Abstract
Introduction
The cumulative number of patients has increased through the four waves of the pandemic in Japan. Many people experienced mental stress due to the fear of infection, and restrictions of leaving the house and leisure activities. No longitudinal study has assessed the fluctuation of neuropsychiatric symptoms during the COVID-19 pandemic using the same scale. We examined changes in non-motor symptoms, and the scores of a Parkinson’s Disease (PD)-specific questionnaire between the early and later periods during the COVID-19 pandemic.
Methods
We conducted a questionnaire survey during the first wave (from February to April 2020) and the fourth wave of the COVID-19 pandemic (from March to April 2021). We compared the number of symptoms from the two periods.
Results
Compared with the first wave, the Geriatric Depression Scale score was significantly higher in the fourth wave of the pandemic (median score of GDS: 4.00 vs. 5.50, p = 0.022). Consistently, the scores of symptoms on MDS-UPDRS part 1 in the fourth wave were significantly higher in hygiene (p = 0.033), handwriting (p = 0.033), performing hobbies and other activities (p = 0.035), and turning in bed (p = 0.046) than in the first wave.
Conclusions
Our observation over a year between the early and later phases of the COVID-19 pandemic showed an increase in the severity of depression in patients with PD.
Keywords: Parkinson’s disease, Coronavirus, Depression, COVID-19 pandemic, SARS-CoV-2
1. Introduction
Nara is a local commuter town in Japan. The first wave of the COVID-19 pandemic occurred in Nara in April 2020, and a state of emergency was declared in Japan. The state included self-strict regulations, such as staying at home and refraining from going out as much as possible, wearing a mask, and avoiding three conditions: (1) closed spaces (sealed spaces with poor ventilation), 2) crowded places (many people are crowded together), and 3) close-contact settings (conversations within reach of each other, utterance is made). Since then, the cumulative number of patients has increased through the four waves of the pandemic in Japan (Fig. 1). During the repeated COVID-19 waves, many people experienced mental stress due to the fear of infection, and restrictions of leaving the house and leisure activities. Patients with Parkinson's disease (PD) may be at a higher risk of developing neuropsychiatric symptoms because they have difficulties adapting to a drastic change in the environment due to impaired functioning of the dopaminergic system [1]. Previous cross-sectional studies have shown an increase in neuropsychiatric symptoms after the COVID-19 pandemic [2] and after the lockdowns [3], [4], [5]. To our knowledge, no longitudinal study has assessed the fluctuation of neuropsychiatric symptoms during the COVID-19 pandemic using the same scale. We examined changes in non-motor symptoms, including depression, apathy, fatigue, and the scores of a PD-specific questionnaire between the early and later periods during the COVID-19 pandemic.
Fig. 1.
The cumulative number of patients has increased through the four waves of the pandemic in Nara, Japan.
2. Material and methods
2.1. Study population
We launched a prospective cohort study among 202 PD patients who were enrolled in the PHASE study (Parkinson's disease and the relationships with circadian biological rhythms and sleep). Consecutive patients fulfilled the UK Parkinson’s Disease Society Brain Bank criteria [6]. The study participants were divided into a first cohort (n = 161) and a second cohort (n = 41) depending on the timing of the baseline survey. These patients had none of the following conditions at baseline: possible or probable multiple system atrophy according to the Gilman criteria [7]; progressive supranuclear palsy according to the National Institute of Neurologic Disorders and Stroke-SPSP diagnostic criteria [8]; dementia with Lewy bodies as per McKeith and colleagues [9]; any other atypical parkinsonian syndrome such as vascular parkinsonism; or large vessel disease, infarction, or tumors on magnetic resonance imaging. The present study includes 22 patients of the second cohort who completed a questionnaire survey about psychiatric symptoms both in the first and the fourth wave of the COVID-19 pandemic. The timing of the survey of the first wave was when 3 years passed since the inspection of the PHASE study. Until the fourth wave of the COVID-19 pandemic, we excluded 19 patients from this study due to death (n = 5), bone fractures (n = 4), aspiration pneumonia (n = 1), unable to follow our instructions due to dementia (n = 6), and three patients who did not respond to the questionnaire. We identified that the enrolled 22 patients had not been infected with coronavirus-2 (SARS-CoV-2) infection when these patients visited our hospital after the fourth wave of the COVID-19 pandemic. No patient underwent surgical interventions, including deep brain stimulation surgery.
