INTRODUCTION: Sleep abnormalities are highly prevalent in patients with neurodegenerative disease (NDD), often appearing in the pre-clinical stage long before cognitive decline is detected.Recent reports suggest sleep and sleep position maybe associated with activation of the metabolic clearance system of the brain.This report investigates sleep biomarkers that distinguish NDD patients from those with normal cognitive function.
METHODS: Sleep records were made with the Sleep Profiler (Advanced Brain Monitoring, Inc. Carlsbad, CA) from 45 patients diagnosed with NDD (sub-groups: Mild Cognitive Impairment=24, Alzheimer's Disease=15, Other dementia=6) and 120 age-gender matched normal cognition subjects (NC).Sixteen NDD patients were taking acetylcholinesterase inhibitors. Two night recordings were obtained for all NC subjectsand all but two of the NDD patients. Studies were auto-scored and manually reviewed for quality.Head position changes/h were based on recording time. Standard severity scoring rules were applied to the ISI, PHQ9, and GAD7. For the ESS, mild ranged from 11 to 13, moderate 14 to 16,and severe > 16. Group differences were assessed using independent t-tests and Person's Chi square.
RESULTS: OSA was more prevalent in NDD compared to the NC (p<0.05),while hypertension was greater in the NC (p=0.01). NDD patients reported significantly less hypersomnia (due to the mean values in the normal range being significantly lower than the NC (p< 0.005) but greater insomnia and depression symptoms.
The NDD group demonstrated significantly more N1 sleep and less REM sleep with increased delta and theta power. Within the NDD group, AChEls suppressed N1 theta (p < 0.05) while SSRIs had no influence on sleep architecture. The correlation between REM and N1 theta across the NDD and NC studies was 0.78 (p < 0.00001).
The NDD cohort spent significantly more sleep time in the supine position based on the percent time supine (p=0.000) and the proportion of those who sleep supine >2 h/night (p<0.000, odds ratio 3.7, 95% CI 1.8 to 7.7). No difference in frequency of supine sleep >2 h/night was observed across the MCI, AD or PD/DLB/other dementia sub-groups(all p>0.60).
The number of head position changes/h between the two groups were similar (NC 2.2 +1.1/h vs. NDD 2.1 +1.7/h, p = 0.69), providing evidence that the differences in supine time were likely not driven by decreased mobility in the NDD group. When further stratified by OSA diagnosis, the NDD group exhibited significantly more cases with long duration supine sleep than in the NC group. There was no interaction between OSA diagnosis and supine sleep >2 h/night.
A multi variable logistic analysis confirmed that both supine sleep >2 h/night (p=0.01) and the percentage of time supine (p=0.001) were associated with NDD,but not age, sex, obstructive sleep apnea or snoring.
CONCLUSIONS: The results confirmed previous reports of increased delta and theta during REM sleep in patients with NDD.
Results were consistent with previous reports that NDD had lighter, more fragmentedsleep.The increased % time supine observed in NDD is likely not a direct result of OSAor lack of mobility during sleep.There were no differences in the distributions of supine sleep in the HC without OSA vs. those being treated for OSA, or in the NDD cohort with vs. without OSA.These findings offer the intriguing possibility that head position during sleep could influence the clearance of neurotoxic proteins from the brain.