Literature Review

Preclinical Brain Amyloid Deposition Is Linked to Poor Sleep


Preclinical beta-amyloid deposition in the brains of cognitively normal volunteers was associated with poor sleep quality, but not sleep quantity, according to a study published in the May issue of JAMA Neurology.

“Our findings support the hypothesis that sleep–wake abnormalities are associated with the presence of amyloid deposition in the preclinical stage of Alzheimer’s disease,” said Yo-El Ju, MD, Assistant Professor of Neurology at Washington University in St. Louis, and her associates. “Our findings may expand the temporal window during which sleep abnormalities are identifiable and potentially modifiable in Alzheimer’s disease.”

Dr. Ju and her colleagues observed that sleep–wake problems are common in Alzheimer’s disease and that, early in its course, the disease affects brain regions and pathways important for sleep and wake mechanisms. “Even in mild cognitive impairment or very mild dementia, there are abnormalities in sleep architecture and electroencephalography measures,” said Dr. Ju.

Sleep Efficiency Was Lower in Patients With Amyloid Deposition
The investigators assessed the sleep of 142 research volunteers between ages 45 and 75 (mean age, 66) using two weeks of actigraphy and sleep diary records. They recorded total sleep time, sleep efficiency, and wake after sleep onset. Some participants had a parental history of symptomatic Alzheimer’s disease and were participating in longitudinal studies of healthy aging and dementia. All the study subjects scored 0 on the Clinical Dementia Rating.

Overall, 32 participants (22.5%) had a CSF beta-amyloid 42 level of less than 500 pg/mL, indicating a strong likelihood of amyloid deposition in the brain. These subjects had significantly worse sleep efficiency than did those without amyloid deposition (80.4% vs 83.7%). This association remained significant when the data were adjusted to correct for age, sex, and APOE e4 allele carrier status. This difference in sleep efficiency also was significant in a subgroup analysis involving only the 100 study subjects who reported that their sleep had not changed during the preceding five years.

Wake after sleep onset was significantly higher among subjects with a strong likelihood of amyloid deposition than it was among those without it (63.1 min vs 54 min). In contrast, the investigators observed no difference between the two study groups in sleep quantity.

The participants with amyloid deposition tended to spend more nonsleeping time in bed, but the trend did not reach statistical significance. Similarly, participants with amyloid deposition reported taking more naps per week, but the difference between the groups’ average number of naps was not statistically significant. “When we looked at the proportion of frequent nappers, defined as those taking naps on three or more days per week, it was significantly higher in the group with amyloid deposition, compared with the group without amyloid deposition (31.2% vs 14.7%),” stated Dr. Ju.

Does Amyloid Deposition Cause Poor Sleep?
This study could not determine causality. Amyloid deposition could cause sleep–wake disruption through several mechanisms, such as direct interference with neuronal function in areas of the brain that are crucial for sleep. Conversely, poor sleep could contribute to amyloid deposition by increasing neuronal activity to a pathologic degree. These processes likely play a role in a positive feedback loop, said the investigators.

The findings of this study lay the groundwork for future research. “Longitudinal follow-up with ongoing measurement of amyloid and sleep should enable us to begin to tease apart the details of the abnormalities in sleep that begin to occur with the onset of Alzheimer’s disease pathology, as well as the directionality of the relationship between sleep and amyloid deposition,” said Dr. Ju.

The finding that sleep disruption increases the risk of future Alzheimer’s disease would provide “an even stronger motivation to identify and treat individuals with sleep disorders, such as obstructive sleep apnea,” she concluded.

—Mary Ann Moon
IMNG Medical News

Suggested Reading
Clark CN, Warren JD. A hypnic hypothesis of Alzheimer’s disease. Neurodegener Dis. 2013 Apr 26 [Epub ahead of print].

Ju YE, McLeland JS, Toedebusch CD, et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013;70(5):587-593.

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