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Original research
Association of choroid plexus volume with motor symptoms and dopaminergic degeneration in Parkinson’s disease
  1. Seong Ho Jeong1,2,
  2. Chae Jung Park3,
  3. Hyun-Jae Jeong4,
  4. Mun Kyung Sunwoo5,
  5. Sung Soo Ahn6,
  6. Seung-Koo Lee6,
  7. Phil Hyu Lee2,
  8. Yun Joong Kim2,7,8,
  9. Young Ho Sohn2,
  10. Seok Jong Chung2,7,8
  1. 1 Department of Neurology, Inje University Sanggye Paik Hospital, Seoul, Korea (the Republic of)
  2. 2 Department of Neurology, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  3. 3 Department of Radiology, Yongin Severance Hospital, Yonsei University Health System, Yongin, Geyonggi-do, Korea (the Republic of)
  4. 4 Research Institute of Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  5. 5 Department of Neurology, Daejin Medical Foundation Bundang Jesaeng Hospital, Seongnam, Gyeonggi-do, Korea (the Republic of)
  6. 6 Department of Radiology, Severance Hospital, Research Institute of Radiological Science and Centre for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  7. 7 Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, Gyeonggi-do, Korea (the Republic of)
  8. 8 YONSEI BEYOND LAB, Yongin, Gyeonggi-do, South Korea
  1. Correspondence to Dr Seok Jong Chung, Department of Neurology, Yongin Severance Hospital, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Korea (the Republic of); sjchung{at}yuhs.ac

Abstract

Background The choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. This study aimed to investigate the association between CP volume (CPV), nigrostriatal dopaminergic degeneration and motor outcomes in Parkinson’s disease (PD).

Methods We retrospectively searched drug-naïve patients with early-stage PD who underwent dopamine transporter (DAT) scanning and MRI. Automatic CP segmentation was performed, and the CPV was calculated. The relationship between CPV, DAT availability and Unified PD Rating Scale Part III (UPDRS-III) scores was assessed using multivariate linear regression. We performed longitudinal analyses to assess motor outcomes according to CPV.

Results CPV was negatively associated with DAT availability in each striatal subregion (anterior caudate, β=−0.134, p=0.012; posterior caudate, β=−0.162, p=0.002; anterior putamen, β=−0.133, p=0.024; posterior putamen, β=−0.125, p=0.039; ventral putamen, β=−0.125, p=0.035), except for the ventral striatum. CPV was positively associated with the UPDRS-III score even after adjusting for DAT availability in the posterior putamen (β=0.121; p=0.035). A larger CPV was associated with the future development of freezing of gait in the Cox regression model (HR 1.539, p=0.027) and a more rapid increase in dopaminergic medication in the linear mixed model (CPV×time, p=0.037), but was not associated with the risk of developing levodopa-induced dyskinesia or wearing off.

Conclusion These findings suggest that CPV has the potential to serve as a biomarker for baseline and longitudinal motor disabilities in PD.

  • PARKINSON'S DISEASE
  • MRI
  • PET, FUNCTIONAL IMAGING

Data availability statement

Data generated or analysed during the study are available from the corresponding author by request.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • The choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. The function of the CP in neurodegenerative disorders is garnering interest owing to its relevance to the glymphatic drainage system.

WHAT THIS STUDY ADDS

  • This study demonstrated that CP enlargement was associated with a severe decrease in striatal dopamine transporter availability, severe baseline motor deficits, a high risk of developing freezing of gait and a rapid increase in the dose of dopaminergic medication in patients with Parkinson’s disease (PD).

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Our findings imply that CP volume, which can be easily and automatically obtained from MRI, has the potential to serve as a biomarker for baseline and longitudinal motor disabilities in patients with PD.