2.2. Assessment of symptoms
We conducted a questionnaire survey during the first wave (from February to April 2020) and the fourth wave of the COVID-19 pandemic (from March to April 2021). The questionnaire included the Geriatric Depression Scale (GDS-15) [10], Starkstein's Apathy scale [11], Parkinson's Fatigue scale [12], rapid eye movement (REM) sleep behavior disorder (RBD) screening questionnaire [13], and the Japanese version of the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) part 1 [14]. The disease stage was rated on the Hoehn-Yahr stage [15]. Validation study on the basis of a DSM–IV diagnosis for depression showed high discriminant validity of the GDS-15 with comparison of the Hamilton Depression Rating Scale (HDRS) as a screening to distinguish depressed from nondepressed patients in PD [16].
2.3. Statistical analysis
We present the median and interquartile range (IQR) for continuous variables. To compare the number of symptoms from the two periods, we used the paired t-test and Wilcoxon signed-rank test for continuous variables with normal distribution and those with skewed distribution, respectively. We conducted the McNemar test to compare the proportion of patients with GDS ≥ 6, Starkstein's Apathy scale ≥ 16, Parkinson's Fatigue scale ≥ 3.3, RBDSQ ≥ 5, and MDS-UPDRS part 1 ≥ 2. All reported p values are two-sided, and those < 0.05 were considered to be statistically significant. SPSS (version 24) was used for all the statistical analyses. We did not correct p values for multiple testing.
This study protocol was reviewed and approved by [Medical Ethics Committee of Nara Medical University], approval number [No. 2415]. The study has been granted an exemption from requiring written informed consent from Medical Ethics Committee of Nara Medical University, and we obtained the written informed consent of all patients.
3. Results
During the first wave in 2020, age (mean, IQR; 74 (71, 80) years) and disease duration (13.6 (9, 19.2) years) of 22 patients (men = 11) received levodopa (350 (287, 450) mg/day) in all and dopamine agonists in 11 patients (Table 1). The Hoehn-Yahr stage was significantly higher in the fourth COVID-19 wave (2.7 [2], [4]) than in the first wave (2.5 [2], [3], p = 0.025). The dose of dopaminergic medication was higher in nine patients in the fourth wave compared with the first wave.
Table 1.
Detailed clinical independent variables of 22 patients with Parkinson’s disease.
| Patient | age/sex | disease duration (yr) | early H-Y staging* | late H-Y staging** | wearing-off* | dyskinesia* | levodopa dosage* | dopamine agonist use = 1* | COMT inhibitor = 1* | MAO-B inhibitor = 1* | others PD medication* | PD medication increased = 1** |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 75/M | 25 | 5 | 5 | 1 | 0 | 600 | 1 | 0 | 1 | 1 | |
| 2 | 80/F | 5 | 2 | 2 | 0 | 0 | 100 | 0 | 0 | 1 | 0 | |
| 3 | 76/M | 6 | 2 | 2 | 1 | 1 | 350 | 0 | 0 | 1 | Acho, AMT | 1 |
| 4 | 73/M | 20 | 2 | 2 | 1 | 0 | 300 | 1 | 1 | 0 | 0 | |
