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Circadian Rhythm Phase Advance, Amplitude Reduction Linked to Parkinson Disease

Investigators found that phase advance was associated with late-stage PD, mostly due to active offset advance, amplitude reduction, and weakened robustness.

A cross-sectional study found that older adults with Parkinson disease (PD) showed a phase advance in circadian activity rhythm (CAR), as well as amplitude reduction, when compared with older adults without PD. 

A total of 157 patients with PD and 1111 community-dwelling older adults without PD were included in the study, with physical activity measured using wrist actigraphy. Within the control group, the mean values for amplitude and acrophase (time of day with peak activity) were 1.85 log counts/min (standard deviation [SD], 0.52) and 14:19 (SD, 1:15), respectively. For patients with PD (n = 157), investigators included those with early-stage PD (n = 95), as well as late-stage PD (n = 62), and patients were grouped according to Hoehne–Yahr stage. The mean values for amplitude and acrophase were 1.42 log counts/min (SD, 0.48) and 14:24 (SD, 1:20) for early-stage PD (Hoehne–Yahr I and II), and 1.23 log counts/min (SD, 0.54) and 13:41 (SD, 1.56) for late-stage PD (Hoehne–Yahr III to V). 

Daily physical activity was analyzed with the fitness of regression (R2) model, and it was concluded that R2 values were better in the sigmoidally transferred cosine curve for patients with PD (0.29 vs 0.21, respectively), as well as for patients who did not have PD (0.47 vs 0.35, respectively). Compared with patients without PD, the adjusted mean amplitude was lower by 0.45 log counts/min for patients with early-stage PD (95% CI, 0.35-0.56) and by 0.63 log counts/min for patients with late-stage PD (95% CI, 0.50-0.75). Adjusted mean acrophase advanced significantly by 35 minutes for those with late-stage PD (95% CI, 15-16), when compared with those without PD. 

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“To the best of our knowledge, this was the first report on the circadian activity rhythm parameters in PD patients, based on a sigmoidally transformed cosine curve, which has a better fitness of regression model of daily physical activity, compared with that for a plain cosine curve,” lead author Kenji Obayashi, MD, PhD, department of epidemiology, Nara Medical University School of Medicine, in Nara, Japan, et al wrote. “Consistent with previous evidence, our study showed amplitude reduction in the circadian activity rhythm in PD patients. Interestingly, a phase advance in circadian activity rhythm was observed in PD patients but not in the community dwelling older adults. In addition, significant phase advance, loss of robustness, and amplitude reduction of CAR were more frequent in late-stage PD than in early-stage PD.”

When compared with the control group, patients with late-stage PD had significantly higher adjusted mean trough and significantly advanced adjusted mean acrophase by 37 minutes (95% CI, 17-57). Mean active onset time was again advanced for patients with late-stage PD by 24 minutes (95% CI, 3-45), in addition to offset times by 50 minutes (95% CI, 23-77). 

Patients with PD had a mean age of 71.4 years (SD, 7.7), with patients at all 4 Hoehne–Yahr stages: stage I (n = 30), stage II (n = 65), stage III (n = 25), and stages IV/V (n = 37). The median duration of PD was 57 months (interquartile range [IQR], 33-102) and patients were taking a mean daily levodopa equivalent dose of 487.8 mg (SD, 375.9). Investigators found significant association between progression of PD stage and older age, PD duration, and daily levodopa equivalent dose. 

The study was limited due to PD diagnosis not being supported by meta-iodobenzylguanidine myocardial scintigraphy, and the potential for selection bias due to nonrandom selection of participants. The control group also did not have any patients with PD; although, patients were not examined and therefore may have included some with early-stage PD and therefore affected data. Control group participants only performed actigraphy for 2 days, compared to 6 days in patients with PD, and investigators were unable to compare robustness between the 2 groups as a result of the heterogeneity. 

Obayashi K, Saeki K, Yamagami Y, et al. Circadian activity rhythm in Parkinson’s disease: findings from the PHASE study. Published online June 29, 2021. Sleep Med. 2021;85:8-14. doi:10.1016/j.sleep.2021.06.023