Dysphagia in Parkinson´s disease. A 5-year follow-up study

Vol.:(0123456789) Neurological Sciences https://doi.org/10.1007/s10072-025-08027-8 ORIGINAL ARTICLE Dysphagia inParkinson´s disease. A5‑year follow‑up study DiegoSantos‑García1,2,3,4 · TeresadeDeusFonticoba5· SilviaJesús6,7· MarinaCosgaya8· JuanGarcíaCaldentey9· NuriaCaballol10· InesLegarda11· JorgeHernándezVara7,12· IriaCabo13· LydiaLópezManzanares14· IsabelGonzálezAramburu7,15· MariaA. ÁvilaRivera16· VíctorGómezMayordomo17· VíctorNogueira18· JulioDotorGarcía‑Soto19· CarmenBorrué20· BertaSolanoVila21· MaríaÁlvarezSauco22· LydiaVela23· SoniaEscalante24· EstherCubo25· ZebenzuiMendoza26· IsabelPareés27· PilarSánchezAlonso28· MariaG.AlonsoLosada29· NuriaLópezAriztegui30· ItziarGastón31· JaimeKulisevsky7,32· ManuelSeijo13· CaridadValero33· RubenAlonsoRedondo18· CarlosOrdás34· ManuelMenéndez‑González35· DarrianMcAfee36· PabloMartinez‑Martin7· PabloMir6,7,37· COPPADIS Study Group Received: 17 August 2024 / Accepted: 25 January 2025 © The Author(s) 2025 Abstract Background and objective Dysphagia at time of diagnosis suggests atypical parkinsonism instead Parkinson´s disease (PD). Our aim was to analyze the frequency of dysphagia in patients with early PD comparing with a control group and to identify related factors. Patients and methods Patients with early PD (≤ 2years from symptoms onset) who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated annually for 5years from the Spanish cohort COPPADIS were included in this prospective study. Controls were assessed at baseline and at 2-, 4-, and 5-year follow-up. Dysphagia was defined as a score ≥ 1 in the item 20 of the Non-Motor Symptoms Scale (NMSS). Results Dysphagia was more frequent at baseline in PD patients (19.6% [36/184]; 62.3 ± 8.3years old; 56.8% males) than in controls (5.3% [11/206]; 60.9 ± 8.3years old; 50% males) (p < 0.0001) and in all visits as well (p < 0.0001). A worse quality of sleep (Parkinson´s Disease Sleep Scale; OR = 0.974; p = 0.005), a greater impulse-control behavior (ICB) (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale; OR = 1.066; p = 0.014), and non-motor symptoms burden (Non-Motor Symptoms Scale; OR = 1.016; p = 0.021) were independent factors associated with dysphagia at baseline. In those subjects with dysphagia, no differences were observed between patients and controls in the mean NMSS-item 20 overtime, and it didn´t change throughout the follow-up. Conclusion Dysphagia was frequent in early PD patients compared to controls. However, it was minor and did not progress over time. Sleep, ICB, and non-motor symptoms burden were related to dysphagia. Keywords Cohort· Early· Dysphagia· Impulse control disorder· Non-motor symptoms· Parkinson's disease Introduction Dysphagia is highly prevalent in Parkinson disease (PD) but is not typically identified nor treated until later in the disease process. In fact, severe dysphagia within the first 5years is a known red flag for diagnosis of PD [1]. Dysphagia in PD varies significantly when it is based on subjective than on objective measurements [2]. A recent meta-analysis found a pooled prevalence rate of dysphagia in PD of 36.9% (95% CI: 30.7–43.6%), whereas instrumental examination showed a higher prevalence (57.3%, 95% CI: 44.3–69.1%) [3]. Dysphagia is associated with older age, male sex, lower body mass index, longer disease duration, higher Hoehn and Yahr (H&Y) stage and levodopa equivalent daily dose (LEDD), PIGD (Postural Instability Gait Difficulties) subtype, severe motor symptoms, cognitive impairment, drooling, higher levels of depression, and lower quality of life (QoL) [3–5]. Furthermore, dysphagia reduces quality of life (QoL), complicates medication intake, predicts a worse outcome in latestage PD [6] and plays a role in weight loss and recurrent of airway infections [7]. However, dysphagia can be present at early phases of PD as well and often is underestimated. Extended author information available on the last page of the article Neurological Sciences In fact, dysphagia has not been well studied in early PD [8]. In a recent meta-analysis about dysphagia prevalence and associated factors in PD involving 58 studies [3], the mean disease duration was 7.4 (range from 0.5 to 17.8), and only 2 studies had a mean disease duration of 2years or less [9, 10]. The prevalence of dysphagia in a cohort of early drug-naïve PD patients from the PPMI database was 12.3% (49/398) with a mean disease duration of 0.5 ± 0.5years [9]. Dysphagia occurred in 20.1% (349/1738) of the patients from the United Kingdom Tracking Parkinson's Study with recent onset symptoms (mean disease duration 1.3 ± 0.9years) [10]. However, both studies were cross-sectional and without a control group. Thus, more information about the role of dysphagia in early PD is needed. The aim of the present study was to analyze the frequency of dysphagia in patients with early PD, and it to compare with a control group. Specifically, we identified the prevalence of dysphagia, the burden of the symptom, and its change over a 5-year span in patients and controls. Moreover, we identified factors related to dysphagia and analyzed the correlation of dysphagia with drooling, hypomimia, and speech problems. Material andmethods Patients with early PD (≤ 2years from symptoms onset) who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated annually for 5years from the Spanish cohort COPPADIS [11] were included in this longitudinal prospective study. This is a multi-center, observational, prospective, 5-year follow-up study designed to analyze disease progression in a Spanish population of PD patients. Methodology about COPPADIS-2015 study can be consulted in https:// bmcne urol. biome dcent ral. com/ ar tic les/https:// doi. org/ 10. 