| 5 | 79/F | 11 | 2 | 2 | 0 | 0 | 200 | 0 | 0 | 0 | 0 | |
| 6 | 82/M | 6 | 2 | 2 | 1 | 0 | 450 | 0 | 0 | 1 | 0 | |
| 7 | 64/F | 6 | 1 | 1 | 1 | 1 | 300 | 1 | 0 | 1 | 1 | |
| 8 | 62/F | 6 | 2 | 2 | 1 | 0 | 350 | 1 | 1 | 1 | 1 | |
| 9 | 78/F | 9 | 2 | 2 | 0 | 0 | 450 | 1 | 1 | 0 | 1 | |
| 10 | 71/F | 20 | 1 | 1 | 0 | 0 | 300 | 1 | 0 | 0 | AMT | 0 |
| 11 | 74/F | 5 | 3 | 4 | 0 | 0 | 300 | 1 | 1 | 0 | A2A | 1 |
| 12 | 62/F | 20 | 2 | 2 | 1 | 1 | 250 | 1 | 0 | 1 | Acho | 1 |
| 13 | 75/M | 15 | 2 | 3 | 0 | 0 | 400 | 0 | 0 | 1 | 0 | |
| 14 | 83/F | 24 | 5 | 5 | 1 | 1 | 600 | 0 | 0 | 0 | AMT, ZNS | 0 |
| 15 | 78/M | 5 | 2 | 3 | 1 | 0 | 200 | 0 | 0 | 0 | ZNS | 0 |
| 16 | 72/M | 6 | 3 | 3 | 1 | 0 | 200 | 1 | 0 | 0 | 1 | |
| 17 | 60/M | 11 | 3 | 3 | 1 | 1 | 600 | 1 | 1 | 0 | Acho, ZNS, A2A | 0 |
| 18 | 86/M | 7 | 4 | 4 | 1 | 0 | 300 | 0 | 0 | 1 | 0 | |
| 19 | 74/F | 9 | 2 | 2 | 1 | 0 | 300 | 1 | 0 | 0 | ZNS50 | 0 |
| 20 | 75/M | 6 | 4 | 5 | 1 | 0 | 450 | 0 | 1 | 0 | AMT, ZNS | 0 |
| 21 | 80/F | 9 | 3 | 4 | 1 | 0 | 400 | 0 | 0 | 0 | 1 | |
| 22 | 82/M | 4 | 2 | 2 | 0 | 0 | 300 | 0 | 0 | 1 | 0 |
HY: Hoehn Yahr stage, MAO-B: monoamine oxidase B, Acho: anticholinergic agent, AMT: amantadine, A2A: adenosine A2A receptor antagonist, ZNS: zonisamide.
*: when the first wave of COVID-19 epidemic, **: when the fourth wave of COVID-19 epidemic.
Compared with the first wave, the depression score was significantly higher in the fourth wave of the pandemic (median score of GDS: 4.00 vs. 5.50, p = 0.022). Consistently, the scores of symptoms on MDS-UPDRS part 1 in the fourth wave were significantly higher in hygiene (p = 0.033), handwriting (p = 0.033), performing hobbies and other activities (p = 0.035), and turning in bed (p = 0.046) than in the first wave (Table 2).
Table 2.
Difference of clinical variable between the first and fourth COVID-19 wave.
| 1st wave (n = 22) | 4th wave (n = 22) | p | |
|---|---|---|---|
| Depression, median (IQR) | 4.00 (1.75, 8.50) | 5.50 (2.75, 9.25) | 0.022 |
| Depression scale ≧6, n (%) | 9 (40.9) | 11 (50) | 0.625 |
| Apathy, median (IQR) | 15.00 (10.75, 19.25) | 15.00 (12.00, 19.50) | 0.329 |
| Apathy scale ≧16, n (%) | 11 (50) | 9 (40.9) | 0.219 |
| Fatigue, median (IQR) | 29.50 (18.00, 49.00) | 36.00 (22.25, 45.75) | 0.509 |
| Fatigue scale ≧3.3, n (%) | 3 (13.6) | 3 (13.6) | 1.000 |
| RBD, median (IQR) | 4.0 (3.0, 7.0) | 5.00 (3.00, 7.25) | 0.583 |
| RBD scale ≧5, n (%) | 10 (45.4) | 13 (59) | 0.453 |
| MDS-UPDRS part 1 Patient Questionnaire, median (IQR) | |||
| SLEEP PROBLEMS | 1.00 (1.00, 2.25) | 2.00 (1.00, 3.00) | 0.237 |
| DAYTIME SLEEPINESS | 2.00 (1.00, 2.00) | 2.00 (0.75, 3.00) | 0.763 |
| PAIN AND OTHER SENSATIONS | 1.00 (1.00, 2.25) | 2.00 (1.00, 2.00) | 0.206 |
| URINARY PROBLEMS | 1.50 (1.00, 2.25) | 1.00 (1.00, 3.00) | 0.644 |
| CONSTIPATION PROBLEMS | 2.00 (2.00, 3.00) | 2.00 (1.00, 3.00) | 0.49 |
| LIGHT HEADEDNESS ON STANDING | 1.00 (0.00, 1.25) | 1.00 (0.00, 2.00) | 0.968 |
| FATIGUE | 1.00 (0.00, 2.00) | 1.00 (0.00, 2.00) | 0.317 |
