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Background: According to Japanese law, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the COVID-19 pandemic falls under Category 2, implying that it necessitates hospitalization, isolation, and significant government participation. The category of infection was lowered to Category 5 in May 2023, meaning that individuals were going back to live their lives as they did before the COVID-19 pandemic. This study aimed to explore changes in the prevalence of non-motor symptoms over a longer four-year period, spanning before and after the COVID-19 pandemic., Methods: We conducted a questionnaire survey between January and February in the following years: 2021, 2022, 2023, and 2024., Results: The Parkinson's fatigue scale score in 2021 (mean: 35.3) increased significantly in 2022 (49.84), 2023 (49.33), and 2024 (54.71) (p < 0.001). After adjusting for baseline score using a mixed linear model with random intercept, the Parkinson's fatigue scale was significantly increased by 15.9 points (95 % CI: 10.9 to 20.9) in 2022, 13.1 points (7.9-18.3) in 2023, and 16.9 points (11.3-22.6) in 2024 independently of all potential confounders including other non-motor symptoms., Conclusions: The four years of longitudinal observation during the recurrent COVID-19 pandemic revealed that patients with PD experienced an increase in fatigue. Now, post-COVID-19 fatigue is attracting attention; however, the severity of fatigue may have already deteriorated during the period of recurrent COVID-19 pandemic., Competing Interests: Declaration of competing interest Professor Saeki received research grant from YKK AP Inc.; Ushio Inc.; Tokyo Electric Power Company; EnviroLife Research Institute Co., Ltd.; Sekisui Chemical Co., Ltd.; LIXIL Corp.; KYOCERA Corp.; ENDO Lighting Corp.; and KANEKA corp.; Nihon Chuo Juhan Co., Ltd.; and Daiwa House Industry Co., Ltd. Drs. Obayashi received research grant from YKK AP, Inc.; Ushio, Inc.; Tokyo Electric Power Company; EnviroLife Research Institute Co., Ltd.; Sekisui Chemical Co., Ltd; LIXIL Corp.; Kyocera Corp.; ENDO Lighting Corp.; and Kaneka Corp. Drs. Tai received research grant from Nihon Chuo Juhan Co. The other authors reported no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To determine the association between short-wavelength light exposure at night (LAN) power and sleep quality or melatonin levels in real-life settings., Methods: In this cross-sectional study of 580 older adults (mean age, 71.0 years), we measured short-wavelength LAN power at cornea level using an originally developed light loggers over two nights. Sleep quality and physiological melatonin levels were measured using the Pittsburgh sleep quality index (PSQI) questionnaire and overnight urinary 6-sulfatoxymelatonin excretion (UME), respectively., Results: The first and second tertile short-wavelength LAN power values obtained were 0.77 × 10 -2  μW/cm 2 and 7.0 × 10 -2  μW/cm 2 , respectively, and the overall prevalence of sleep disturbances was 34.7%. The mean UME was 1.88 ± 0.70 log μg. The mean global PSQI score and the prevalence of sleep disturbances significantly increased (P = 0.004 and 0.006, respectively) with increasing tertile groups of short-wavelength LAN power. In multivariable analysis adjusted for potential confounders, the odds ratio (OR) for sleep disturbances was significantly higher in the highest tertile group of short-wavelength LAN power compared with that in the lowest tertile group (adjusted OR, 1.90; 95% confidence interval [CI]: 1.20, 3.00; P = 0.006). In addition, UME was significantly lower in the highest tertile group of short-wavelength LAN power than that in the lowest tertile group (adjusted mean difference, -0.14 log μg; 95% CI: -0.28, -0.007; P = 0.039)., Conclusions: Although short-wavelength LAN power measured at cornea level in real-life settings seemed to be significantly low, our findings suggest that short-wavelength LAN power is significantly associated with both melatonin levels and sleep disturbance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Circadian disruptions in Parkinson's disease (PD) are characterized as amplitude reduction rather than as phase shift; however, large-scale studies evaluating circadian rhythms between PD patients and non-PD older adults have not been performed. The present study aimed to compare the circadian activity rhythm (CAR) between PD patients and non-PD older adults., Methods: In this cross-sectional study on 157 PD outpatients and 1111 community-dwelling older adults (controls), physical