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterised by the progressive loss of nigrostriatal dopaminergic neurons. The neuropathological hallmarks of PD are Lewy bodies and Lewy neurites, which are the results of misfolded α-synuclein accumulation.1 Along with Alzheimer’s disease (AD), which is also caused by the aggregation of pathological proteins (ie, β-amyloid and tau),2 recent studies have shown that dysfunction of the glymphatic system—waste clearance system in brain—leads to accumulation of protein aggregates and is closely associated with these neurodegenerative disorders.3

The choroid plexus (CP) is a highly vascularised structure in the ventricles that is responsible for the production of cerebrospinal fluid (CSF). The function of the CP in neurodegenerative disorders is garnering interest owing to its relevance to the glymphatic drainage system. Postmortem studies have reported that morphological changes of the CP were observed in AD,4 5 and a recent in vivo study showed that CP volume (CPV) was greater in patients with more severe stages of AD.6 Another study showed that there were negative associations between CPV and CSF protein levels (total-tau and phosphorylated-tau) in patients with AD, suggesting the possible role of CP in the clearance of CSF proteins and providing evidence for CP dysfunction in AD.7 However, few studies have investigated the clinical relevance of CP dysfunction in populations with PD. Given that several previous studies have shown that glymphatic function affects nigrostriatal dopaminergic degeneration and motor prognosis in patients with PD,8–10 we investigated whether CPV at initial assessment was associated with baseline parkinsonian motor deficits, striatal dopamine transporter (DAT) availability and clinical parameters of motor prognosis, including longitudinal changes in doses of dopaminergic medications and the development of levodopa-induced dyskinesia (LID), wearing off and freezing of gait (FOG), in patients with PD.

Methods

Participants

In this retrospective study, a total of 660 patients with newly diagnosed PD who first visited the movement disorders outpatient clinic at the Yonsei University Severance Hospital between April 2009 and September 2015 were searched. The exclusion criteria were as follows: (1) patients without available three-dimensional (3D) T1-weighted images (n=259); (2) patients without baseline Unified PD Rating Scale Part III (UPDRS-III) scores (n=68); and (3) preprocessing error before automatic CP segmentation (n=11). Therefore, 322 patients were finally enrolled in this study (figure 1).

Figure 1

Flow diagram of the study participants. 3D, three-dimensional; CP, choroid plexus; PD, Parkinson’s disease; UPDRS-III, Unified PD Rating Scale Part III.

PD was diagnosed according to the clinical diagnostic criteria of the UK PD Society Brain Bank. All patients underwent DAT imaging using N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (18F-FP-CIT PET), which revealed a decrease in DAT availability in the posterior putamen on all the patients. In addition, they underwent MRI including 3D T1-weighted MRI at baseline. Parkinsonism was evaluated at the initial visit using the UPDRS-III. Patients with PD were classified into three clinical subtypes based on UPDRS-II and III: tremor dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate.11

Quantitative analyses of 18F-FP-CIT PET

The detailed PET acquisition and preprocessing process is described in the online supplemental method 1.12 The striatum was divided into the anterior caudate, posterior caudate, anterior putamen, posterior putamen, ventral putamen and ventral striatum. DAT availability of each subregion was defined as (mean standardised uptake value of the striatal subregion volume of interests (VOIs)–mean standardised uptake value of the occipital VOI)/(mean standardised uptake of the occipital VOI).

Supplemental material

MRI acquisition and analysis

The detailed MRI acquisition parameters are described in the online supplemental method 2. Automated segmentation of CP in the lateral ventricles was performed according to the Gaussian mixture model (GMM) segmentation method, as previously described (figure 2).13 This method proved its superior accuracy compared with Freesurfer, which has been conventionally used in prior studies of automatic CP segmentation.6 7 14 The detailed process of CP segmentation is presented in the online supplemental method 3. In a subset of 20 patients, we additionally obtained manual segmentations of the CPV to assess the intermethod reliability. One neuroradiologist (CJP with 5 years of experience) manually segmented the CP in the lateral ventricle on the 3D T1-weighted volumetric images using 3D slicer V.5.0.3 (https://www.slicer.org). Intracranial volume (ICV), CPV, lateral ventricle volume (LVV), grey matter volume (GMV), white matter hyperintensity volume (WMHV) and hippocampal volume were obtained. All final automatic segmentation results were checked and approved without any manual correction by a single neuroimaging researcher (CJP). The regional volume was expressed as the ratio of the regional volume to the total ICV (ratio of ICV×103).

Figure 2

Gaussian mixture model-based CP segmentation. CP volume is segmented from high-resolution T1-weighted MRI using the pipeline for Gaussian mixture model segmentation described in the online supplemental methods. 3D, three-dimensional; CP, choroid plexus.

To perform a sensitivity analysis, we classified patients into three tertiles using the CPV ratio to the ICV: low-tertile group (CPV <1.1; n=107), middle-tertile group (1.1≤CPV<1.5; n=108) and high-tertile group (CPV ≥1.5; n=107).