| SPEECH | 1.00 (0.00, 2.00) | 1.50 (0.00, 3.00) | 0.248 |
| SALIVA AND DROOLING | 1.00 (0.00, 3.00) | 2.00 (0.75, 3.00) | 0.154 |
| CHEWING AND SWALLOWING | 0.50 (0.00, 1.25) | 0.50 (0.00, 1.00) | 0.739 |
| EATING TASKS | 1.00 (0.00, 2.00) | 1.00 (0.75, 2.00) | 0.053 |
| DRESSING | 1.00 (0.75, 2.25) | 1.00 (1.00, 2.25) | 0.197 |
| HYGIENE | 1.00 (0.00, 2.00) | 1.00 (1.00, 2.00) | 0.033 |
| HANDWRITING | 1.00 (0.00, 2.00) | 1.50 (0.75, 2.00) | 0.033 |
| DOING HOBBIES AND OTHER ACTIVITIES | 1.00 (0.00, 2.00) | 1.00 (1.00, 3.00) | 0.035 |
| TURNING IN BED | 1.00 (0.75, 2.00) | 1.00 (1.00, 2.00) | 0.046 |
| TREMOR | 1.00 (1.00, 1.25) | 1.00 (0.00, 1.00) | 1.000 |
| GETTING OUT OF BED, A CAR, OR A DEEP CHAIR | 1.00 (1.00, 3.00) | 1.50 (1.00, 3.00) | 0.104 |
| WALKING AND BALANCE | 2.00 (1.00, 3.00) | 2.00 (1.00, 3.00) | 0.157 |
| FREEZING | 1.00 (0.00, 2.25) | 1.00 (0.00, 3.00) | 0.584 |
The number of GDS scores ≥ 6 in the first and fourth waves of the pandemic were 9 and 11, respectively. Wearing off and dyskinesia were evident in 15 and 5 patients, respectively, in the first wave. Patient 9, shown in Table 1, received antidepressants in both the first and fourth waves, and the other 21 patients did not receive antidepressants.
There was no significantly different factor between PD patients who became depressed defined ≥ 6 on GDS scores (n = 3) and those who did not become depressed during the COVID-19 pandemic. Between PD patients with worsened GDS scores (n = 13) and those whose GDS score was not deteriorated (n = 9), the score of daytime sleepiness on the MDS-UPDRS part 1 Patient Questionnaire differed in the first (median 2.09 and 1.2, respectively, p = 0.052) and fourth (median 2.3 and 0.67, respectively, p = 0.016) waves.
Basic demographic and clinical data between the enrolled 22 subjects and excluded 19 subjects when starting the second cohort of PHASE study showed a difference in age (68.0 ± 7.4 and 73.4 ± 6.7, respectively, p = 0.049) or the score for Mini Mental State Examination (28.8 ± 1.3 and 25.5 ± 3.8, respectively, p < 0.001), but other variables did not differ (Table 3). The UPDRS part 3 score at the beginning of the second cohort of the PHASE study was significantly lower in 3 patients who developed depression (mean, IQR; 8 (13, 6)) than in 19 patients who did not develop (mean, IQR; 23 (49, 5)) (p = 0.039), but the difference between patients with worsened GDS scores (n = 13; mean, IQR: 20 (47, 6)) and those whose GDS score had not worsened (n = 9; mean, IQR: 23 (49, 5)) was not statistically significant (p = 0.385). In terms of the UPDRS part 4 score, there was no difference between patients who developed depression and those who did not (p = 0.801) or between patients whose GDS scores worsened and those whose scores did not decrease (p = 0.232).
Table 3.
Basic clinical characteristics between the enrolled subjects and excluded subjects when starting the second cohort of PHASE study (Parkinson's disease and the relationships with circadian biological rhythms and sleep).