1186/ s128830160548-9 [12]. All patients included at baseline were diagnosed according to UK PD Brain Bank criteria [13]. Exclusion criteria were: atypical parkinsonism; Mini Mental State Examination [MMSE] < 26; age < 18 or > 75years; inability to read or understand the questionnaires; to receive any advanced therapy (continuous infusion of levodopa or apomorphine; and/or with deep brain stimulation at baseline); and the presence of comorbidities, sequelae, or any other disorder that could interfere with the assessment. Control subjects from the COPPADIS cohort assessed at baseline and at 2-, 4-, and 5-year follow-up were also included. At each visit, to have dysphagia was defined as a nonzero score (from 1 to 12) in the item 20 (“Does the patient having difficulty swallowing?”) of the Non-Motor Symptoms Scale (NMSS) [14]. A score ≥ 6 was considered as relevant dysphagia burden (from often x severe or frequent x moderate [6 points] to always x severe [12 points]). The same method was used to define drooling, according to the NMSS-item 19 (Does the patient dribble saliva during the day?). Regarding speech problems, PD patients were classified in 5 groups according to the item-18 of the Unified Parkinson´s Disease Rating Scale – part III (UPDRS-III): 0 = Normal; 1 = Slight loss of expression, diction and/or volume; 2 = Monotone, slurred but understandable; moderately impaired; 3 = Marked impairment, difficult to understand; 4 = Unintelligible [15]. The UPDRS-III was also used to define facial expression (item-19): 0 = Normal; 1 = Minimal hypomimia, could be normal "Poker Face"; 2 = Slight but definitely abnormal diminution of facial expression; 3 = Moderate hypomimia; lips parted some of the time; 4 = Masked or fixed facies with severe or complete loss of facial expression; lips parted 1/4 inch or more. Information on sociodemographic aspects, factors related to PD, and treatment was collected. The H&Y, UPDRS-III and part IV (UPDRS-IV), NMSS and ADLS (Schwab & England Activities of Daily Living Scale) were applied annually in PD patients. Other data about motor status, non-motor symptoms (NMS) and QoL were assessed at V0, V2, V4, and V5 using different validated scales: Freezing of Gait Questionnaire (FOGQ); Beck Depression InventoryII (BDI-II); Parkinson's Disease Sleep Scale (PDSS); Neuropsychiatric Inventory (NPI); Questionnaire for ImpulsiveCompulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS); Visual Analog Scale-Pain (VAS-Pain); Visual Analog Fatigue Scale (VAFS]); the 39-item Parkinson's disease Questionnaire (PDQ-39); the EUROHIS-QOL 8-item index (EUROHIS-QOL8) [12]. In patients with motor fluctuations, the motor assessment was made during the OFF state (without medication in the last 12h) and during the ON state. The assessment was only performed without medication in patients without motor fluctuations. Motor phenotype, motor fluctuations, FOG, falls, and major depression were defined in the COPPADIS protocol according to the literature and scales used [12]. Moreover, impulse control behaviors (ICBs) were considered, both impulse control disorders (ICDs) (pathological gambling, compulsive shopping, hypersexuality, and compulsive eating behavior) and compulsive behaviors (CBs) (punding, hobbyism, and dysregulation dopaminergic syndrome). We applied previously published cutoff points of the QUIP-RS: gambling ≥ 6, buying ≥ 8, sex ≥ 8, eating ≥ 7, hobbyism-punding ≥ 7 [16]. For dopaminergic dysregulation syndrome (DDS), we accounted for the researcher´s criteria, since an established cutoff does not exist [17]. Patients suffering from at least one ICD and/ or CB were considered as patients presenting ICB. The same evaluation as for the patients, except for the motor assessment, was performed in control subjects at the same visits (V0; V2; V4; V5). LEED was calculated based on the literature [18]. Neurological Sciences Statistical analysis Data were processed using SPSS 20.0 for Windows. Different variables were expressed as quantitative and/or qualitative variables. Distribution of variables was verified by one-sample Kolmogorov–Smirnov test. All subjects from the COPPADIS cohort who met defined criteria were selected for comparisons at the baseline visit. However, it was mandatory that all selected participants must have been evaluated at all visits to compare the changes in the follow-up: V0; V1 (at 1-year); V2 (at 2-year); V3 (at 2-year); V4 (at 4-year); V5 (at 5-year). For comparisons between subjects (patients vs controls) and from a different group (with vs without dysphagia) at each visit (V0; V2; V4; V5), the Student's t-test, Mann–Whitney U, Chi square, or Fisher test were applied. Binary regression models were used to determine independent factors associated with dysphagia (dysphagia as dependent variable). Variables with univariate associations with p-values < 0.20 were included in a multivariable model, and a backwards selection process was used to remove variables individually until all remaining variables were significant at the 0.10 level except age, gender, disease duration and LEDD, added as covariates. Spearman’s or Pearson’s correlation coefficient, as appropriate, were used for analyzing the relationship between dysphagia and drooling, speech problems, and hypomimia. Correlations were considered weak for coefficient values ≤ 0.29, moderate for values between 0.30 and 0.59, and strong for values ≥ 0.60. General linear model (GLM) repeated measures were used to test for changes in the mean NMSS-item 20 score in PD patients and in controls. In the models, age, gender, disease duration, and LEED at each visit were included as covariates for PD patients and age and gender for controls. The Bonferroni method was used as a post-hoc test after ANOVA. Cohen´s d formula was applied for measuring the effect size. It was considered: < 0.2 – Negligible; 0.2 – 0.49 – Small; 0.50 – 0.79 – Moderate; ≥ 0.80 – Large. The value of p was considered significant when it was < 0.05. Standard protocol approvals, registrations, andpatient consents For this study, we received approval from the Comité de Ética de la Investigación Clínica de Galicia from Spain (2014/534; 02/DEC/2014). Written informed consents from all participants (patients and controls) in this study were obtained. Results A total of 184 early PD patients (62.3 ± 8.3years old; 56.8% males) and 206 controls (60.9 ± 8.3years old; 50% males) were included. Mean disease duration was 1.3 ± 0.7years. At baseline, dysphagia was significantly more frequent in PD patients than controls (19.6% vs 5.3%; p < 0.0001) and mean score of the NMSS-item 20 was significantly higher in PD patients (0.4 ± 1 vs 0.1 ± 0.8; p < 0.0001). However, only one patient had relevant dysphagia (NMSS-item 20 ≥ 6) and no differences were detected in the NMSS-item 20 score in patients compared to controls when only subjects with dysphagia were included (2.1 ± 1.3 vs 2.4 ± 2.4; p = 0.685). At V0 and comparing patients with vs without dysphagia, a higher score on the UPDRS-IV (1.4 ± 1.6 vs 0.9 ± 1.4; p = 0.014), FOGQ (3.3 ± 3.8 vs 1.9 ± 2.9; p = 0.010), NMSS (62.2 ± 35.3 vs 35.7 ± 30.8; p < 0.0001), BDI-II (10.9 ± 7.8 vs 7.8 ± 7.1; p = 0.019), QUIP-RS (7.8 ± 14 vs 2.3 ± 4.9; p = 0.007), VASF – physical (3.6 ± 2.7 vs 2.4 ± 2.7; p = 0.007), VASF – mental (3.4 ± 2.8 vs 1.8 ± 2.3; p = 0.001), and PDQ-39SI (23.2 ± 14.4 vs 12.6 ± 11.3; p < 0.0001) and a lower score on the PDSS (98.8 ± 30.2 vs 120.8 ± 25.7; p < 0.0001) and ADLS (87.5 ± 11.6 vs 92.8 ± 8.2; p = 0.028) were detected in those patients with dysphagia (Table1). Specifically, FOG (36.1% vs 18.2%; p = 0.021), falls (22.2% vs 6.2%; p = 0.007), drooling (55.6% vs 29.7%; p = 0.015), and to have any ICB (21.4% vs 6.6%; p = 0.024) were more frequent in patients with dysphagia. Both ICDs and CBs were associated with dysphagia with compulsive eating the most significant ICB associated with dysphagia (14.3% in patients with dysphagia vs 1.5% in those without dysphagia; p = 0.008) (Fig.1). Dysphagia correlated moderately with drooling (r = 0.348; p < 0.0001) but not with speech problems (r = −0.115; p = 0.445) or hypomimia (r = −0.098; p = 0.515). In a regression binary model (dysphagia at baseline as dependent variable), the factors identified as independently associated with dysphagia were a worse quality of sleep (PDSS; OR = 0.974; p = 0.005) and a greater ICB (QUIP-RS; OR = 1.066; p = 0.014) and NMS burden (NMSS; OR = 1.016; p = 0.021) (Table2). The association between the QUIP-RS and dysphagia was maintained after adjusting to be receiving a dopamine agonist (QUIP-RS; OR = 1.073; p = 0.008). Specifically, to have any ICD as a whole (OR = 3.848; 95% CI 1.246 – 11.887; p = 0.019), any ICD (OR = 5.696; 95% CI 1.527 – 21.245; p = 0.010), any CB (OR = 4.746; 95% CI 1.337 – 16.848; p = 0.016), compulsive eating (OR = 11.25; 95% CI 1.951 – 64.871; p = 0.007), hobbyism-punding (OR = 4.4; 95% CI 1.002 – 11.575; p = 0.007), and DDS (OR = 13.364; 95% CI 1.347 – 132.553; p = 0.027) were associated with dysphagia, but none were after adjusting to covariates of the model. At V5 (N = 116), the QUIP-RS was associated again to dysphagia (OR = 1.042; 95% CI 1.001 – 1.086; p = 0.046), but it was not significant after adjustment to covariates (p = 0.274). In the follow-up analysis (all data in all visits for all participants, from V0 to V5), 89 patients (61 ± 8.6years old; 53.9% males) and 72 controls (63.1 ± 6.7years old; 50% males) were included. Dysphagia was clearly more frequent Neurological Sciences Table 1 Disease related characteristics, motor and non-motor symptoms, autonomy for activities of