Highlights
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• 6% of Parkinson’s Disease (PD) patients did not develop any non-motor symptoms (NMS) despite the long duration of the illness.
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• REM sleep behaviour disorder (63%) was the most frequent NMS overall, followed by constipation (59%) and urinary dysfunction (55%).
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• Pre-motor onset of NMS was present in 24% of patients, whereas post-motor onset was seen in 70%.
Introduction
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the hallmark of nigrostriatal dopaminergic dysfunction. The accumulation of misfolded intracellular aggregates of alpha-synuclein (Lewy bodies) in the central nervous system and peripheral nervous system plays an essential role in the pathogenesis of neurodegeneration. According to the alpha-Synuclein Origin site and Connectome model Reference Borghammer1,Reference Horsager and Borghammer2 the accumulation of alpha-synuclein in the nigrostriatal pathway and the cerebral hemisphere gives rise to motor symptoms such as tremor, rigidity, bradykinesia and gait dysfunction. The occurrence of non-motor symptoms (NMS) such as rapid eye movement sleep behaviour disorder (RBD), constipation, hyposmia and urinary dysfunction is ascribed to the deposition of alpha-synuclein in the brainstem, sympathetic trunk and the enteric and autonomic nervous systems.
RBD is one of the most common NMS in PD, and its prevalence ranges from 20% to 72%. Reference Kim and Jeon3 Constipation is one of the primary and disabling NMS in PD, with a prevalence ranging from 24.6% to 63%, and has been shown to predate motor symptoms by many years. Reference Stocchi and Torti4 The prevalence of hyposmia ranges from 64% to 90% in PD and predates the motor symptoms by at least 4 years. Reference Xiao, Chen and Le5 Lower urinary tract symptoms, including urinary urgency, incontinence and retention, were also a common non-motor manifestation and were present in up to 61% of the patients. Reference Li, Cui, Yan, Cao and Feng6
There are a paucity of data regarding the evolution of NMS in patients with long-standing PD. This is one of the first studies documenting the evolution of NMS in patients with long-standing PD (10 or more years disease duration). In this study, we looked at the prevalence and the trajectory of the following NMS: RBD, constipation, hyposmia, urinary dysfunction, psychosis, mood disorders (depression, anxiety), orthostatic hypotension and impulse control disorders (ICDs) in the pre-motor stage and after the development of motor symptoms of PD for at least 10 years.
Methodology
This was a single-centre, cross-sectional study conducted in the Department of Neurology, National Institute of Mental Health and Neurosciences from May 2023 to December 2024. The study was approved by the institute’s ethics committee (NIMH/DO/IEC/[BS & NS DIV]/2022), and informed consent was obtained from the patients or their caregivers. A total of 100 subjects were recruited for the study. The inclusion criteria for study subjects were consecutive patients with clinically diagnosed idiopathic PD aged 18 years or older, of either gender, who met the United Kingdom Parkinson’s Disease Society Brain Bank criteria with a minimum disease duration of 10 years. The 10-year cutoff was selected to include patients with advanced disease, in which the disease had progressed sufficiently to exhibit NMS. Exclusion criteria were patients with atypical parkinsonism, drug-induced or secondary parkinsonism and patients with significant organ dysfunction.
Demographic details of the patients were collected, and a thorough clinical assessment was performed with special emphasis on the motor and non-motor manifestations of PD. Motor manifestations included symptoms related to rigidity, tremors, bradykinesia or hypokinesia, hypophonia, postural instability, gait disturbances and medication-related symptoms such as peak-dose dyskinesias. The details regarding the onset of NMS, including RBD, hyposmia, symptoms of autonomic dysfunction such as constipation, urinary urgency or incontinence, orthostatic hypotension, symptoms related to cognitive dysfunction, mood disturbances such as depression or anxiety, ICDs, delusions and hallucinations, were collected from the patient and the caregivers based on their history or by prior medical records if available. Accurate temporal profiling and mapping of the evolution timeline were done as much as possible for each patient’s motor and non-motor symptoms. History was obtained from both patients and caregivers.