| total patients | enrolled 22 PD patients | excluded 19 PD patients | p | |
|---|---|---|---|---|
| age | 70.5 ± 7.5 | 68.0 ± 7.4 | 73.4 ± 6.7 | 0.049 |
| men | 20 | 11 | 9 | 1 |
| disease duration (months), median (IQR) | 51 (11, 262) | 54 (11, 241) | 50 (11, 262) | 0.548 |
| H-Y staging | 2.2 ± 1.1 | 2.0 ± 0.9 | 2.6 ± 1.1 | 0.051 |
| UPDRS part 1 item 2 (hallucination) | 9 | 3 | 6 | 0.26 |
| UPDRS part 3, median (IQR) | 18 (5, 86) | 16 (5, 49) | 21 (6, 86) | 0.44 |
| UPDRS part 4, median (IQR) | 0.7 (0, 24) | 0.9 (0, 14) | 0.5 (0, 24) | 0.326 |
| wearing-off * | 13 | 8 | 5 | 0.524 |
| dyskinesia* | 3 | 2 | 1 | 1 |
| Depression, median (IQR) | 5.9 (0, 14) | 5.00 (0, 14) | 6.67 (1, 14) | 0.16 |
| Depression scale ≧6, n (%) | 23 | 10 | 13 | 0.209 |
| Apathy, median (IQR) | 16.4 (5, 30) | 14.8 (5, 25) | 17.6 (10, 30) | 0.079 |
| Apathy scale ≧16, n (%) | 23 | 9 | 14 | 0.058 |
| Fatigue, median (IQR) | 33.5 (0, 63) | 31.5 (0, 63) | 35.3 (0, 59) | 0.979 |
| Fatigue scale ≧3.3, n (%) | 8 | 6 | 2 | 0.249 |
| RBD, median (IQR) | 4.1 (1, 13) | 4.5 (1, 10) | 3.5 (1, 13) | 0.469 |
| RBD scale ≧5, n (%) | 18 | 11 | 7 | 0.531 |
| MMSE | 27.3 ± 3.2 | 28.8 ± 1.3 | 25.5 ± 3.8 | <0.001 |
| PSQI | 6.2 ± 3.5 | 5.8 ± 3.4 | 6.7 ± 3.6 | 0.331 |
| medications | ||||
| levodopa dosage | 245.1 ± 143.5 | 213.6 ± 145.7 | 281.5 ± 135.6 | 0.075 |
| dopamine agonist use | 16 | 9 | 7 | 1 |
| COMT inhibitor use | 3 | 2 | 1 | 1 |
| MAO-B inhibitor use | 11 | 7 | 4 | 0.499 |
| history of depression | 4 | 3 | 1 | 0.607 |
| anti-depressant drug use | 4 | 2 | 2 | 1 |
HY: Hoehn Yahr stage, UPDRS: Unified Parkinson's disease Rating Scale, MMSE: Mini Mental State Examination, RBD: rapid eye movement (REM) sleep behavior disorder, * on URDRS part 4.
4. Discussion
The present study suggested that the number of depressive symptoms determined by the same depression scale tended to be higher in the fourth wave compared with the first wave of the pandemic in Japan. There are only limited data available from previous longitudinal studies. One study showed that depressed mood worsened in 31.6 % of patients during the COVID-19 pandemic based on the comparison of different questionnaires a month before the pandemic started [2]. The event scale assessed by a psychological instrument during the lockdown period was associated with a higher Beck Depression Inventory (BDI) score [4]. Pre-lockdown BDI scores were significantly correlated with depression, anxiety, and stress Scale-21 (DASS) depression during the lockdown period [5]. These studies obtained psychological symptoms only once before or after the lockdown. Only one study evaluated psychological distress from two time points during the COVID-19 pandemic [3]. Among patients with advanced PD, the prevalence of depression during the lockdown (39 %) decreased to 34.1 % at the end of the lockdown. However, the reduction was not significant [3].
Our findings are consistent with the results of the previous studies that psychological symptoms had worsen after the COVID-19 waves. Patients with PD may have become anxious and, in some cases, prone to depression during the COVID-19 pandemic because of inaccessibility or interruptions to their family hospital, fear of SARS-CoV-2 infection, PD complications related to COVID-19, and interruption of non-pharmacological treatments [1], [2], [3]. Thirty-five percent of patients worried about the interruption of physiotherapy, psychological support, or cognitive stimulation, and 48 % felt the possible worsening of PD symptoms after the limitation of outdoor physical activity [3]. This aspect was reported by a cross-sectional study using data obtained via telephone interviews about the psychological symptoms before and after COVID-19 waves [17]. Depression reduces the frequency of going out and leisure activities, and diminishes motivation to improve daily life. This impairs motor abilities and accompanying non-motor symptoms [18]. Our study also showed that the number of hobbies and other activities was lower at the end of the fourth COVID-19 wave. The psychological impact during the COVID-19 pandemic was significantly associated with treatment-related motor complications [4]. Hygiene, handwriting, and turning in bed deteriorated parallel to the decrease in the BDI score.
