elderly patients without dementia and an increased vulnerability to the accumulation of β-amyloid. They carried out an analysis of 283 participants who were 70 years or older and enrolled in the Mayo Clinic Study of Aging. These participants were without dementia and completed sleep quality surveys and the Epworth Sleepiness Scale (ESS) to assess their daytime sleepiness. They also underwent a cognitive assessment and two positron emission tomography (PET) scans to detect any accumulation of β-amyloid deposits.

Excessive daytime sleepiness associated with cognitive decline

Of the 283 participants, 22.3% experienced excessive daytime sleepiness at baseline. In comparison to those who did not, these elderly individuals with baseline excessive daytime sleepiness also showed a greater β-amyloid accumulation in their PET scans over the following two-year period. These results are consistent with previous studies which suggest that elderly individuals without dementia but with excessive daytime sleepiness are more susceptible to pathological changes which are associated with cognitive decline and Alzheimer’s disease.

However, the underlying mechanisms causing these sleeping problems remain unclear. The researchers are unsure if greater sleep instability, increases and/or an overload of synaptic activity, or neurodegeneration resulted in excessive daytime sleepiness. Hence, further research to elucidate the cause is necessary as this could serve as a clinical biomarker for the early detection and treatment of sleeping problems. The early treatment of daytime sleepiness has the potential to reduce β-amyloid accumulation and thereby reducing the risk of developing Alzheimer’s in this vulnerable group.

Written by Lacey Hizartzidis, PhD

Reference: Carvalho DZ, St Louis EK, Knopman DS, Boeve BF, Lowe VJ, Roberts RO, Mielke MM, Przybelski SA, Machulda MM, Petersen RC, Jack CR Jr, Vemuri P. Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0049.



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