daily living and quality of life in PD patients with vs without dysphagia at baseline (N = 184) The results represent percentages, mean ± SD or median [p25, p75]. Chi-squared, Fisher and ANOVA test were applied. Data about H&Y and UPDRS-III are during the OFF state (first thing in the morning without taking medication in the previous 12h) ADLS Schwab and England Activities of daily living Scale), BDI-II Beck Depression Inventory-II, CB compulsive behavior, FOGQ Freezing of Gait Questionnaire, FOG freezing of gait, ICB impulse control behavior, ICD impulse control disorder, NMSS Non-Motor Symptoms Scale, NPI Neuropsychiatric Inventory, PD Parkinson´s disease, PD-CRS Parkinson’s Disease Cognitive Rating Scale, PDSS Parkinson’s Disease Sleep Scale, PIGD Postural Inestability Gait Dificulty, QUIP-RS Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale, UPDRS Unified Parkinson’s Disease Rating Scale, VAFS Visual Analog Fatigue Scale, VAS-Pain Visual Analog Scale-Pain All cohort (N = 184) Without dysphagia (N = 148) With dysphagia (N = 36) p Age 62.3 ± 8.3 62.2 ± 8.4 62.8 ± 8.1 0.702 Males (%) 56.8 58.1 52.8 0.346 Disease duration (years) 1.3 ± 0.7 1.3 ± 0.7 1.1 ± 0.8 0.207 L-dopa daily dose (mg) 317 ± 247.4 317.1 ± 252.5 316.6 ± 228.1 0.753 Weight (kgs) 75.8 ± 13.5 75.7 ± 14.2 76 ± 10.9 0.660 Motor phenotype (%): 0.777 - Tremoric dominant 58.7 57.5 63.9 - PIGD 28.3 29.7 22.2 - Indeterminate 13 12.8 13.9 Hoehn & Yahr – OFF 2 [1.5,2] 2 [1.5,2] 2 [1.5,2] 0.440 - Stage 3 – 5 (%) 2.5 3.1 0 0.299 UPDRS-III—OFF 19.1 ± 9.1 19.2 ± 9.4 18.8 ± 7.6 0.814 UPDRS-IV 1 ± 1.4 0.9 ± 1.4 1.4 ± 1.6 0.014 - Motor fluctuations (%) 8.7 6.8 16.7 0.060 FOGQ 2.2 ± 3.1 1.9 ± 2.9 3.3 ± 3.8 0.010 - FOG (%) 21.7 18.2 36.1 0.021 - Falls (%) 9.4 6.2 22.2 0.007 MMSE 29.3 ± 1 29.4 ± 1 29.1 ± 1.1 0.242 PD-CRS total score 90.7 ± 14.9 90.8 ± 15.1 90.6 ± 14.3 0.858 PD-CSR FS sub-score 62.8 ± 13.5 62.7 ± 13.6 63.4 ± 13.3 0.806 PD-CRS PC sub-score 27.9 ± 3.5 28.1 ± 3.3 27.2 ± 4.3 0.761 NMSS 40.9 ± 33.4 35.7 ± 30.8 62.2 ± 35.3 < 0.0001 - Drooling (%) 34.8 29.7 55.6 0.004 - Speech problems (%) 39 38 42.9 0.368 - Hypomimia (%) 76.1 81.2 64.3 0.192 BDI-II 8.4 ± 7.4 7.8 ± 7.1 10.9 ± 7.8 0.019 - Major depression (%) 16.3 14.2 25 0.096 NPI 5.3 ± 6.8 4.7 ± 6.1 7.7 ± 8.5 0.063 QUIP-RS 3.3 ± 7.6 2.3 ± 4.9 7.8 ± 14 0.007 - Any ICB (ICD or CB) (%) 9.1 6.6 21.4 0.024 - Any ICD (%) 6.1 3.7 17.9 0.014 - Any CB (%) 6.7 4.4 17.9 0.022 PDSS 116.6 ± 27.9 120.9 ± 25.7 98.8 ± 30.2 < 0.0001 VAS-PAIN 2.7 ± 2.9 2.6 ± 2.8 3 ± 3.1 0.467 VASF − physical 2.6 ± 2.7 2.4 ± 2.7 3.6 ± 2.7 0.007 VASF – mental 2.1 ± 2.5 1.8 ± 2.3 3.4 ± 2.8 0.001 ADLS 91.1 ± 9.1 92 ± 8.2 87.5 ± 11.6 0.028 PDQ-39SI 14.7 ± 12.6 12.6 ± 11.3 23.2 ± 14.4 < 0.0001 EUROHIS-QOL8 3.8 ± 0.6 3.9 ± 0.5 3.7 ± 0.6 0.050 PQ-10 7.4 ± 1.6 7.4 ± 1.6 7.3 ± 1.6 0.424 Neurological Sciences in PD patients than controls (p < 0.0001 at V0, V2, V4 and V5): 23.6% at V0, 28.1% at V1, 28.1% at V2, 29.2% at V3, 25.8% at V4, and 32.6% at V5 in patients; 5.6% at V0, 4.2% at V2, 2.8% at V4, and 6.9% at V5 in controls (Fig.2A). Mean score of the NMSS-item 20 was significantly higher in PD patients than controls (p < 0.0001 in all visits): V0, 0.6 ± 1.2 vs 0.2 ± 1.2; V2, 0.7 ± 1.6 vs 0.2 ± 1.1; V4, 0.7 ± 1.5 vs 0.1 ± 0.5; V5, 0.7 ± 1.5 vs ± 0.2 ± 0.7. However, no statistically significant differences (p ≥ 0.05) between PD patients and controls in the NMSS-item 20 score were detected in any of the visits when only subjects with dysphagia were included (Fig.2B). No differences (Cohen´s d formula < 0.2 and p > 0.05 for all analysis) in the mean NMSS-item 20 score were detected between the different visits (from V0 to V5; from V0 to V1; from V1 to V2; from V2 to V3; from V3 to V4; from V4 to V5) throughout the follow-up neither in patients nor controls. Relevant dysphagia burden was detected only in 1.1%, 6.6%, 3.3%, 6.7%, 4.5%, and 3.3% of the patients at V0, V1, V2, V3, V4, and V5, respectively. Discussion The present study observed that dysphagia is frequent in early PD patients (≤ 2years of disease duration), affecting about 1 out of 4 patients. However, dysphagia burden was low and did not progress over time, like in controls. Although many factors were associated with dysphagia in early stages of PD, only a worse quality of sleep and a greater ICB and NMS burden were independent factor associated with dysphagia. To our knowledge, this is the first time that an association between dysphagia and ICBs have been described. Fig. 1 Percentage of PD patients with dysphagia (in green) vs without dysphagia (in black) suffering from impulse and/or compulsive symptoms. Fisher test was applied. CBs, compulsive behaviors; ICBs, impulsive-compulsive behaviors; ICDs, impulse control disorders Table 2 Independent factors associated with dysphagia in PD patients at baseline (N = 184) Dependent variable: Dysphagia at baseline. OR and 95% IC are shown. a, univariate analysis; b, multivariate analysis. The model was adjusted to age, gender, disease duration and LEDD. LEDD levodopa equivalent daily dose, NMSS Non-Motor Symptoms Scale, PDSS Parkinson´s Disease Sleep