Effect of COVID-19 Related Lockdown on Nonmotor Symptoms of Parkinson's Disease.

Sir,

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a worldwide crisis. To limit the spread of the disease, social distancing has been advocated strongly, and several countries including India have imposed lockdown with suspension of daily outdoor activities. This lockdown situation would appear to be especially difficult for Parkinson's disease (PD) patients to cope with. It is challenging for the PD patients to adjust to these changes owing to their cognitive and motor inflexibility.[1] There is an increase in anxiety and stress, as well as worsening of motor symptoms.[2] Another important concern was the reduced access to health services and procurement of medications during the lockdown,[2] which could aggravate both motor and nonmotor symptoms (NMS) in PD. We undertook this study to evaluate the changes of NMS of PD patients during the COVID-19 lockdown situation.

This study recruited PD patients under regular follow-up at the Movement Disorders clinic of Bangur Institute of Neurosciences, Kolkata, India, who were enrolled in an ongoing study approved by the institutional ethics committee. According to institute protocol, we contacted the patients/caregivers over telephone for routine follow-up. We included patients who had visited our institute at least once during the 3 months preceding the beginning of lockdown, and were on a stable dosing of anti-Parkinsonian medications not requiring any change on their last visit. We compared this baseline data with that obtained from our telephonic interview (done in May–June 2020). We collected demographic details, enquired regarding COVID-19 and difficulties faced during the lockdown, and asked about any change in the motor and nonmotor symptoms of PD. For NMS, we used the 30-item NMS Questionnaire (NMSQuest),[3] and additionally enquired for fatigue. Duration of disease was noted and the pre-lockdown modified Hoehn and Yahr (HY) staging was utilized.

Out of total 55 patients, 78.2% were male. Every responder had some knowledge about COVID-19. 52.7% had an overall perception of deterioration during lockdown, and 9.1% said that their condition improved. None of the patients had COVID-19 or a known history of close contact with a patient of COVID-19. All the patients were continuing their medications, although, 10.9% had some difficulty procuring medicines in the initial stages of lockdown. Patients reported deterioration of motor symptoms such as an increase in slowness (41.8%), stiffness (25.5%), or tremor (30.9%). There was significant increase in prevalence of total NMS per patient (P = <0.001), as well as several individual NMS such as, anxiety, impaired concentration, loss of interest, weight loss, and pain [Table 1]. Other NMS also showed increased prevalence during lockdown except, vomiting, bowel incontinence, hyposmia, sexual problems, double vision, and delusion. NMS which were already present pre-lockdown, showed an increase in severity except double vision and bowel incontinence. Taking together the appearance of new symptoms and increase in severity of pre-existing symptoms, the NMS could be grouped as follows- ≥40% increase- impaired concentration, weight loss, anxiety, loss of interest, fatigue, and pain; 20–39% increase- depression, daytime somnolence, restless legs, forgetfulness, constipation, insomnia, dizziness, and urinary urgency; <20% increase- rest of the NMS. Younger patients experienced greater overall worsening of NMS (r s= -0.293, P = 0.03), and of loss of interest in particular (P = 0.003). Worsening of impaired concentration was associated with longer duration of disease (P = 0.025). There was no significant difference in increase of NMS regarding gender and HY staging of the patients. There was also no association between worsening of the motor symptoms and increase in NMS.

Table 1

Increase of Nonmotor Symptoms during Lockdown

Part A Individual Nonmotor Symptoms#
NMS	Frequency of NMS			Increase of NMS during lockdown
	Pre-lockdown (N)	Post-lockdown (N)	P	n (%)	P
					Age	Sex	HY	Duration
Impaired concentration	32	43	0.024*	27 (49.1)	0.051	0.469	0.466	0.025*
Weight loss	38	47	0.041*	25 (45.5)	0.283	0.721	0.204	0.435
Anxiety	35	46	0.017*	23 (41.8)	0.398	0.990	0.417	0.350
Loss of interest	25	37	0.021*	23 (41.8)	0.003*	0.190	0.643	0.554
Fatigue	47	50	0.376	22 (40)	0.449	0.143	0.252	0.856
Unexplained pain	21	36	0.004*	22 (40)	0.169	0.424	0.055	0.309
Depression	34	41	0.152	20 (36.4)	0.096	0.267	0.598	0.150
Daytime somnolence	35	42	0.145	20 (36.4)	0.234	0.355	0.132	0.264
Restless legs	40	47	0.101	20 (36.4)	0.096	0.355	0.708	0.232
Forgetfulness	33	38	0.319	16 (29.1)	0.303	0.714	0.739	0.268
Constipation	37	41	0.401	15 (27.3)	0.307	0.594	0.253	0.494
Insomnia	25	33	0.127	14 (25.5)	0.985	0.429	0.651	0.194
Dizziness	23	31	0.127	14 (25.5)	0.816	0.429	0.713	0.184
Urinary urgency	32	37	0.324	12 (21.8)	0.071	0.275	0.751	0.532
Part B Total Nonmotor Symptoms Per Patient
Total NMS per patient	Frequency of total NMS		P	Increase of total NMS during lockdown
	Pre-lockdown (Mean±SD)	Post-lockdown (Mean±SD)		Mean±SD	P
					Age	Sex	HY	Duration
	13.04±3.89	15.55±3.18	<0.001*	6.6±3.30	0.03*	0.402	0.857	0.523