The patients were also assessed for the severity of motor symptoms and NMS using various non-motor scales and questionnaires after obtaining the necessary permission from the sources. The severity of motor symptoms was assessed using the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and the modified Hoehn and Yahr (H&Y) staging. The severity of NMS at the time of recruitment was assessed only for symptoms that had occurred within the month prior to the interview. The following non-motor scales and questionnaires were used: Parkinson’s Disease Nonmotor Symptoms Questionnaire (PD-NMSQ), Montreal Cognitive Assessment (MoCA) scale, Pittsburgh Sleep Quality Index, RBD Screening Questionnaire (RBDSQ), Questionnaire for Impulse and Compulsive Disorders in Parkinson’s disease – Rating Scale (QUIP-RS) and Restless Leg Syndrome Rating Scale (RLS-RS). The questionnaire was completed by patients and their caregivers to address the issue of cognitive impairment, which can affect the reliability of NMS severity assessments. The caregiver who had been staying with the patient in the preceding month was the only one allowed to respond to the questionnaire. At the time of data collection, the patients were on a stable dose of medications unchanged for at least 3 months. All the data were incorporated into a Microsoft Excel sheet, and the descriptive data were tabulated. Continuous variables were expressed by mean ± standard deviation and range, and categorical variables were expressed as frequencies, percentages and ratios.
Results
Clinical and demographic details
The data analysis was performed on 100 patients in the study. In our study, 68% of the participants were males, and 32% were females. The mean age at assessment was 58.8 ± 9.7 years, with an age range of 31–82 years. The age group with the highest number of patients in this study was 61–70 years (43%), followed by the 51–60 years age group (33%). The mean age at onset of motor symptoms was 45.7 ± 10.1 years (range: 17–67 years). The majority of our patients had the onset of motor symptoms of PD in the 41–50 years age group (45%), followed by the 51–60 years age group (27%). Seventy percent had the age of onset before 50 years (early-onset PD), and 30% had the age of onset after 50 years (late-onset PD). The mean disease duration was 13.1 ± 3.3 years (range: 10–26 years), with 80% of patients having a disease duration of 10–15 years, 15% having a disease duration of 1–20 years and 5% having a disease duration of 21–30 years.
Motor symptoms
The profile of motor symptoms showed that bradykinesia was the most common motor symptom (100%), followed by tremor (82%), hypophonia (74%), freezing of gait (57%) and postural instability (51%). Medication-related motor fluctuations, including peak-dose dyskinesias (86%) and the wearing-off phenomenon (80%), were also present. With relation to the severity of motor symptoms, the mean MDS-UPDRS part III off-state score was 49.6 ± 19.1, and the on-state score was 18.6 ± 13.7. The mean modified H&Y staging score was 2.6 ± 0.9. Regarding the motor subtypes, 40% had tremor-dominant, 54% had akinetic-rigid and 6% had indeterminate subtypes of PD.
Non-motor symptoms
The prevalence of NMS indicated that 94% of individuals had experienced at least one NMS episode during the assessment period. Six percent of the patients did not experience any NMS at the time of assessment, despite having a disease duration of more than 10 years. RBD was the most prevalent NMS, seen in 63% of the patients, followed by constipation (59%), urinary dysfunction (55%), hyposmia (31%), psychotic symptoms such as delusions or hallucinations (26%), depression (25%), ICDs (18%) and orthostatic hypotension (10%) (Figure 1). The overall burden and severity of NMS were assessed using the PD-NMSQ (score range 0–30). Seventy-five percent had a PD-NMSQ score of greater than 7, which was suggestive of a significant burden of NMS. With relation to the number of NMS, 16% had a single NMS, 19% had two NMS, 21% had three NMS and 39% had more than three NMS. Further details on the demographic, motor and non-motor characteristics of the cohort are given in Table 1.
Prevalence of various non-motor symptoms at the time of presentation. ICD = impulse control disorders; OH = orthostatic hypotension; RBD = rapid eye movement sleep behaviour disorder.
Demographic, motor and non-motor characteristics of the cohort (n = 100)
ICD = impulse control disorders; MDS-UPDRS = Movement Disorder Society – Unified Parkinson”s Disease Rating Scale; PD = Parkinson”s disease; RBD = rapid eye movement sleep behaviour disorder.
Rapid eye movement sleep behavioural disorder
The prevalence of RBD was 63% in our study. Pre-motor onset of RBD was seen in 8%, of which 4% had the onset of RBD within 5 years, 3% had between 5 and 10 years and 1% had more than 10 years before the onset of the first motor symptom. The mean duration of onset of pre-motor RBD was −9.1 ± 7.9 years (considering 0 as the point of motor symptom onset). Post-motor onset of RBD was observed in 55% of cases, with 15% developing RBD within 5 years, 27% between 5 and 10 years and 13% more than 10 years after motor symptom onset. The mean duration of onset of post-motor RBD was 5.8 ± 6.9 years. The RBDSQ was used to assess RBD severity. The mean RBDSQ score was 4.6 ± 2.7 (range: 0–13). Fifty-five percent had the RBDSQ score ≥ 5/13, which is the cutoff suggestive of the presence of RBD.
