Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes.

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.
Competing Interests: Dr. Lynn Marie Trotti reports grants from NINDS/NIH during the conduction of this study and personal fees from Medscape and Oakstone for providing CME lectures. Dr. Donald L. Bliwise reports grants from the Alzheimer's Association during the conduction of this study and personal fees from Merck, Ferring, Eisai, and Jazz outside of the submitted work. Dr. Glenda L. Keating has no conflict of interests to declare. Dr. David B. Rye reports grants from NIH/NINDS during the conduction of this study and personal fees from Jazz, Harmony, and Eisai outside of the submitted work. In addition, Dr. David B. Rye has a patent (US9616070B2) issued and licensed to Balance Therapeutics and a patent (US10029-053W01) pending and licensed to Balance Therapeutics and Expansion Therapeutics. Dr. William T. Hu reports grant funding from NINDS/NIH during the conduction of this study and grants from Fujirebio US, personal fees from ViveBio LLC, Roche Diagnostics, and AARP, and nonfinancial support from Advanced Brain Monitoring outside of the submitted work. In addition, Dr. William T. Hu has a patent (US9618522B2) issued.
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