Rest-activity rhythm disruption in progressive supranuclear palsy

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; 9 men) and healthy older adults (n=17; 9 men) were recruited 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 smaller 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 to describe circadian activity rhythms in PSP.

Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy

“…It is also possible that sleep in PSP is not as disrupted as it appears on overnight PSG assessment, and that PSP has a delayed circadian rhythm, thus reducing their drive for sleep during the actual PSG assessment period. We recently described weaker circadian rhythms with unaltered circadian phase between PSP and healthy older adult controls, 15 suggesting that the previous interpretation is not valid, and that a phase difference did not contribute to the lack of sleep observed on testing. To account for possible circadian effects, we intentionally maintained the typical lights-off period for each individual participating in the current PSG study.…”

“…Sleep disturbances, in particular, subjective insomnia and daytime sleepiness, have been described in 60% of PSP baseline assessments, 14 and we have found weaker rest-activity rhythms in PSP. 15 These studies might collectively suggest that weaker nighttime and daytime rhythms may result in increased sleep during the day and decreased sleep at night. To date, there have been only two overnight polysomnography (PSG) studies investigating sleep in…”

Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

“…[ 70 ] The brainstem is one among the first regions affected in PSP and it is part of the sleep/circadian regulation network. [ 7 ] Symptoms of autonomic dysfunctions and GI dysfunction are common in patients with parkinsonian disorders such as PSP. Symptoms of autonomic dysfunction are variable, including GI, cardiovascular, urogenital, and sudomotor symptoms, and also sleep and respiratory disorders.…”

“…[ 6 ] The brainstem is one among the first regions affected in PSP and it is part of the sleep/circadian regulation network. [ 7 ] Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders such as PSP. The most frequent symptom was constipation, followed by salivation and anismus, but patients with PSP most commonly complained dysphagia.…”

Brain rhythm attractor breakdown in Alzheimer's disease: Functional and pathologic implications

“…This pattern is distinct from that of preferential strengthening or weakening of an attractor (Fig. 3), which is noted for example in progressive supranuclear palsy where hyperarousal patterns predominate across the sleep-wake cycle [127,128]. The inverse, a pattern of hypersomnolence dominance is observed in early stages of synucleinopathies, especially dementia with Lewy bodies, and is accompanied by a leftward shift in spectral power.…”