Constipation
The prevalence of constipation was 59%. Pre-motor onset of constipation was observed in 8%, with 5% experiencing onset within 5 years and 3% between 5 and 10 years prior to motor symptom onset. The mean duration of onset of pre-motor constipation was –4.5 ± 3.8 years. Post-motor onset of constipation was observed in 51% of cases, with 12% developing constipation within 5 years, 31% between 5 and 10 years and 8% more than 10 years after motor symptom onset. The mean duration of onset of post-motor constipation was 6.1 ± 5.0 years.
Hyposmia
Hyposmia was assessed historically but not specifically tested using any smell test. The prevalence of hyposmia was 31%, with pre-motor onset of hyposmia observed in 3%. The mean duration of onset of pre-motor hyposmia was –4.0 ± 1.7 years. Post-motor onset of hyposmia was observed in 28% of cases, with 10% developing hyposmia within 5 years, 12% between 5 and 10 years and 6% more than 10 years after motor symptom onset. The mean duration of onset of post-motor hyposmia was 6.4 ± 4.7 years.
Urinary dysfunction
The prevalence of urinary dysfunction was 55%, with pre-motor onset observed in 1%. Post-motor onset of urinary dysfunction was observed in 54% of cases, with 2% developing it within 5 years, 36% developing it between 5 and 10 years and 16% developing it more than 10 years after motor symptom onset. The mean duration of onset of post-motor urinary dysfunction was 9.4 ± 3.5 years.
Orthostatic hypotension
The prevalence of symptoms suggestive of orthostatic hypotension was 10%, which occurred after motor symptom onset in all those with it. Seven percent developed it between 5 and 10 years, and 3% developed it more than 10 years after motor symptom onset. The mean duration of onset of post-motor orthostatic hypotension was 10.0 ± 4.7 years.
Psychosis
The prevalence of psychotic symptoms, including delusions and hallucinations, was 26%, of which 1% had pre-motor onset. Post-motor onset of psychotic symptoms was seen in 25%, of which 1% developed it within 5 years, 20% developed it between 5 and 10 years and 5% developed it more than 10 years after motor symptom onset. The mean duration of onset of post-motor psychotic symptoms was 8.1 ± 2.1 years. Ten percent had medication-related psychotic symptoms due to dopamine agonists or anticholinergic intake.
Impulse control disorders
The prevalence of ICDs was 18%, all of which developed after the onset of motor symptoms. One percent developed ICDs within 5 years, 11% developed between 5 and 10 years and 6% developed ICDs more than 10 years after motor symptom onset. The mean duration of onset of post-motor ICDs was 9.2 ± 5.6 years. The QUIP-RS was used to assess the severity of ICDs. Four ICDs (compulsive gambling, eating, buying and hypersexual behaviour) and three related disorders (PD medication use, hobbyism and punding) were assessed. Questions related to the four ICDs form categories A–D have a range of total ICD scores from 0 to 64, while questions regarding the three related disorders form categories E–F. The total QUIP-RS score ranges from 0 to 112. Eighteen percent had an A–D score ≥ 10 or an E–F score ≥ 7, which are the cutoffs suggestive of the presence of ICDs or related disorders. The most common ICDs were PD medication overuse (12%), compulsive eating (6%), compulsive buying (6%), hypersexual behaviour (5%), punding (3%) and gambling (2%).
Depression
The prevalence of depression was 25%. Pre-motor onset of depression was seen in 3%. Post-motor onset was observed in 22% of cases, with 13% developing it between 5 and 10 years after motor symptom onset and 9% developing it more than 10 years after motor symptom onset. The mean duration of onset of post-motor depression was 8.5 ± 2.6 years.
Cognitive dysfunction
The prevalence of cognitive dysfunction was 64%, and all cases developed after the onset of motor symptoms. The screening for cognitive dysfunction was performed by using the MoCA test. The mean MoCA score was 22.8 ± 5.4. Sixty-four percent had a MoCA score less than 26, which was suggestive of cognitive impairment.
