Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

• Type of Material: Article
• Authors: Lynn Trotti, Emory University; Donald Bliwise, Emory University; Glenda Keating, Emory University; David Rye, Emory University; William Hu, Emory University
• Language: English
• Date: 2021-01-01
• Publisher: S. Karger AG
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by S. Karger AG, Basel
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1159/000509585
• Title of Journal or Parent Work: Dementia and Geriatric Cognitive Disorders Extra
• Volume: 11
• Issue: 1
• Start Page: 19
• End Page: 25
• Grant/Funding Information: This work was supported by the National Institutes of Health under award No. K23 NS083748 (L.M.T.), R01 NS111280 (L.M.T.), R01 NS089719 (D.B.R.), K23 AG042856 (W.T.H.), and R21 AG043885 (W.T.H.) and by the Alzheimer's Association (D.L.B.). The funders were not involved in the preparation of data or this paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
• Keywords: Dementia; Nightmares; Hypocretin; Dreams; Alzheimer disease
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.