activity was measured using actigraphy at 1-min intervals over 6 days in PD patients and 2 days in non-PD older adults. Data were base-10 log-transformed and regretted to the sigmoidally transformed cosine curve., Results: The mean amplitude (log counts/min) and acrophase were 1.85 (SD, 0.52) and 14:19 (SD, 1:15), respectively, in the controls (n = 1111); 1.42 (0.48) and 14:24 (1:20), respectively, in the early-stage (Hoehn-Yahr I and II) PD patients (n = 95); and 1.23 (0.54) and 13:41 (1:56), respectively, in the late-stage (Hoehn-Yahr III-V) PD patients (n = 62). Multivariable analysis revealed significantly lower amplitude in the early-stage and late-stage PD groups than in the controls. The acrophase significantly advanced in the late-stage PD group than in the controls. With the advancement of PD stage, amplitude and peak significantly decreased; trough increased; acrophase and active offset advanced; and robustness weakened., Conclusions: Compared with non-PD older adults, PD patients exhibited a phase advance in CAR, along with amplitude reduction. With an advanced stage of PD, a phase advance in CAR also occurred, along with amplitude reduction and weakened robustness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Obesity and overweight are highly prevalent in individuals with bipolar disorder and are associated with a risk of developing not only physical but also mental problems. The current study aimed to determine the association between bedroom light exposure at night and obesity in individuals with bipolar disorder. This cross-sectional study enrolled 200 outpatients with bipolar disorder. The light intensity in the bedroom between bedtime and rising time was measured for seven consecutive nights using a portable photometer. Body mass index (BMI) was determined using self-reported height and weight, and obesity was defined as a BMI ≥ 25 kg/m 2 . The overall prevalence of obesity was 44%. In the multivariable logistic regression analysis adjusted for age, gender, use of psychiatric medications, sleep parameters, and physical activity, the odds ratio (OR) for obesity was significantly higher in the group exposed to an average light intensity ≥ 3 lux (n = 112) than in the group exposed to an average light intensity < 3 lux (n = 88) (OR, 2.13; 95% confidence interval, 1.19-4.21; P = 0.01). Furthermore, individuals exposed to an average light intensity ≥ 3 lux were significantly higher body weight (adjusted mean, 68.7 vs. 64.4 kg; P = 0.03) and BMI (adjusted mean, 25.6 vs. 24.2 kg/m 2 ; P = 0.04) than those exposed to an average light intensity < 3 lux. A significant association was observed between bedroom light exposure at night and obesity in patients with bipolar disorder. Further longitudinal investigations are necessary to clarify this association., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Melatonin is involved in the regulation of sleep and circadian biological rhythmicity; decreased melatonin secretion has been associated with circadian disruptions. Previous studies evaluating melatonin levels between patients with Parkinson's disease (PD) and controls without PD have found conflicting results; however, large-scale studies have not been performed. Our aim is to compare endogenous melatonin levels between patients with Parkinson's disease (PD) and non-PD older adults., Methods: In this cross-sectional study on 201 outpatients with PD and 380 community-dwelling older Japanese adults (controls), urinary 6-sulfatoxymelatonin excretion was measured to estimate endogenous melatonin levels., Results: Urinary 6-sulfatoxymelatonin excretion (UME) did not significantly differ overall between PD patients and non-PD controls, even after adjusting for age, gender, medications, sleep habits, and seasons. Among PD patients, a clear and robust dose-response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity. Compared with the lowest levodopa equivalent dose quartile group (mean levodopa equivalent dose, 132 mg/day), the highest group (mean levodopa equivalent dose, 973 mg/day) exhibited a 68% increase in UME (17.8 vs. 30.0 ng/mg cre, respectively). In addition, compared with the non-PD controls, PD patients receiving a lower levodopa equivalent dose displayed decreased UME and those receiving higher levodopa equivalent dose displayed increased UME., Conclusion: Our study suggests that melatonin levels in PD patients receiving average levodopa doses are comparable with those in older adults, even after considering confounding factors. This association was modulated by daily levodopa