Abstract

<h3>Objective:</h3> To investigate the relationship between sleep quality and cerebrospinal fluid (CSF) flow in individuals with Parkinson’s disease (PD). <h3>Background:</h3> Previous studies have emphasized the role of CSF circulation in the clearance of brain waste products, with recent findings demonstrating increased CSF flow during sleep. CSF circulation impairment could play a major role in neurodegenerative proteinopathies such as PD, a commonly encountered feature of which is disrupted sleep. Here, we assessed the relationship between patient-reported sleep quality and imaging assays of CSF flow. <h3>Design/Methods:</h3> Imaging and clinical assessments were completed in 23 PD participants aged 56 to 79 (M<sub>age</sub>=66.70; 16 males). The Montreal Cognitive Assessment (MoCA) and Unified Parkinson’s Disease Rating Scale (UPDRS) were administered; subjective sleep measurements were recorded using the Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) items from the Patient-Reported Outcomes Measurement Information System (PROMIS) scale. MRI phase contrast sequences quantified CSF flux (mL/min) via the cerebral aqueduct. Net CSF flow was defined as the difference between caudal and cranial flow, whereas absolute flow was calculated as the sum of total caudal and cranial flow per cardiac cycle. <h3>Results:</h3> Participants had mean MoCA scores of 24.17 (range 13–30) and UPDRS scores of 30.70 (7–59). PROMIS scores for SD and SRI were 20.14 (9–32) and 15.00 (8–24), respectively. Mean CSF measurements were 0.25 mL/min (−0.29–0.88) for net and 8.11 mL/min (3.55–16.34) for absolute flow. Higher SRI scores correlated with greater net CSF flow while awake (r=0.531, p=0.023). Additionally, SRI and age explained 73.4% of variation in absolute CSF flow in a linear regression model (F(3,15)=24.5, p&lt;0.0001). <h3>Conclusions:</h3> Self-reported sleep impairment is associated with increased CSF flow in awake individuals with PD. This study is the first to link patient-reported measures of sleep with alterations to CSF flow. These data support novel outcomes for clinical studies that improve sleep. <b>Disclosure:</b> Mr. Ponzo has nothing to disclose. Dr. Hett has nothing to disclose. Mr. Eisma has nothing to disclose. Mr. Elenberger has nothing to disclose. Mr. Song has nothing to disclose. An immediate family member of Dr. McKnight has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Deciphera. The institution of Dr. McKnight has received research support from RSNA. Dr. Considine has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MDisrupt. Dr. Considine has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Park Dietz &amp; Associates. The institution of Dr. Considine has received research support from NIH. The institution of Dr. Considine has received research support from DoD. The institution of Dr. Considine has received research support from Acadia Pharmaceuticals. Manus Donahue, 13717 has received personal compensation for serving as an employee of Alterity. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alterity. Manus Donahue, 13717 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Blood Therapeutics. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. The institution of Manus Donahue, 13717 has received research support from National Institutes of Health. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from Griffin Family Foundation. The institution of Dr. Claassen has received research support from Neurocrine. The institution of Dr. Claassen has received research support from Vaccinex. The institution of Dr. Claassen has received research support from AbbVie. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche. The institution of Dr. Claassen has received research support from Prilenia. The institution of Dr. Claassen has received research support from Neurocrine/ HSG.

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