Scale, QUIP-RS Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale Variables at baseline ORaORbHosmer – Lemeshow test R295% ICa95% ICbpapb PDSS 0.976 0.974 0.59 0.35 0.96 – 0.99 0.96 – 0.99 < 0.0001 0.005 QUIP-RS 1.074 1.066 1.03 – 1.13 1.02 – 1.12 0.003 0.014 NMSS 1.021 1.016 1.01 – 1.03 1.01 – 1.03 < 0.0001 0.021 Neurological Sciences Throughout the 5years of follow-up of our cohort, the prevalence of dysphagia was clearly higher in PD patients (from 23.6% at baseline to 32.6% after 5years of follow-up) than in controls (from 2.8% to 6.9%) and considerably high overall considering the fact that they had less than 2years from symptoms onset at baseline. PD is one of the important etiologies of dysphagia, showing a pooled prevalence of 35% and up to 82% using subjective measures and objective measures, respectively [2]. Differences in the methodology including dysphagia definition and the characteristics of PD populations explain the great prevalence range. Since dysphagia is considered a red flag that would suggest atypical parkinsonism [1], it is important to parse out how frequent dysphagia is in PD at diagnosis. Very little information has been published about this. Only 2 out of 58 studies about dysphagia in PD were conducted in PD patients with a disease duration ≤ 2years [3, 9, 10]. Our finding of a dysphagia prevalence of 19.6% (36 out of 184 patients) at baseline agrees with the 20.1% reported by Malek etal. [10] in 1746 patients that had been diagnosed within the preceding 3.5years (mean disease duration of 1.3years) and 20.1% (vs 3% in controls) detected by Khoo etal. [19] in 159 patients with a median disease duration of 4.4months. However, this was higher than the 12.3% reported by Polychronis etal. [9] in 398 PD patients with a mean disease duration of 0.5years. As in our study, dysphagia was recorded in all these studies [9, 10, 19] according to a question of a general scale, the SCOPA-AUT [9, 10] and the NMSQuest [19], and not with objective methods. We used a question (item 20) of the NMSS and results must be interpreted with caution because the prevalence could be higher if a more specific scale validated for the detection of dysphagia or especially objective methods were used [20]. In fact, and surprisingly, 0 out of 41 newly diagnosed PD patients had “difficulty swallowing food or drinking or problems with choking” in a study in which the NMSQuest was used [21]. Comparing to all studies conducted in early PD patients, we demonstrated that although dysphagia could be frequent even in the first 2years from symptoms onset and is clearly more common than in controls, relevant dysphagia is rare, and dysphagia burden doesn’t progress over time after a 5-year follow-up. Nonetheless, this could be a cue to differentiate parkinsonism with dysphagia is due to PD vs. an atypical parkinsonism [22]. Some factors have been identified to be associated with dysphagia in PD such as older age, male sex, lower body mass index, longer disease duration, higher H&Y stage and levodopa equivalent daily dose (LEDD), PIGD subtype, severe motor symptoms, cognitive impairment, drooling, higher levels of depression and anxiety, and lower QoL [3–5]. Many of them are related to the progression of the disease and in fact, the prevalence of dysphagia is higher in advanced PD, reaching up to more than 80% [23]. However, despite our analysis being conducted in early PD patients Fig. 2 A. Number of PD patients and/or controls with and without dysphagia at V0, V1, V2, V3, V4 and V5. At V0, V2, V4 and V5, the percentage of dysphagia was significantly higher in patients than in controls (p < 0.0001 for all analysis). The Chi-square test was applied. B. NMSS-item 20 score in PD patients with dysphagia at V0, V1, V2, V3, V4 and V5 and in controls at V0, V2, V4 and V5. Mean and standard deviation are shown. No significant differences (p > 0.05) were detected between patients and controls in any visit or between the different visits throughout the follow-up in either patients and controls. T-Student and/or General linear model (GLM) repeated measure was adjusting to age, gender, disease duration and levodopa equivalent daily dose at each visit Neurological Sciences (mean disease duration 1.3 ± 0.7) with 97.5% in the stage 2 of H&Y, significant differences between patients with and without dysphagia were observed in motor aspects (UPDRSIV, FOG and falls), NMS including drooling, mood (BDI-II), ICBs (QUIP-RS), sleep (PDSS), and fatigue (VAFS), disability (ADLS), and PD related QoL (PDQ-39SI). Of them, only a worse quality of sleep and a greater ICB and NMS burden were independent factors associated with dysphagia. Interestingly, Marano etal. [23] observed that excessive daytime sleepiness was strongly related to the development of swallowing impairment after a 3-year follow-up in a retrospective study conducted in early-stage PD patients who were not on dopaminergic treatment at baseline. Drooling and dysphagia are related [3, 24], as we found, and can affect the sleep. Mean total sleep time (minutes) was 350.8 ± 79.3 in 5 PD patients with dysphagia compared to 406.4 ± 119.9 in 16 PD patients without