Restless leg syndrome
The prevalence of RLS was 18%, and all cases developed after the onset of motor symptoms. The presence and severity of RLS were assessed using the RLS-RS, which has a score ranging from 0 to 40. The mean RLS-RS score was 1.9 ± 4.7. Twelve percent had mild RLS (score <10), 5% had moderate RLS (score 11–20) and 1% had severe RLS (score 21–30).
Non-motor symptom onset compared to the motor onset
Overall, pre-motor onset of NMS was observed in 24% of patients and post-motor onset in 70%. Further, the patients were classified into brain-first or body-first subtypes based on the presence of pre-motor RBD. Eight percent had the presence of pre-motor RBD and were classified as the body-first subtype, whereas 84% exhibited RBD concurrent with or after the onset of motor symptoms or had not yet developed RBD, and these patients were classified as the brain-first subtype. A timeline and a scatter plot of NMS are depicted in Figures 2 and 3. The characteristics of NMS in relation to motor symptom onset (pre-motor and post-motor onset of NMS) are summarized in Tables 2 and 3.
Temporal profile of onset of non-motor symptoms with respect to motor symptom onset. The extent of each box implies the range of duration of onset of the respective non-motor symptom. The percentages within the box represent the frequency of the non-motor symptoms prior to and after the onset of motor symptoms. OH = orthostatic hypotension; RBD = rapid eye movement sleep behaviour disorder.
Scatter plot of the onset of non-motor symptoms with respect to the onset of motor symptoms in each patient. RBD = rapid eye movement sleep behaviour disorder.
Characteristics of non-motor symptoms (NMS) in patients with pre-motor onset of NMS
ICDs = impulse control disorders; RBD = rapid eye movement sleep behaviour disorder.
Characteristics of non-motor symptoms (NMS) in patients with post-motor onset of NMS
ICDs = impulse control disorders; RBD = rapid eye movement sleep behaviour disorder.
Discussion
NMS are crucial for understanding disease progression, as they manifest in all phases of PD, from the pre-motor phase to the early and advanced post-motor phases. However, the variability among patients, the lack of specificity and the different rates of progression of each NMS make it challenging to establish a definitive timeline. There is a paucity of literature regarding the timeline of NMS appearance and evolution in the pre-motor phase and in the early, advanced post-motor phases of PD. For this reason, we took advanced PD, that is, a duration of greater than 10 years of motor symptoms, so that the disease had sufficient time to manifest the NMS.
In our study, 94% of participants had at least one NMS, with 39% experiencing more than three NMS. The prevalence of NMS in PD ranges from 80% to 100%, according to various studies. A study by Tapdia et al. revealed the prevalence of NMS as 97.4%. Sleep disorders were the most commonly affected NMS domain, followed by gastrointestinal disturbances and perceptual issues. A positive correlation was also found between the Non-motor Symptom Scale and the UPDRS motor score, PDQ-39, modified H&Y score and disease duration, indicating that the prevalence and severity of NMS increase with advanced disease. Reference Tapdia, Kumar and Yadav7 Another study by Ravan et al. also showed that the number of NMS progressively increased as modified H&Y stages increased. The higher number of NMS is thought to be related to the worsening of motor symptoms. Reference Ravan, Ahmad, Chabria, Gadhari and Sankhla8 The higher burden of multiple NMS in our study could probably be ascribed to the fact that all patients in our cohort were in the advanced stages of the disease.
Evidence from the current literature also suggests that the type of NMS varies according to many factors, including age, gender and ethnicity. Patwardhan et al. reported a higher prevalence of NMS in early-onset PD patients compared to healthy controls. Reference Patwardhan, Kamble, Bhattacharya, Holla, Yadav and Pal9 Ou et al. showed that the number of NMS increased over a consecutive 3-year period and was positively correlated with advancing age and motor progression. Reference Ou, Hou and Wei10 Our study found that patients with more than three NMS were predominantly of advanced age. The effect of age on NMS burden is probably due to the contribution of older age to the faster progression of motor disability and reduced responsiveness to dopaminergic agents.
Current studies also indicate a predilection of the female gender for NMS involving mood, sleep and cardiovascular domain and a predilection of the male gender with sexual dysfunction. Reference Sauerbier, Lenka, Aris and Pal11 Our study did not show any significant correlation between gender and the above NMS (p > 0.05). This could be due to the low prevalence of cardiovascular and mood disorder-related NMS in our study.