The Hoehn-Yahr stage increased slightly. Depression is a risk factor for PD progression [19]. Interaction between motor and non-motor symptoms can create a vicious cycle in patients with PD and may affect their quality of life. Since the COVID-19 pandemic is becoming protracted due to the appearance of mutant strains, it is important to know the change in the severity of depression during the phases of the COVID-19 pandemic.
In the non-PD population, GDS scores of 5–9 were considered mild depression. However, a validation study of the depression screening questions recommended by the UK National Institute for Health and Clinical Excellence (NICE) in PD patients attending a hospital outpatient PD clinic demonstrated that the optimal cut-off of the GDS-15 for the identification of major depression on DSM-IV diagnostic criteria was 5/6, which gave a sensitivity of 86% and specificity of 86%, while the specificity of the cut-off 8/9 was 95% [20]. In addition, if the GDS score exceeds the cutoff value of 5, it corresponds to major depression in the DSM-IV; thus, it seems difficult to consider that the depression is mild, even with a rise of only two points. Longitudinal evolution of non-motor symptoms using Parkinson's Progression Markers Initiative data showed that young-onset PD compared to middle- and late-onset PD had more progression in depression by a significant increases of 0.32 points on the GDS-15 [21].
We did not measure MDS-UPDRS Part 3. One reason for this was that patients were unable to visit hospitals because of restrictions on going out or fear of COVID-19 infection during the COVID-19 pandemic. Song et al. showed worsening of both motor and non-motor PD symptoms after a follow-up of 4.6 months during the COVID-19 pandemic, especially in slowness, tremors, feeling stress, fatigue, and pain [22]. Similar to Japan, the Korean government placed social distancing, staying at home, and refraining from going out as much as possible. However, the UPDRS Part 3 score did not show a significant difference during the COVID-19 pandemic. Moreover, both the GDS score and the Hoehn-Yahr stage worsened in the present study. Further longitudinal studies are needed to determine whether UPDRS changes can lead to worsening of depression.
The present study had several limitations. Sample size is small, and all participants were from a single hospital in a local place, which may limit the generalizability of our findings. We did not evaluate the symptoms of anxiety, which have been reported to increase during the COVID-19 pandemic. An increase in anxiety may be a mediating factor in depressive symptoms. The GDS-15 distinguish patients with PD with and without depression as a screening instrument [16]. One validation study on PD suggests that the GDS and its subscales appear to primarily measure anxiety, apathy, and fatigue, which may be predominant in PD-depression [23]. Second, depressive symptoms could develop in the normal population during the COVID-19 pandemic; however, the normal control group was not enrolled in the present study. Patients with PD experience more depression during the COVID-19 pandemic than the normal population [24]. Finally, we did not adjust the p-values for the following reasons. First, this research was not confirmative but exploratory [25]. Second, precisely adjusting the p-value is difficult because the outcomes are related [26]. However, we should pay attention to the type 1 error due to repeated testing, and further study based on adequate statistical power with a large sample size is needed.
In conclusion, our observation over a year between the early and later phases of the COVID-19 pandemic showed an increase in the severity of depression in patients with PD. This was consistent with the previous knowledge that depressive symptoms among patients with PD developed within two months before and after the lockdown [5].
5. Ethical approval and consent to participation
This study protocol was reviewed and approved by [Medical Ethics Committee of Nara Medical University], approval number [No. 2415]. The study has been granted an exemption from requiring written informed consent from Medical Ethics Committee of Nara Medical University, and we obtained the written informed consent of all patients. The appropriate participants' informed consent in compliance with the Helsinki Declaration was obtained. No investigations or interventions were performed outside routine clinical care. As this is without experimental intervention into routine care. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
6. Availability of data and material
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Funding
This work was supported by research funding from JSPS KAKENHI (grant numbers: 15 K09356 and 22 K07496), and Mitsui Sumitomo Insurance Welfare Foundation research grand.
8. Competing interest
Drs. Obayashi and 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. The other authors reported no conflict of interest.
9. Authors’ contribution
-
1)
Research project: Hiroshi Kataoka, Kenji Obayashi, Keigo Saeki;
-
2)
Statistical analysis: Hiroshi Kataoka, Keigo Saeki;
-
3)
Writing of the first draft: Hiroshi Kataoka, Keigo Saeki;
-
4)
Review and Critique: Hiroshi Kataoka, Kenji Obayashi, Yoshiaki Tai, Kazuma Sugie, Keigo Saeki.