dysphagia in a study conducted in 21 PD patients vs 18 controls with all-night sleep video-EEG and electromyography information collected [25]. Moreover, sleep is one of the items commonly affected in studies analyzing the QOL related to swallowing [26]. NMS burden was also related to dysphagia in our cohort. A greater burden of NMS in patients with dysphagia could suggest the presence of a phenotype with more non-motor involvement. Additionally, the presence of dysphagia could be a useful indication to investigate the presence of other NMS. The pathophysiology of dysphagia is complex and many areas of the brain and even in the peripheral nervous system could be involved [27], which could explain the greater NMS burden that we found associated with dysphagia. On the other hand, our limited knowledge on the relationship between dysphagia and ICB is more difficult to explain. Importantly, this is the first time described, but probably, the first time explored as well [28]. As we did not collected information to classify the patient’s swallow difficulty (i.e., oral phase vs pharyngeal phase vs esophageal phase), all possible suggestions are purely speculative. Dysphagia is also associated with depression and anxiety due to (i) the severity and impact of the symptom itself, (ii) the underlying cause, and/or (iii) inappropriate responses to swallowing problems leading to subsequent impulsive eating behaviors or other maladaptive behaviors, among other reasons [29]. To think of a frontal lobe dysfunction as a cause [30], we did not observe differences in cognitive function between PD patients with vs without dysphagia, like in some studies [3]. Interestingly, in the ICARUS study [31], patients who were ICD-positive at study baseline had more severe NMS (including mood and sexual function) and depression, as well as had poorer sleep quality and reduced PD-related QoL compared with those who were ICD-negative, like in our cohort with those patients with dysphagia. This possible relationship between ICBs and dysphagia should be properly explored. In favor of it, a significant association with the QUIP-RS was obtained again after the 5-year followup in this cohort of early PD patient. When considering all the cohort, the QUIP-RS was associated to dysphagia as well (data not shown; N = 691; OR = 1.027; 95% CI 1.003 – 1.051; p = 0.027) after adjustment to age, gender, disease duration, H&Y stage, dopamine agonist treatment, UPDRSIV, NMSS, and PDSS. Finally, and regarding QoL, patients with dysphagia had a worse QoL according to the PDQ-39, something previously reported in a meta-analysis [3]. This reinforces the importance of dysphagia as a disabling symptom for the patient [26]. The present study has limitations. The most important, as it has been mentioned, dysphagia was defined according to subjective methods using one question of a general questionnaire (NMSS). Secondarily, mechanisms involved in dysphagia in these patients were not analyzed. However, this is frequent in the literature applying post-hoc analysis, like ours, in big cohorts [9, 10]. Second, for some analysis comparing groups (e.g., ICB), the sample was small. Third, our findings may not be applicable to all PD patients in the community clinical setting be-cause PD patients enrolled in the COPPADIS study represent a selected population with less disability at baseline than the general population (e.g., no older than 75years old, not being under a second line therapy, etc.). Finally, other markers (neuroimaging, genetic, sleep study, etc.) were not used to explain the association between dysphagia and other variables (e.g., ICD). On the other hand, and as strengths, this is a 5-year follow-up study with a comparing control group in which extensive information about sociodemographic aspects, motor and NMS, disability and QoL has been compared regarding dysphagia. For the first time, a relationship between the QUIP-RS score and dysphagia has been reported. In conclusion, dysphagia was frequent in early PD patients and clearly higher compared to controls. However, it was minor and did not progress over time. Sleep, ICB, and non-motor symptoms burden were related to dysphagia. More studies specifically designed to analyze the relationship between dysphagia with other symptoms using subjective combined with objective methods at the same time are required. Replication of this association between dysphagia and ICD is required. Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s1007202508027-8. Acknowledgements We would like to thank all patients and their caregivers who collaborated in this study. Many thanks also to Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético (https:// funda ciond egen. org/), Alpha Bioresearch (http:// www. alpha biore search. com), Instituto de Salud Carlos III and other institutions helping us.Finally, the payment of the fees for this publication has been carried out by the Galician Public Foundation for Biomedical Research INIBIC (https:// www. inibic. es/) from the aid for open access publications. Neurological Sciences COPPADIS STUDY GROUP Adarmes AD, Almeria M, Alonso Losada MG, Alonso Cánovas A, Alonso Frech F, Alonso Redondo R, Álvarez I, Álvarez Sauco M, Aneiros Díaz A, Arnáiz S, Arribas S, Ascunce Vidondo A, Aguilar M, Ávila MA, Bernardo Lambrich N, Bejr-Kasem H, Blázquez Estrada M, Botí M, Borrue C, Buongiorno MT, Cabello González C, Cabo López I, Caballol N, Cámara Lorenzo A, Canfield Medina H, Carabajal Pendón E, Carrillo F, Carrillo Padilla FJ, Casas E, Catalán MJ, Clavero P, Cortina Fernández A, Cosgaya M, Cots Foraster A, Crespo Cuevas A, Cubo E, de Deus Fonticoba T, de Fábregues-Boixar O, Díez-Fairen M, Dotor García-Soto J, Erro E, Escalante S, Estelrich Peyret E, Fernández Guillán N, Gámez P, Gallego M, García Caldentey J, García Campos C, García Díez C, García Moreno JM, Gastón I, Gómez Garre MP, Gómez Mayordomo V, González Aloy J, González-Aramburu I, González Ardura J, González García B, González Palmás MJ, González Toledo GR, Golpe Díaz A, Grau Solá M, Guardia G, Hernández Vara J, Horta-Barba A, Idoate Calderón D, Infante J, Jesús S, Kulisevsky J, Kurtis M, Labandeira C, Labrador MA, Lacruz F, Lage Castro M, Lastres Gómez S, Legarda I, López Ariztegui N, López Díaz LM, López Domínguez D, López Manzanares L, López Seoane B, Lucas del Pozo S, Macías Y, Mata M, Martí Andres G, Martí MJ, Martínez Castrillo JC, Martinez-Martin P, McAfee D, Meitín MT, Mendoza Plasencia Z, Menéndez González M, Méndez del Barrio C, Mir P, Miranda Santiago J, Morales Casado MI, Moreno Diéguez A, Muro García I, Nogueira V, Novo Amado A, Novo Ponte S, Ordás C, Pagonabarraga J, Pareés I, Pascual-Sedano B, Pastor P, Pérez Fuertes A, Pérez Noguera R, Planas-Ballvé A, Planellas L, Prats MA, Prieto Jurczynska C, Puente V, Pueyo Morlans M, Puig Daví A, Redondo Rafales N, Rodríguez Méndez L, Rodríguez Pérez AB, Roldán F, Ruíz De Arcos M, Ruíz Martínez J, Sánchez Alonso P, Sánchez-Carpintero M, Sánchez Díez G, Sánchez Rodríguez A, Santacruz P, Santos García D, Segundo Rodríguez JC, Seijo M, Sierra Peña M, Solano Vila B, Suárez Castro E, Tartari JP, Valero C, Vargas L, Vela L, Villanueva C, Vives B. Name (Last Name, First Name) Location Role Contribution Astrid Adarmes, Daniela Hospital Universitario Virgen del Rocío, Sevilla, Spain Site investigator Evaluation of participants and/or data management Almeria, Marta Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator Neuropsychologist; evaluation of participants Alonso Losada, Maria Gema Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Alonso Cánovas, Araceli Hospital Universitario Ramón y Cajal, Madrid, Spain Site investigator Evaluation of participants and/or data management Alonso Frech, Fernando Hospital Universitario Clínico San Carlos, Madrid, Spain Site investigator Evaluation of participants and/or data management Alonso Redondo, Ruben Hospital Universitario Lucus Augusti (HULA), Lugo, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Aneiros Díaz, Ángel Complejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Álvarez, Ignacio Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator Evaluation of participants and/or data management Álvarez Sauco, María Hospital General Universitario de Elche, Elche, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Arnáiz, Sandra Complejo Asistencial Universitario de Burgos, Burgos, Spain Site investigator Evaluation of participants and/or data management Arribas, Sonia Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator Neuropsychologist; evaluation of participants Ascunce Vidondo, Arancha Complejo Hospitalario de Navarra, Pamplona, Spain Site investigator Evaluation of participants and/or data management Aguilar, Miquel Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator Evaluation of participants and/or data management Ávila Rivera, Maria Asunción Consorci Sanitari Integral, Hospital General de L´Hospitalet, L´Hospitalet de Llobregat, Barcelona, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Neurological Sciences Name (Last Name, First Name) Location Role Contribution Bernardo Lambrich, Noemí Hospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Tarragona, Spain Site investigator Evaluation of participants and/or data management Bejr-Kasem, Helena Hospital de Sant Pau, Barcelona, Spain Site investigator Evaluation of participants and/or data management Blázquez Estrada, Marta Hospital Universitario Central de Asturias, Oviedo, Spain Site investigator Evaluation of participants and/or data management Botí González, Maria Ángeles Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator Neuropsychologist; evaluation of participants Borrué, Carmen Hospital Infanta Sofía, Madrid, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Buongiorno, Maria Teresa Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain Site investigator (until 2024) Nurse study coordinator Cabello González, Carolina Complejo Hospitalario de Navarra, Pamplona, Spain Site investigator Scheduling of evaluations Cabo López, Iria Complejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Caballol, Nuria Consorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Cámara Lorenzo, Ana Hospital Clínic de Barcelona, Barcelona, Spain Site