The most frequent NMS in our study were RBD (63%), constipation (51%) and urinary dysfunction (55%). This is in concordance with many previous studies from India, which show a predominance of the following NMS in PD: constipation, sleep disturbances, anxiety and urinary disturbances. Reference de Souza, Kakode, D.’Costa and Bhonsle12,Reference Kumar, Vallampalli, Sangamithra and Prasad13 Several factors, including sociocultural habits, nutritional status, co-morbidities, environmental exposure, physical activity, genetic background and pharmacogenetics, have been shown to influence the occurrence of NMS in different ethnic groups.
RBD, constipation, hyposmia, urinary dysfunction, psychosis and depression had pre-motor onset but were more prevalent in the post-motor period, whereas orthostatic hypotension and ICDs were present exclusively in the post-motor period. In the pre-motor phase, symptoms such as hyposmia, RBD, constipation and mood changes (depression and anxiety) are most frequently reported. These symptoms often manifest many years before motor impairment and may serve as early biomarkers for PD. Reference Goldman and Postuma14 Symptoms such as cognitive decline, autonomic dysfunction (like orthostatic hypotension, urinary dysfunction) and visual hallucinations are more frequently present after motor symptom onset but can be present during the pre-motor phase. Reference Siderowf and Lang15
The severity of NMS through the course of the disease also appears to be affected by targeted interventions as reported by Mishra et al., where the severity of NMS significantly reduced after bilateral subthalamic nucleus deep brain stimulation surgery in sleep, mood disorders and cognitive domains (except memory) along with a significant reduction in ICDs. Reference Mishra, Kamble, Bhattacharya, Yadav, Srinivas and Pal16 Similar to motor fluctuations, NMS also exhibits daily fluctuations known as non-motor fluctuations (NMF), which may impact the course of the disease. Mujahid et al. reported that NMF was observed in 39.8% of patients and was associated with longer disease duration, higher levodopa doses, longer levodopa intake, greater motor severity, the presence of motor fluctuations, higher NMS burden and poor quality of life. Reference Mujahid, Holla, Kamble, Yadav, Pal and Mahale17
In our study, 40% had tremor-dominant, 54% had akinetic-rigid and 6% had indeterminate subtypes of PD. Kumar et al. reported that 36.9% had tremor-dominant PD, 29.3% had the akinetic-rigid variant and 33.6% had a mixed variant of PD. There was a positive correlation between total NMS scores and age, stage of the disease, duration of the disease and individual UPDRS scores. Reference Kumar, Patil and Singh18 Another study by Ba et al. found a significant correlation between the Postural Instability and Gait Difficulty (PIGD) subtype and higher NMS burden, with the PIGD group having a higher prevalence in most NMS domains. Reference Ba, Obaid, Wieler, Camicioli and Martin19
In our study, the mean duration of pre-motor RBD was 9.1 ± 7.9 years before the onset of motor symptoms. A study by Iranzo et al. showed that RBD precedes the development of parkinsonian motor symptoms by an average of 11.5 years and that most patients with premotor RBD developed PD, while some might develop multiple system atrophy or dementia with Lewy bodies. Reference Iranzo, Molinuevo, Santamaria, Serradell, Martí and Valldeoriola20 Another study by Kalaitzakis et al. showed that the caudo-rostral spreading of alpha-synuclein pathology did not occur in 47% of the patients with PD. Reference Kalaitzakis, Graeber, Gentleman and Pearce21 This might explain why pre-motor RBD does not occur in all patients with PD and why some patients may have a post-motor onset of RBD. The presence of pre-motor RBD is associated with a greater burden of other NMS, such as hyposmia, cognitive symptoms, pain, constipation and dysautonomia, as well as a greater occurrence of bilateral motor symptoms and faster progression of motor impairment. Reference Boeve, Silber, Ferman, Lin and Benarroch22
Constipation was present in 59% of the patients, with pre-motor onset in 8%. A study by Kaye et al. demonstrated that constipation can predate motor symptoms by many years. Reference Kaye, Gage, Kimber, Storey and Trend23 This can probably be explained by pathological studies by Braak et al., which have demonstrated that alpha-synuclein deposition occurs in the dorsal motor nucleus of the vagus and the enteric nervous plexuses before the involvement of the substantia nigra. Reference Braak, de Vos, Bohl and Del Tredici24
Pre-motor urinary dysfunction was present in 1%. Kauffmann et al. showed that symptoms of dysautonomia, including orthostatic hypotension and urinary dysfunction, can precede the motor symptoms of PD in some instances. Reference Kaufmann, Nahm, Purohit and Wolfe25