10. Consent to publication
All authors agreed with consent of publication of our manuscript. We obtained informed consent from the participants in order to publish their identity revealing information.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
We would like to thank Naomi Takenaka, Sachiko Sogahara, and Keiko Nakajima for their valuable help with data collection and analysis.
References
- 1.Weintraub D., Mamikonyan E. The neuropsychiatry of Parkinson disease: a perfect storm. Am. J. Geriatr. Psychiatry. 2019;27(9):998–1018. doi: 10.1016/j.jagp.2019.03.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.van der Heide A., Meinders M.J., Bloem B.R., Helmich R.C. The Impact of the COVID-19 Pandemic on Psychological Distress, Physical Activity, and Symptom Severity in Parkinson's Disease. J. Parkinsons Dis. 2020;10(4):1355–1364. doi: 10.3233/JPD-202251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Montanaro E., Artusi C.A., Rosano C., Boschetto C., Imbalzano G., Romagnolo A., Bozzali M., Rizzone M.G., Zibetti M., Lopiano L. Anxiety, depression, and worries in advanced Parkinson disease during COVID-19 pandemic. Neurol. Sci. 2021;4:1–8. doi: 10.1007/s10072-021-05286-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.De Micco R., Siciliano M., Sant'Elia V., Giordano A., Russo A., Tedeschi G., Tessitore A. Correlates of Psychological Distress in Patients with Parkinson's Disease During the COVID-19 Outbreak. Mov. Disord. Clin. Pract. 2021;8(1):60–68. doi: 10.1002/mdc3.13108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Shalash A., Roushdy T., Essam M., Fathy M., Dawood N.L., Abushady E.M., Elrassas H., Helmi A., Hamid E. Mental Health, Physical Activity, and Quality of Life in Parkinson's Disease During COVID-19 Pandemic. Mov. Disord. 2020;35:1097–1099. doi: 10.1002/mds.28134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Hughes A.J., Daniel S.E., Kilford L., Lees A.J. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry. 1992;55(3):181–184. doi: 10.1136/jnnp.55.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Gilman S., Wenning G.K., Low P.A., Brooks D.J., Mathias C.J., Trojanowski J.Q., Wood N.W., Colosimo C., Durr A., Fowler C.J., Kaufmann H., Klockgether T., Lees A., Poewe W., Quinn N., Revesz T., Robertson D., Sandroni P., Seppi K., Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670–676. doi: 10.1212/01.wnl.0000324625.00404.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Litvan I., Agid Y., Calne D., Campbell G., Dubois B., Duvoisin R.C., Goetz C.G., Golbe L.I., Grafman J., Growdon J.H., Hallett M., Jankovic J., Quinn N.P., Tolosa E., Zee D.S. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996;47(1):1–9. doi: 10.1212/wnl.47.1.1. [DOI] [PubMed] [Google Scholar]
- 9.McKeith I.G. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J. Alzheimers Dis. 2006;9(s3):417–423. doi: 10.3233/jad-2006-9s347. [DOI] [PubMed] [Google Scholar]
- 10.Leentjens A.F.G., Verhey F.R.J., Luijckx G.-J., Troost J. The validity of the Beck depression inventory as a screening and diagnostic instrument for depression in patients with Parkinson's disease. Mov. Disord. 2000;15(6):1221–1224. doi: 10.1002/1531-8257(200011)15:6<1221::aid-mds1024>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
- 11.Starkstein S.E., Merello M., Jorge R., Brockman S., Bruce D., Power B. The syndromal validity and nosological position of apathy in Parkinson's disease. Mov. Disord. 2009;24(8):1211–1216. doi: 10.1002/mds.22577. [DOI] [PubMed] [Google Scholar]
- 12.Brown R.G., Dittner A., Findley L., Wessely S.C. The Parkinson fatigue scale. Parkinsonism Relat. Disord. 2005;11(1):49–55. doi: 10.1016/j.parkreldis.2004.07.007. [DOI] [PubMed] [Google Scholar]