*Significance level at P<0.05, #Showing NMS with ≥20% increase during lockdown

52.7% of patients deteriorated during lockdown. An Indian study has documented worsening in 28% of PD patients,[2] whereas a Spanish study reported deterioration in 65.7% patients.[4] The limitations imposed by lockdown including social isolation, restriction of physical activity, and sudden change in lifestyle, along with the anxiety and uncertainty regarding COVID-19, contribute to the aggravation of symptoms in PD patients.[1] A study showed that worsening of PD patients was dependent on the reduction of physical activity during lockdown.[5] 15 NMS showed ≥20% increase, and none of the NMS had an overall decrement. Previous studies have described an increase in some of these NMS during the COVID-19 pandemic, such as anxiety, stress, depression, and cognitive impairment.[678] However, in addition to these symptoms, our study documented change in the wide spectrum of NMS. Other studies from around the world have also showed worsening of NMS [Table 2]. A Turkish study found maximum worsening in orthostatic hypotension,[9] whereas an Indian multicenter study reported the highest increase in easy fatiguability followed by sleep disturbances.[10] An Italian report showed worsening of anxiety, mood, and sleep,[11] and an American study also documented significant involvement of these NMS domains along with autonomic and cognitive impairment.[12] We found comparable worsening of these symptoms; however, the greatest increase was for impaired concentration, weight loss, anxiety, and loss of interest. Hence, although there were some differences regarding the magnitude of worsening of the various NMS, there was a similar trend in most of these studies.

Table 2

Frequencies of increase in nonmotor and motor symptoms in patients of Parkinson’s disease and comparison with other studies

Present study n=55		Turkey[9] n=86		Nine centers of India[10] n=832		Tuscany, Italy[11]n=740		USA[12] n=5429 (people with PD)
Nonmotor
Impaired concentration	27 (49.1)	Orthostatic hypotension	26 (30.2)	Easy fatiguability	209 (25.1)	Anxiety	183 (25.0)	Mood	36.5%
Weight loss	25 (45.5)	Fatigue	21 (24.4)	Sleep disturbances	199 (23.9)	Mood	181 (24.7)	Sleep	36.5%
Anxiety	23 (41.8)	Pain	18 (20.9)	Pain	181 (21.8)	Insomnia	163 (22.2)	Autonomic	20.6%
Loss of interest	23 (41.8)	Daytime sleepiness	18 (20.9)	Anxiety	179 (21.5)			Cognitive	18.5%
Fatigue	22 (40)	Anxiety	13 (15.1)	Depressive symptoms	168 (20.2)
Unexplained pain	22 (40)	Cognitive impairment	12 (14)	Constipation	163 (19.6)
Depression	20 (36.4)	Constipation	9 (10.5)	Forgetfulness	149 (17.9)
Daytime somnolence	20 (36.4)	Apathy	7 (8.1)	Urinary problems	111 (13.3)
Restless legs	20 (36.4)	Urinary disorder	5 (5.8)	Postural dizziness	108 (12.9)
Forgetfulness	16 (29.1)	Hallucination	5 (5.8)	Aggressive or impulsive behavior	96 (11.5)
Constipation	15 (27.3)	Sleep disorder	4 (4.7)	Obsessive thoughts	79 (9.5)
Insomnia	14 (25.5)	Depression	2 (2.3)	Visual hallucinations	50 (6.01)
Dizziness	14 (25.5)	Dopamine dysregulation syndrome	1 (1.2)	Auditory hallucinations	35 (4.2)
Urinary urgency	12 (21.8)
Motor
Slowness	23 (41.8)	Bradykinesia	40 (46.5)	Slowness	259 (31.1)	Motor	217 (29.6)	Motor	47.2%
Tremor	17 (30.9)	Tremor	18 (20.9)	Tremor	173 (20.8)
Stiffness	14 (25.5)	Postural instability	19 (22.1)	Stiffness	203 (24.4)

*Numbers in parentheses are percentage

Worsening of NMS was greater in younger patients. The younger patients were likely to be more active prior to the lockdown and probably engaged in jobs which were restricted because of the lockdown. This might lead to an increase in NMS, especially anxiety and depression, and explain the loss of interest. Impaired concentration, loss of interest, and forgetfulness might be linked to increased depression and anxiety, although, disruption of daily routine and difficulty of coping with the sudden change of lifestyle may cause cognitive stress that exacerbates or unmasks cognitive impairment. Lack of regular exercise and physical activity possibly aggravated pain and fatigue. However, fatigue may be a manifestation of viral infections including COVID-19, although none of them tested positive for COVID-19 in our study. None of our patients developed new onset hyposmia, and both patients with increased severity of pre-existing hyposmia had tested negative for COVID-19.

To conclude, this study documented worsening of motor and several nonmotor symptoms in PD patients during the COVID-19 pandemic related lockdown in India.

Financial support and sponsorship

This work was supported by Indian Council for Medical Research under Grant No. BMS/TF/TRANS-NEURO/2014-3454/SEP-15/36/WB/GOVT.

Conflicts of interest

There are no conflicts of interest.