investigator Nurse study coordinator Canfield Medina, Héctor Complejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, Spain Site investigator Evaluation of participants and/or data management Carabajal Pendón, Estefanía Hospital La Princesa, Madrid, Spain Site investigator (from MAR/23) Evaluation of participants and/or data management Carrillo, Fátima Hospital Universitario Virgen del Rocío, Sevilla, Spain Site investigator Evaluation of participants and/or data management Carrillo Padilla, Francisco José Hospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Casas, Elena Complejo Asistencial Universitario de Burgos, Burgos, Spain Site investigator Evaluation of participants and/or data management Catalán, Maria José Hospital Universitario Clínico San Carlos, Madrid, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Clavero, Pedro Complejo Hospitalario de Navarra, Pamplona, Spain Site investigator Evaluation of participants and/or data management Cortina Fernández, A Complejo Hospitalario Universitario de Ferrol (CHUF), Ferrol, A Coruña, Spain Site investigator Coordination of blood extractions Cosgaya, Marina Hospital Clínic de Barcelona, Barcelona, Spain Site investigator Evaluation of participants and/or data management Cots Foraster, Anna Institut d'Assistència Sanitària (IAS)—Instituí Cátala de la Salud. Girona, Spain Site investigator Evaluation of participants and/or data management Crespo Cuevas, Ane Hospital del Mar, Barcelona, Spain Site investigator Evaluation of participants and/or data management Cubo, Esther Complejo Asistencial Universitario de Burgos, Burgos, Spain Site investigator / PI Coordination at the center Evaluation of participants and/or data management Neurological Sciences Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. 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Neurological Sciences Authors and Affiliations DiegoSantos‑García1,2,3,4 · TeresadeDeusFonticoba5· SilviaJesús6,7· MarinaCosgaya8· JuanGarcíaCaldentey9· NuriaCaballol10· InesLegarda11· JorgeHernándezVara7,12· IriaCabo13· LydiaLópezManzanares14· IsabelGonzálezAramburu7,15· MariaA. ÁvilaRivera16· VíctorGómezMayordomo17· VíctorNogueira18· JulioDotorGarcía‑Soto19· CarmenBorrué20· BertaSolanoVila21· MaríaÁlvarezSauco22· LydiaVela23· SoniaEscalante24· EstherCubo25· ZebenzuiMendoza26· IsabelPareés27· PilarSánchezAlonso28· MariaG.AlonsoLosada29· NuriaLópezAriztegui30· ItziarGastón31· JaimeKulisevsky7,32· ManuelSeijo13· CaridadValero33· RubenAlonsoRedondo18· CarlosOrdás34· ManuelMenéndez‑González35· DarrianMcAfee36· PabloMartinez‑Martin7· PabloMir6,7,37· COPPADIS Study Group * Diego Santos-García [email protected] 1 Department ofNeurology, Hospital Universitario de ACoruña (HUAC), Complejo Hospitalario Universitario de ACoruña (CHUAC), C/ As Xubias 84, 15006ACoruña, Spain 2 Grupo de Investigación en Enfermedad de Parkinson y Otros Trastornos del Movimiento, INIBIC (Instituto de Investigación Biomédica de ACoruña), ACoruña, Spain 3 Hospital San Rafael, ACoruña, Spain 4 Fundación Degen, ACoruña, Spain 5 CHUF, Complejo Hospitalario Universitario de Ferrol, ACoruña, Spain 6 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain 7 CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain 8 Hospital Clínic de Barcelona, Barcelona, Spain 9 Centro Neurológico Oms 42, Palma, Spain 10 Consorci Sanitari Integral, Hospital Moisés Broggi, SantJoanDespí,Barcelona, Spain 11 Hospital Universitario Son Espases, Palma, Spain 12 Hospital Universitario Vall d´Hebron, Barcelona, Spain 13 Complejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain 14 Hospital Universitario La Princesa, Madrid, Spain 15 Hospital Universitario Marqués de Valdecilla - IDIVAL, Santander, Spain 16 Consorci Sanitari Integral, Hospital General de L´Hospitalet, L´Hospitalet de Llobregat, Barcelona, Spain 17 Neurology Department, Institute ofNeuroscience, Vithas Madrid La Milagrosa University Hospital, Vithas Hospital Group, Madrid, Spain 18 Hospital Universitario Lucus Augusti, Lugo, Spain 19 Hospital Universitario Virgen Macarena, Seville, Spain 20 Hospital Infanta Sofía, Madrid, Spain 21 Institut d‘Assistència Sanitària (IAS) - Institut Català de La Salut, Girona, Spain 22 Hospital General Universitario de Elche, Elche, Spain 23 Fundación Hospital de Alcorcón, Madrid, Spain 24 Hospital de Tortosa Verge de La Cinta (HTVC), Tortosa,Tarragona, Spain 25 Complejo Asistencial Universitario de Burgos, Burgos, Spain 26 Hospital Universitario de Canarias, San Cristóbal de La Laguna, SantaCruzdeTenerife, Spain 27 Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain 28 Hospital Universitario Puerta de Hierro, Madrid, Spain 29 Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain 30 Complejo Hospitalario de Toledo, Toledo, Spain 31 Complejo Hospitalario de Navarra, Pamplona, Spain 32 Hospital de Sant Pau, Barcelona, Spain 33 Hospital Arnau de Vilanova, Valencia, Spain 34 Hospital Rey Juan Carlos, Madrid, Spain 35 Hospital Universitario Central de Asturias, Oviedo, Spain 36 University ofMaryland School ofMedicine, Baltimore, MD, USA 37 Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain