Christine M Walsh1, Leslie Ruoff2, Jonathan Varbel2, Kathleen Walker3, Lea T Grinberg3, Adam L Boxer3, Joel H Kramer4, Bruce L Miller3, Thomas C Neylan5. 1. Memory & Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA. Electronic address: christine.walsh@ucsf.edu. 2. Stress & Health Research Program, Department of Mental Health, San Francisco VA Medical Center, 4150 Clement Street 116P Building 8, San Francisco, CA 94121, USA. 3. Memory & Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA. 4. Memory & Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94158, USA; Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA. 5. Stress & Health Research Program, Department of Mental Health, San Francisco VA Medical Center, 4150 Clement Street 116P Building 8, San Francisco, CA 94121, USA; Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA.
Abstract
OBJECTIVE/ BACKGROUND: The brainstem is among the first regions affected in progressive supranuclear palsy (PSP) and is part of the sleep/circadian regulation network. In two small studies, blood pressure and core body temperature circadian patterns were disrupted in PSP; however, it is unclear if circadian activity rhythms are also affected. Our objective was to perform circadian analyses of the rest-activity rhythms in PSP and determine the association with increasing disease severity. PATIENTS/ METHODS: Individuals with a clinical PSP diagnosis (n = 17; nine men) and healthy older adults (n = 17; nine men) were selected for this study. Participants wore actigraphy wristbands and completed sleep diaries for up to 14 consecutive days. Data were analyzed to assess circadian activity strength (amplitude, mesor, f-ratio), phase (acrophase), and circadian stability (intradaily variability, interdaily stability, relative amplitude). Analyses controlled for sleep fragmentation, cognition, and self-reported depression. The association between disease severity using the PSP rating scale and circadian activity rhythm disruption was assessed. RESULTS: Individuals with PSP had significantly lower circadian activity mesor (p ≤ 0.001), amplitude (p ≤ 0.001), robustness (f-ratio, p <0.01), relative amplitude (p ≤ 0.001), and interdaily stability (p ≤ 0.01), with increased intradaily variability (p <0.05). CAR remained weaker in PSP after controlling for sleep fragmentation, and again when also controlling for cognitive impairment and depression. Weaker circadian activity (mesor, amplitude, f-ratio, and relative amplitude) was associated with increased disease severity. CONCLUSIONS: Circadian activity rhythms are disrupted in individuals with PSP as compared to controls, and worsen with disease severity. This is the first study of its kind to describe circadian activity rhythms in PSP.
OBJECTIVE/ BACKGROUND: The brainstem is among the first regions affected in progressive supranuclear palsy (PSP) and is part of the sleep/circadian regulation network. In two small studies, blood pressure and core body temperature circadian patterns were disrupted in PSP; however, it is unclear if circadian activity rhythms are also affected. Our objective was to perform circadian analyses of the rest-activity rhythms in PSP and determine the association with increasing disease severity. PATIENTS/ METHODS: Individuals with a clinical PSP diagnosis (n = 17; nine men) and healthy older adults (n = 17; nine men) were selected for this study. Participants wore actigraphy wristbands and completed sleep diaries for up to 14 consecutive days. Data were analyzed to assess circadian activity strength (amplitude, mesor, f-ratio), phase (acrophase), and circadian stability (intradaily variability, interdaily stability, relative amplitude). Analyses controlled for sleep fragmentation, cognition, and self-reported depression. The association between disease severity using the PSP rating scale and circadian activity rhythm disruption was assessed. RESULTS: Individuals with PSP had significantly lower circadian activity mesor (p ≤ 0.001), amplitude (p ≤ 0.001), robustness (f-ratio, p <0.01), relative amplitude (p ≤ 0.001), and interdaily stability (p ≤ 0.01), with increased intradaily variability (p <0.05). CAR remained weaker in PSP after controlling for sleep fragmentation, and again when also controlling for cognitive impairment and depression. Weaker circadian activity (mesor, amplitude, f-ratio, and relative amplitude) was associated with increased disease severity. CONCLUSIONS: Circadian activity rhythms are disrupted in individuals with PSP as compared to controls, and worsen with disease severity. This is the first study of its kind to describe circadian activity rhythms in PSP.
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