dose in PD patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Previous studies comparing objective sleep measures between patients with Parkinson's disease (PD) and control participants were limited by their small sample size. The purpose of this study was to compare objective sleep measures between large-scale cohorts of PD outpatients and community-based older adults., Methods: In this cross-sectional study, we measured sleep parameters for 157 PD patients using an actigraph on the non-dominant wrist for six consecutive nights (95 Hoehn-Yahr stage I/II; 62 Hoehn-Yahr stage III-V). Moreover, two consecutive nights of actigraphy were performed on 1101 community-based control participants aged ≥60 years., Results: In multivariable analysis, sleep efficiency (SE) was significantly lower in patients with late-stage PD by 17.5% [95% confidence interval: 15.3%-19.7%] and early-stage PD by 9.4% [7.6%-11.1%] compared to the controls (67.1% and 75.3% vs. 84.6%, respectively). Similar results were observed for wake after sleep onset (WASO) and fragmentation index (FI). Total sleep time and sleep onset latency (SOL) were significantly shorter in patients with late- and early-stage PD stage compared to the controls. Among PD patients, significant association trends between advancement of individual Hoehn-Yahr stages and worsened sleep measures of SE, WASO, and FI were observed independently of age, gender, levodopa equivalent dose, and motor function parameter., Conclusion: This study demonstrated significant and quantitative differences in objective sleep quality and quantity between PD patients and control participants. Furthermore, with advancement of disease stages, objectively measured sleep quality worsened in PD patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Light information received by the brain influences human circadian timing and metabolism; low-level light at night (LAN) significantly increased body mass and led to prediabetes in mice. We hypothesized that LAN exposure increases the diabetes risk in humans. The aim of the present study was to evaluate a longitudinal association between LAN exposure and the incidence of diabetes in a general population., Methods: In our prospective cohort study, bedroom light intensity was measured at 1-min intervals in 678 elderly participants without diabetes at baseline. The average light intensity recorded between bedtimes and rise times over two consecutive nights was used in the analysis., Results: During follow-up (median, 42 months), 19 of the 678 participants (mean age, 70.6 years) developed diabetes. Poisson regression models revealed that the incidence rate for diabetes was significantly higher in the LAN group (average ≥ 5 lux, N = 128) than the dark group (average < 5 lux, N = 550) (incidence rate ratio, 3.74; 95% confidence interval (CI), 1.55-9.05; p = 0.003). Further propensity score adjustments in relation to LAN produced consistent results (incidence rate ratio, 3.19; 95% CI, 1.38-7.35; p = 0.007). When the cut-off value of LAN was decreased to 3 lux, the relationship remained significant (incidence rate ratio 2.74; 95% CI, 1.19-6.33; p = 0.018)., Conclusions: Our findings suggest that LAN exposure increases the incidence of diabetes in a general elderly population. Further research involving a large cohort with new-onset diabetes is warranted to elucidate these findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Exposure to light at inappropriate times in relation to the solar cycle can disturb circadian endocrine and metabolic rhythms. Previous studies have suggested an association between light exposure at night (LAN) and obesity, an important risk factor of atherosclerosis, although it remains unclear whether LAN associates with progression of atherosclerosis. To evaluate the longitudinal association between bedroom LAN intensity and progression of carotid atherosclerosis, light intensity in the bedroom at baseline and carotid artery intima-media thickness (IMT) at baseline and follow-up were measured in 989 elderly participants (945 at baseline and 780 at a median follow-up time of 34 months). The mean age of the participants was 71.4 ± 6.9 years. The average mean and maximal carotid IMT at baseline were 0.88 ± 0.15 and 1.10 ± 0.32 mm, respectively. The median intensity of bedroom LAN was 0.68 lx (IQR, 0.07-3.29). In multivariable analysis adjusted for potential confounders, the highest LAN group exhibited a significant increase in mean carotid IMT (adjusted β, 0.028; 95% CI, 0.005-0.052; P = 0.019) compared with the lowest LAN quartile