Assessment of the development of LID, wearing off and FOG

The participants visited our outpatient clinic every 3–6 months, and two movement disorder experts (YHS and PHL) carefully assessed the presence of LID, wearing off and FOG through a history obtained from patients and caregivers or by direct neurological examination at every visit.15 16 The date on which the patients with PD or their caregivers reported that LID occurred or the date on which LID was first observed in the clinic was regarded as the date of occurrence of LID. The onset of wearing off was defined as the time point when patients first complained of end-of-dose deterioration or when we first decided to increase the dosing schedule of levodopa from three times to four times a day. Nocturnal or early morning off symptoms were not considered proof of wearing off. FOG was defined as an unintentional and temporary phenomenon in which the feet fail to progress forward, despite the intention to walk, and various subtypes have been identified: hesitation at the initiation of walking, freezing on turning, freezing in restricted areas, destination freezing and open-space hesitation in the absence of stimuli likely to result in FOG. Two movement disorder specialists specifically asked the patients about the characteristic sensation of the feet becoming ‘glued to the floor’ at every visit and determined FOG based on inspection of the patients’ gait at the outpatient clinic.

Longitudinal changes in dopaminergic medication doses

A subset of participants (n=284) visited the outpatient clinic for at least 2 years. The doses of their dopaminergic medications were adjusted to effectively control motor symptoms by two movement disorder experts (YHS and PHL) according to the patients’ responses. We calculated the levodopa-equivalent doses (LEDs) of dopaminergic medication using the following formula based on a previously reported method.17 18

Statistical analysis

We performed a partial correlation analysis to identify the relationship between CPV and other imaging parameters after adjusting for age at symptom onset, sex, disease duration and body mass index (BMI). To identify the independent effect of CPV on parkinsonian motor symptoms assessed using UPDRS-III scores at initial visit, multivariate linear regression analysis was performed after adjusting for age at symptom onset, sex, symptom duration, DAT availability in the posterior putamen, BMI and WMHV. Multivariate linear regression analysis for DAT availability in each striatal subregion was performed to explore the effect of CPV on baseline presynaptic dopaminergic degeneration after adjusting for age at symptom onset, sex, symptom duration, BMI and WMHV. The false discovery rate (FDR) method was used to correct multiple tests for the six striatal subregions.

In addition, mediation analyses were performed to evaluate the complex relationship between CPV, DAT availability in the posterior putamen and UPDRS-III score. Age at symptom onset, sex, disease duration, BMI and WMHV were entered as covariates. We used a bootstrapping method with 1000 resamples to derive the 95% CIs and SEs using the ‘lavaan’ package for the R program.19

Cox regression models were used to estimate the HRs and 95% CIs for the development of LID, wearing off or FOG according to CPV, while adjusting for age at symptom onset, sex, disease duration, BMI, motor subtype (TD vs PIGD/indeterminate type), DAT availability in the posterior putamen, LED (ie, LED at the time of LID, wearing off, FOG onset or at the last visit to the outpatient clinic in patients without LID, wearing off or FOG) and WMHV. A linear mixed model was used to assess the effect of CPV on the rate of longitudinal changes in LED for 2 years. If the physicians cannot escalate the dose of dopaminergic medication due to intolerable dyskinesia or adverse effects despite worsening parkinsonism, LEDs until this point were included in the longitudinal LED analysis. We regarded time as a continuous variable. Participants were included as random effects, and age at symptom onset, sex, disease duration, BMI, motor subtype, DAT availability in the posterior putamen and WMHV were included as fixed-effect terms. The effect of CPV on the longitudinal changes in the LED was tested using a CPV×time interaction term.

Sensitivity analysis was performed on all statistical models using tertile groups as a variable instead of CPV to confirm the robustness of the results of this study. Statistical analyses were performed using the R software (V.4.0, http://www.r-project.org). Results with a two-tailed p value of <0.05 were considered statistically significant.

Result

Demographic and clinical characteristics

The demographic and clinical characteristics of the 322 patients with PD are shown in table 1. The average age at symptom onset was 64.14±9.72 years and 52.8% of the patients were female. The average symptom duration prior to diagnosis was 17.13±15.34 months and the baseline UPDRS-III score was 23.26±10.50. Of patients with PD, 50.0% had PIGD or indeterminate subtypes. The demographic and clinical characteristics using a tertile-based approach are shown in online supplemental table 1.