- 13.Miyamoto T., Miyamoto M., Iwanami M., Kobayashi M., Nakamura M., Inoue Y., Ando C., Hirata K. The REM sleep behavior disorder screening questionnaire: validation study of a Japanese version. Sleep Med. 2009;2009(10):1151–1154. doi: 10.1016/j.sleep.2009.05.007. [DOI] [PubMed] [Google Scholar]
- 14.Goetz C.G., Tilley B.C., Shaftman S.R., Stebbins G.T., Fahn S., Martinez-Martin P., Poewe W., Sampaio C., Stern M.B., Dodel R., Dubois B., Holloway R., Jankovic J., Kulisevsky J., Lang A.E., Lees A., Leurgans S., LeWitt P.A., Nyenhuis D., Olanow C.W., Rascol O., Schrag A., Teresi J.A., van Hilten J.J., LaPelle N. Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society UPDRS Revision Task Force: Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov. Disord. 2008;23(15):2129–2170. doi: 10.1002/mds.22340. [DOI] [PubMed] [Google Scholar]
- 15.Hoehn M.M., Yahr M.D. Parkinsonism: onset, progression and mortality. Neurology. 1967;17(5) doi: 10.1212/wnl.17.5.427. [DOI] [PubMed] [Google Scholar]
- 16.Weintraub D., Oehlberg K.A., Katz I.R., Stern M.B. Test characteristics of the 15-item geriatric depression scale and Hamilton depression rating scale in Parkinson disease. Am. J. Geriatr. Psychiatry. 2006;14(2):169–175. doi: 10.1097/01.JGP.0000192488.66049.4b. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Brown E.G., Chahine L.M., Goldman S.M., Korell M., Mann E., Kinel D.R., Arnedo V., Marek K.L., Tanner C.M. The Effect of the COVID-19 Pandemic on People with Parkinson's Disease. J. Parkinsons Dis. 2020;10(4):1365–1377. doi: 10.3233/JPD-202249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Oppo V., Serra G., Fenu G., Murgia D., Ricciardi L., Melis M., Morgante F., Cossu G. Parkinson’s disease symptoms have a distinct impact on caregivers’ and patients’ stress: a study assessing the consequences of the COVID-19 lockdown. Mov. Disord. Clin. Pract. 2020;7:865–867. doi: 10.1002/mdc3.13030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Burn D.J. Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease. Mov. Disord. 2002;17(3):445–454. doi: 10.1002/mds.10114. [DOI] [PubMed] [Google Scholar]
- 20.Baillon S., Dennis M., Lo N., Lindesay J. Screening for depression in Parkinson's disease: the performance of two screening questions. Age Ageing. 2014;43(2):200–205. doi: 10.1093/ageing/aft152. [DOI] [PubMed] [Google Scholar]
- 21.Kim R., Shin J.H., Park S., Kim H.-J., Jeon B. Longitudinal evolution of non-motor symptoms according to age at onset in early Parkinson's disease. J. Neurol. Sci. 2020;418 doi: 10.1016/j.jns.2020.117157. [DOI] [PubMed] [Google Scholar]
- 22.Song J., Ahn J.H., Choi I., Mun J.K., Cho J.W., Youn J. The changes of exercise pattern and clinical symptoms in patients with Parkinson's disease in the era of COVID-19 pandemic. Parkinsonism Relat. Disord. 2020;80:148–151. doi: 10.1016/j.parkreldis.2020.09.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lopez F.V., Split M., Filoteo J.V., Litvan I., Moore R.C., Pirogovsky-Turk E., Liu L., Lessig S., Schiehser D.M. Does the Geriatric Depression Scale measure depression in Parkinson's disease? Int. J. Geriatr. Psychiatry. 2018;33(12):1662–1670. doi: 10.1002/gps.4970. [DOI] [PubMed] [Google Scholar]
- 24.Shalash A., Roushdy T., Essam M., Fathy M., Dawood N.L., Abushady E.M., Elrassas H., Helmi A., Hamid E. Mental health, physical activity, and quality of life in Parkinson’s disease during COVID-19 pandemic. Mov. Disord. 2020;35:1097–1099. doi: 10.1002/mds.28134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Rothman K.J. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1(1):43–46. [PubMed] [Google Scholar]
- 26.Althouse A.D. Adjust for Multiple Comparisons? It's Not That Simple. Ann. Thorac. Surg. 2016;101(5):1644–1645. doi: 10.1016/j.athoracsur.2015.11.024. [DOI] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.