group. A similar relationship was found between LAN and maximal carotid IMT (adjusted β, 0.083; 95% CI, 0.037-0.129; P < 0.001). In conclusion, we found a clear and significant association between bedroom LAN intensity and progression of subclinical carotid atherosclerosis, which was independent of known risk factors for atherosclerosis, including age, obesity, smoking, economic status, hypertension, and diabetes. Indoor light pollution may be a potential risk factor for atherosclerosis in the general population., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the associations between pre-awake light (PAL) exposure and subjective and objective measures of sleep quality., Methods: In this cross-sectional study of 1108 elderly participants (mean age, 71.9 years), we measured bedroom light intensity using a bedside light meter for two nights and sleep quality using actigraphy and a questionnaire. PAL was determined as the 2h-average light intensity before rise time, and sleep disturbance was defined as the Pittsburgh sleep quality index score ≥6., Results: Sleep disturbance prevalence increased with increased PAL exposure (P = 0.002). In multivariable models adjusted for potential confounders, the odds ratio (OR) for sleep disturbances was significantly higher in the highest quartile PAL group (Q4) than in the lowest quartile group (Q1) (OR, 1.65; 95% CI, 1.16-2.34). This association occurred independent of post-bedtime light exposure; and was stronger in the later chronotype group (n = 556) (OR, 1.80; 95% CI, 1.05-3.09) than in the earlier chronotype group (n = 552) (OR, 1.64; 95% CI, 1.01-2.64). Actigraphic sleep efficiency in the Q4 group was significantly lower by 2.6% (95% CI, 1.3-3.8) than that in the Q1 group. Moreover, longer wake after sleep onset by 7.5 min (95% CI, 2.8-12.2) and sleep onset latency by 0.2 log min (95% CI, 0.1-0.4) were observed in the Q4 group than the Q1 group., Conclusions: Higher PAL exposure was significantly associated with a higher prevalence of sleep disturbances, independent of post-bedtime light exposure. Consistent results were observed in the actigraphy analysis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Chronic low-grade systemic inflammation increases cardiovascular risk and mortality. Subjective assessment of sleep quality in previous observational studies has demonstrated associations with biomarkers of systemic inflammation, although the results are conflicting. In this cross-sectional study on 1098 elderly individuals, circulating white blood cell (WBC) count and actigraphic sleep quality were measured as indices of systemic inflammation and objective sleep quality, respectively. Lower sleep efficiency (SE) and longer wake after sleep onset (WASO) were significantly associated with increased WBC count in females (n=581) but no significant associations were observed in the association between WBC count and all objective sleep parameters in males (n=517). The associations of lower SE and longer WASO with increased WBC count in females remained significant in multivariable models adjusted for potential confounding factors. These results indicated that a 1-standard deviation increase in SE (8.0%) and WASO (27.7min) corresponded to a 0.16×10(9)/L (95% confidence interval: 0.05 to 0.27×10(9)/L) decrease and 0.14×10(9)/L (95% confidence interval: 0.03 to 0.25×10(9)/L) increase in circulating WBC count, respectively. In contrast, total sleep time and sleep onset latency were not significantly associated with WBC count in multivariable models. In conclusion, decrease in objectively measured sleep quality was significantly associated with increased circulating WBC count in females but not males, independently of known factors related to systemic inflammation including age, obesity, smoking, hypertension, diabetes, and physical inactivity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Increased cardiovascular incidence in winter is partly explained by higher blood pressure due to cold exposure. Although higher salt intake induced by cold exposure has been reported in mice, the association remains unclear in humans. To investigate the association between salt intake and cold exposure in winter, a cross-sectional study was conducted among 860 elderly subjects (mean ± standard deviation: 72.0 ± 7.1 years). We determined ambient temperature at every 10 min according to indoor temperature measured in the subjects' home, outdoor temperature, and self-administered diary logging time spent outdoors. Salt intake was estimated by nocturnal sodium excretion rate of