Table 1

Demographic characteristics and dopamine transporter (DAT) availability in patients with Parkinson’s disease

Relationship between CPV and other parameters

The GMM segmentation of the CPV demonstrated good reliability (intraclass correlation coefficient=0.793, 95% CI (0.476 to 0.918), p<0.001) compared with the manual segmentation of the CPV as a reference standard. Partial correlation analyses showed that the CPV was significantly associated with LVV (r=0.60, p<0.001), GMV (r=0.27, p<0.001), WMHV (r=0.20, p<0.001) and hippocampal volume (r=0.20, p<0.001).

Effect of CPV on parkinsonian motor symptoms and DAT availability in each striatal subregion

Multivariate linear regression analysis showed that CPV was significantly associated with UPDRS-III score (β=0.121, p=0.035) after adjusting for age at symptom onset, sex, disease duration, DAT availability in the posterior putamen, BMI and WMHV (online supplemental table 2). In terms of DAT availability, simple correlation analyses showed that CPV was significantly correlated with DAT availability in each striatal subregion (figure 3A). Similarly, the high-tertile group showed more severely decreased DAT availability in all striatal subregions than the low-tertile group using a tertile-based approach (figure 3B). In multivariate linear regression analyses after adjusting for potential confounders, CPV was still significantly associated with DAT availability in the anterior caudate (β=−0.134, FDR-corrected p=0.035), posterior caudate (β=−0.162, FDR-corrected p=0.015), anterior putamen (β=−0.133, FDR-corrected p=0.046), posterior putamen (β=−0.125, FDR-corrected p=0.046) and ventral putamen (β=−0.125, FDR-corrected p=0.046), but not with DAT availability in the ventral striatum (β=−0.090, FDR-corrected p=0.117; table 2). A tertile-based approach yielded similar results (online supplemental table 3). Because CPV affected both the UPDRS-III score and DAT availability in the posterior putamen with a significant effect of DAT availability in the posterior putamen on the UPDRS-III score, we further investigated the complex relationship between these three variables using mediation analysis. Mediation analysis showed that CPV affected both directly (β=2.137, bootstrapping SE (BootSE)=1.001, p=0.033) and indirectly, via DAT availability in the posterior putamen (β=0.535, BootSE=0.212, p=0.012), the UPDRS-III score, while the direct effect was responsible for most of the total effect (80.0%; online supplemental table 4 and figure 4).

Figure 3

(A) Correlation analysis between CPV and DAT availability. DAT availability in each striatal subregion was negatively correlated with CPV. (B) Rain-cloud plots of DAT availability in the striatal subregions according to the tertile group of CPV. DAT availability in each striatal subregion was lower in the high-tertile group than in low-tertile group. *Uncorrected p<0.05; **uncorrected p<0.01; ***uncorrected p<0.001; ****uncorrected p<0.0001. CPV, choroid plexus volume; DAT, dopamine transporter; ns, not significant.

Figure 4

Mediation analysis. The CPV and DAT availability in the posterior putamen were entered as a predictor and mediator, respectively. Mediation analysis was performed while controlling for the effects of age at symptom onset, sex, disease duration, BMI and WMHV. BMI, body mass index; BootSE, bootstrapping SE; CPV, choroid plexus volume; DAT, dopamine transporter; UPDRS-III, Unified Parkinson’s Disease Rating Scale Part III; WMHV, white matter hyperintensity volume.

Table 2

Multivariate linear regression analysis of dopamine transporter availability in each striatal subgroup

Effect of CPV on the development of LID, wearing off and FOG

During the follow-up period (5.42±2.50 years), LID, wearing off and FOG developed in 73 (22.7%), 79 (24.5%) and 68 (21.1%) of patients with PD, respectively. The Cox regression model showed that baseline CPV did not significantly affect the development of LID (HR=1.202, 95% CI 0.782 to 1.849, p=0.402) and wearing off (HR=1.278, 95% CI 0.865 to 1.887, p=0.218), after adjusting for covariates. However, CPV was a significant predictor of the future development of FOG (HR=1.539, 95% CI 1.051 to 2.251, p=0.027; table 3). Using a tertile-based approach, the Cox regression model showed that the risk of FOG development during the follow-up period was significantly higher in the high-tertile group than in the low-tertile group (HR=2.172; 95% CI 1.156 to 4.081; p=0.016; online supplemental table 5).