Pre-motor onset of depression was present in 3%. The duration of pre-motor depression ranged from 10 years before to 1 year before motor symptom onset. A study by Leentjens et al. found that depressive symptoms predated the motor symptoms of PD by an average of 10 years. Reference Leentjens, Van den Akker, Metsemakers, Lousberg and Verhey26 The degeneration of the hypothalamus, locus coeruleus, dorsal raphe nucleus and ventral tegmental area, as well as the deposition of alpha-synuclein, leading to malfunction in the dopaminergic, noradrenergic and serotonergic systems, has been implicated as a cause of depression in patients with PD. Reference Remy, Doder, Lees, Turjanski and Brooks27
According to the body-first and brain-first hypothesis by Horsager et al., the pattern of NMS onset differs based on the initial site and spread of alpha-synuclein deposition. Reference Horsager, Andersen and Knudsen28 In the body-first subtype, the pathology likely starts in the peripheral autonomic nervous system and propagates via the vagus nerve to the dorsal motor nucleus of the vagus and pontine structures before involving the substantia nigra. This results in the appearance of RBD before the onset of motor symptoms of PD. Conversely, in the brain-first subtype, the pathology originates probably in the olfactory bulb or amygdala and spreads initially to the ipsilateral hemisphere and nigrostriatal pathway, giving rise to motor symptoms, and it eventually involves the brainstem, sympathetic trunk and the enteric and autonomic nervous system, thereby giving rise to NMS such as RBD, constipation and other autonomic symptoms. Eight percent had pre-motor onset of RBD. According to a study by Schenck et al., pre-motor RBD had an 81% risk of progression to a neurodegenerative disorder. Reference Schenck, Boeve and Mahowald29 Pre-motor RBD is considered a key clinical marker of the body-first subtype.
Understanding the patterns and chronology of various NMS can guide us in tailoring therapeutic strategies and improving disease management. For example, early identification of various NMS can help provide care for these NMS before they become too severe and bothersome. In patients with psychosis, behavioural disturbances or ICD, one may have to avoid initiating or increasing the dose of dopamine agonists, amantadine and anticholinergics, as they may worsen these NMS. Patients with constipation and bladder dysfunction may have worsening of these symptoms if they are added on anticholinergics like trihexyphenidyl or amantadine for tremor or motor fluctuations, respectively. Patients with RBD may experience worsening with the addition of selective serotonin reuptake inhibitors and other antidepressants prescribed for depression. Also, patients with RBD and constipation have been observed to be more likely to develop psychosis and cognitive impairment, and hence, interventions that can precipitate or worsen these may be avoided.
There are certain limitations in our study. As the patients are having long-term PD and the data collection was at a single point, there is significant recall bias. We attempted to circumvent this by involving caregiver input and referring to any available medical records to document the timeline of NMS onset. Moreover, the questionnaire administered to assess the severity of various NMS may be marred by subclinical cognitive impairment that patients may have, making it difficult for them to reliably respond to the questionnaire. Here, input from the caregiver was also obtained to reduce the error. As the medications prescribed for PD may themselves cause many of the NMS, the role of medication changes on the temporal profile of NMS cannot be ruled out. However, the patients were on stable medications for at least 3 months when the data were collected.
Conclusion
PD is a complex neurodegenerative disorder that has characteristic motor symptoms but clinically heterogeneous NMS. While most subjects developed one or more NMS, the occurrence of NMS prior to the onset of motor symptoms was present in only about one-fourth of the patients. RBD is the most prevalent NMS, and the presence of RBD in the pre-motor phase serves as a hallmark of the body-first subtype of PD. Understanding these patterns can guide tailored therapeutic strategies and improve disease management.
Acknowledgements
None.
Author contributions
Sricharan Vijayakumar contributed to the conception, organization, and execution of the research project; the design and execution of the statistical analysis; and the preparation of the first and final drafts of the manuscript. Nitish Kamble, Vikram V. Holla, Rohan Mahale, and Ravi Yadav contributed to the conception and organization of the research project and to the review and critique of the statistical analysis and the manuscript. Pramod Kumar Pal contributed to the conception and organization of the research project, the design and review of the statistical analysis, and the review and critique of the manuscript.
Funding statement
No specific funding was received for this work.
Competing interests
There are no conflicts of interest relevant to this work.
Ethical standards
Institute Ethics Committee approval was obtained (number: NIMH/DO/IEC/(BS & NS DIV)/2022) for the study, and informed consent was obtained from the patients or their caregivers for participation in the study and publication.
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.