overnight urine collection. A 1°C lower daytime ambient temperature was significantly associated with a higher urinary sodium excretion rate by 0.07 mmol/h in the subsequent night independent of age, sex, body weight, alcohol intake, calcium channel blocker use, diabetes, household income, estimated glomerular filtration rate, daytime physical activity (p=0.02). After further adjustment for outdoor temperature and day length, the lowest tertile groups of ambient daytime temperature (10.1 ± 2.3°C) showed the nocturnal urinary sodium excretion rate was higher by 14.2% (7.62 vs. 6.54 mmol/h) compared with the highest tertile group (19.3 ± 1.8°C). Higher sodium excretion rate was associated with higher nighttime ambulatory blood pressure (p<0.01) and its lower nocturnal dipping (p<0.01). Significant association between higher salt intake and daytime cold exposure partly explain the mechanism of higher blood pressure in winter, and suggest that a reduction of cold exposure might be effective to decrease salt intake., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Difficulty in initiating sleep is an important problem because it is associated with an increased incidence of depression, diabetes, myocardial infarction, and higher all-cause mortality. Although experimental studies in controlled settings have shown that warm skin temperature of the extremities (feet and hands) before bedtime is associated with shorter sleep onset latency (SOL), evidence from real life situations is limited. We assessed the relationship between indoor temperatures in the evening (2h before bedtime) and SOL among 861 home-dwelling elderly participants. Subjective SOL was determined according to a self-administered sleep diary. Actigraphic (objective) SOL, indoor temperature, and bed temperature were simultaneously measured at participants' homes for 48h during the colder seasons (October-April). The association between evening indoor temperature and SOL was assessed using a multilevel linear regression model with random intercept for individual participants. Evening indoor temperature showed a significant inverse association with log-transformed subjective SOL (β=-0.021, P<0.01) and actigraphic SOL (β=-0.019, P<0.01), independent of potential confounders including gender, insomnia medication, evening physical activity, and bedtime. Higher bed temperature during the 2h after bedtime was significantly associated with shorter log-transformed actigraphic SOL (β=-0.028, P<0.01). These significant associations were maintained even after adjustment for evening outdoor temperature. The clinically important findings of the present study indicate that SOL may be shortened by modification of evening indoor temperature and bed temperature for 2h after bedtime., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: A significant association between nocturia and subjective sleep quality has previously been reported; however, the association between nocturia and objective sleep quality remains unclear. The purpose of this study was to evaluate the quantitative association between nocturnal voiding (NV) frequency and objective sleep quality in a large, general, elderly population., Methods: Nocturnal voiding frequency, objective sleep quality, and subjective sleep quality were measured among 1086 community-based elderly individuals using actigraphy and the Pittsburgh Sleep Quality Index (PSQI) questionnaire., Results: In multivariate analyses adjusted for potential confounding factors (such as age, gender, body mass index, medication use, renal function, bedtime, rising time, daytime physical activity, endogenous melatonin levels, and bedroom light levels), increased NV frequency, ranging from zero, one, two, three or more voids, was significantly associated with poorer objective sleep quality, including lower sleep efficiency (SE) and longer wake after sleep onset (WASO) (mean SE, 86.3, 84.8, 83.6, and 81.2%, respectively; p for trend <0.001; mean WASO: 42.6, 49.0, 53.6, and 66.1 min, respectively; p for trend <0.001), but shorter sleep onset latency (SOL) (mean SOL, 3.0, 3.0, 2.8, and 2.8 log min, respectively; p for trend = 0.018). In addition, an increased NV frequency was significantly associated with poorer subjective sleep quality in a multivariate model (mean PSQI global score, 4.60, 4.86, 5.22, and 5.48, respectively; p for trend 0.012)., Conclusion: The present study revealed a quantitative association between NV frequency and objective sleep quality in the general elderly population., (Copyright © 2015 Elsevier B.V. All rights reserved.)