Daytime Sleepiness Can Raise Risk of Alzheimer Disease

New research shows excessive daytime sleepiness precedes Alzheimer disease

Posted Mar 12, 2018

For some time, experts have been aware of a link between excessive daytime sleepiness (EDS) and an increased risk of dementia. However, it was unclear how this relationship played out. Does excessive daytime sleepiness precede dementia and thus increase the risk? Or, is excessive daytime sleepiness a consequence of dementia?

We have now better elucidated this relationship thanks to a study published in JAMA Neurology on March 12, 2018, titled the “Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia.”

Study Design

In a longitudinal analysis, which followed 283 patients aged 70 and older for 2 years, Carvalho and fellow researchers from the Mayo Clinic tracked β-amyloid accumulation in the brains of participants who at baseline did not have dementia. The researchers tracked this accumulation using PET scans.

designua/123RF
Source: designua/123RF

Of note, early deposition of amyloid plaques in the brain is the first sign of Alzheimer disease, which is the most common cause of dementia. This deposition happens long before the initial symptoms of Alzheimer disease manifest.

EDS was measured subjectively using sleep-quality questionnaires.

Study Results

Sixty-three (22.3 percent) of the total participants in the study had EDS, supported by observed sleep apnea. The majority of these participants (53 of 63) were men.

According to the researchers:

Baseline EDS was associated with increased longitudinal Aβ accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease.

Observed changes were most prevalent in cingulate gyrus and precuneus regions, or regions of the brain responsible for emotion, memory, and so forth.

Proposed Mechanism

According to Carvalho and co-authors, it’s unclear why excessive daytime sleepiness precedes dementia and could be due to three factors.

“It remains unclear whether EDS is a result of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers.”

First, it’s possible that increased levels of β-amyloid accumulation can be mediated by EDS. Second, sleep could clear β-amyloid through a glymphatic pathway, and EDS could lead to β-amyloid accumulation. Third, EDS could cause neurodegeneration of wakefulness-promoting centers in the brain leading to sleep-wake cycle disruption and facilitation of β-amyloid toxicity.

Clinical Implications

In an accompanying editorial, Winer and Mander highlight the possible clinical impact of this research.

“One implication of this study is that self-report of subjective sleepiness may serve as a simple but effective scientific and clinical tool in assessing AD [Alzheimer disease] risk.”

By means of quick questionnaire, clinicians could subjectively measure daytime sleepiness as an indication of the pathophysiologic risk of dementia before using expensive neuroimaging techniques.

Finally, according to the Carvalho and co-authors, the major limitation of this study is a lack of objective measures to assess sleep disturbance (for example, polysomnography) or treatment (for example, CPAP). Ultimately, more research needs to be done to further suss out these findings.

References

Carvalho, DZ, et al. Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurology. March 12, 2018. doi:10.1001/jamaneurol.2018.0049

Winer, JR, Mander, BA. Waking Up to the Importance of Sleep in the Pathogenesis of Alzheimer Disease. JAMA Neurology. March 12, 2018. doi:10.1001/jamaneurol.2018.0005