Table 3

Cox regression models for prediction of the development of LID, wearing off and FOG

Effect of CPV on longitudinal changes in LED

The CPV×time interaction term in the linear mixed model was statistically significant (β=19.86, SE=9.53, p=0.037), indicating that patients with a greater CPV showed a more rapid increase in LED (table 4). Sensitivity analysis using a tertile-based approach showed that the high-tertile group required higher doses of dopaminergic medications than the middle-tertile and low-tertile groups (online supplemental table 6).

Table 4

Longitudinal changes of levodopa-equivalent doses (LEDs) according to CPV for 2 years

Discussion

In this study, we investigated the relationship between CPV, baseline parkinsonian motor symptoms, nigrostriatal dopaminergic degeneration and motor prognosis in patients with PD. The major findings were as follows: (1) a larger CPV was associated with higher baseline UPDRS-III scores and more severely decreased striatal DAT availability; (2) although the direct and indirect effects via mediation of DAT availability in the posterior putamen of the CPV on the UPDRS-III score were both significant, the direct effect accounted for the majority of the total effect (80.0%); (3) a larger CPV was associated with a higher risk of developing FOG, while no association was found between the CPV and the development of LID or wearing off; and (4) a larger CPV was associated with more rapid increases in dopaminergic medications over time. These findings suggest that CPV is associated with striatal DAT availability and parkinsonian motor deficits at initial assessment. Furthermore, CP enlargement may be associated with poor outcomes with respect to the progression of motor disabilities in patients with PD.

Since the main function of CP is to control the production and composition of CSF and most molecules in the brain are cleared from the CSF, several previous studies have proposed that CP may be a candidate for therapeutic target in neurological diseases.20 21 Although the clinical relevance of volume changes in CP in neurological disorders remains unclear, a recent clinical study showed that CPV is negatively associated with the level of cognitive performance in the AD continuum.6 In addition, several preclinical studies have shown that CP function affects β-amyloid clearance in an AD mouse model.22 23 Meanwhile, the clinical relevance of CP dysfunction in patients with PD is not yet fully understood.

In this study, multivariate linear regression analyses demonstrated that DAT availability in each striatal subregion, except for the ventral striatum, was negatively associated with CPV. This is the first study to investigate the relationship between CPV and nigrostriatal presynaptic dopaminergic denervation in patients with PD. Considering that CP is closely related to glymphatic function,24 previous studies that have explored the role of glymphatic dysfunction in the pathogenesis of PD may provide possible explanations. Several preclinical and clinical studies demonstrated that glymphatic dysfunction plays a significant role in PD.10 25 26 In addition, our previous study showed that a high number of enlarged perivascular space in the basal ganglia, which is regarded as one of the imaging markers of glymphatic dysfunction, was associated with more severely decreased striatal DAT availability.8 Taken together, the result of the present study also suggests that CP enlargement may reflect dysfunction of waste clearance and have a detrimental effect on neurodegenerative processes in patients with PD.

Furthermore, we investigated the effect of CPV on baseline parkinsonian motor deficits, showing that CPV was positively associated with the UPDRS-III score. Further mediation analysis showed that CPV affected the UPDRS-III scores both directly and indirectly via DAT availability in the posterior putamen after adjusting for possible confounding factors. Among the direct and indirect effects, the direct effect was most of the total effect. Although nigrostriatal dopaminergic denervation at the presynaptic level is the major pathophysiology of parkinsonian motor deficits, the extra-nigrostriatal pathway also contributes to parkinsonism.12 27 The result of mediation analysis suggests that a large CPV may be related to a greater burden of extra-nigrostriatal neurodegeneration (major effect) as well as more severe nigrostriatal dopaminergic degeneration (minor effect), which subsequently leads to parkinsonian motor signs. Glymphatic dysfunction is not a specific pathomechanism for synucleinopathies but is associated with neurodegenerative conditions (ie, neuroinflammation or aggregation of other pathological proteins such as β-amyloid or tau),28–30 and the direct association between CPV and UPDRS-III score is plausible.

In terms of motor prognosis, the CPV was not associated with the future risk of LID or wearing off, whereas a larger CPV was associated with a higher risk of the development of FOG. This finding is in accordance with our previous study showing that a high number of enlarged perivascular space in the basal ganglia was an imaging marker for the future development of FOG in patients with PD.8 Taking the pathogenesis of LID, wearing off and FOG into consideration, the present study highlights that CPV may reflect post-synaptic neurodegeneration caused by neuroinflammation or toxic protein aggregation28 29 rather than presynaptic dopamine depletion. Furthermore, a larger CPV was associated with a more rapid increase in dopaminergic medication use. A sensitivity analysis using a tertile-based approach also obtained similar results, showing that the high-tertile group showed faster increases in LED than the low-tertile group. Taken together, these findings suggest that the baseline CPV is also associated with the progression rate of motor disability in patients with PD.

The accurate segmentation of CP from high-resolution structural MRI is a prerequisite for investigating the clinical relevance of CP. To date, manual segmentation has been the gold standard for CP segmentation, and using contrast-enhanced images enables better visualisation of CP than using non-contrast images as the fenestrated endothelium in CP allows contrast to accumulate in the interstitium, while the CP–CSF barrier precludes contrast from leaking into the CSF.31 However, contrast agents are not routinely used in all patients in the clinical setting, while non-contrast high-resolution 3D T1-weighted images are usually included in the baseline MRI scans. Furthermore, as manual segmentation is a time-consuming and labour-intensive procedure, investigation of CP in a large number of patients with manual segmentation is not practical. Therefore, several studies have performed automatic CP segmentation using non-contrast 3D T1-weighted with Freesurfer software.6 7 14 In addition, a lightweight algorithm using GMM to segment CP within lateral ventricles has been recently proposed,13 as GMM does not require manual labelling for training and can generalise more robustly to unseen data by capturing idiosyncrasies present in CP without imposing a group-averaged constraint compared with Freesurfer.32 On the basis of these findings regarding GMM, we applied GMM-based automatic CP segmentation for more accurate results in this study. We observed good reliability between the GMM-based automatic segmentation and manual segmentation in patients with PD. Therefore, we believe that the GMM approach may be a reliable and accurate method for automatic CP segmentation and should be validated in the future in patients with variable neurodegenerative disease entities.

Our study had some limitations. First, because of the retrospective nature of this study, causal relationships should be demonstrated in other longitudinal comparative studies using sequential UPDRS-III scores, brain MRI and DAT imaging. Second, we defined LID, wearing off or FOG when clinicians detected signs or symptoms, which may limit the generalisation of the results due to the lack of quantitative and objective methodology. Third, since global disability in patients with PD is complexly influenced by motor and non-motor symptoms,33 34 the rate of increase in LED may not accurately reflect the progression of PD. Also, longitudinal changes of striatal DAT availability or parkinsonian motor symptoms assessed using the UPDRS-III or Movement Disorder Society-Sponsored Revision of the -UPDRS-III would reflect PD progression more appropriately. Future studies are needed to replicate the association between CPV and longitudinal motor outcomes in PD. Finally, because this retrospective study was conducted in a single centre of South Korea, the generalisation should be cautiously interpreted and the results of this study should be replicated in other studies.

In conclusion, our study demonstrated that CP enlargement was associated with a severe decrease in striatal DAT availability, severe baseline motor deficits, a high risk of developing FOG and a rapid increase in the dose of dopaminergic medication in patients with PD. These findings suggest that CPV, which can be easily and automatically rated on brain MRI, has the potential to serve as a biomarker for baseline and longitudinal progression of motor disability in patients with PD.

Data availability statement

Data generated or analysed during the study are available from the corresponding author by request.

Ethics statements

Patient consent for publication

Ethics approval

This study was approved by the institutional review board of Yonsei University College of Medicine (no. 4–2014-0637), and the requirement for informed consent was waived due to the retrospective nature of the study.

References

Footnotes

  • SHJ and CJP are joint first authors.

  • Contributors SJC takes full responsibility for the overall content as the guarantor. SHJ drafted the structure of the present work, took care of data analysis, drafted the first version of the work and revised the following versions critically for important intellectual content. CJP and SJC contributed to drafting the structure of the present work and revised the first version of the work critically for important intellectual content. All authors had full access to all the data in the study, substantially contributed to the interpretation of data for the present work, revised the work critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SHJ, CJP and SJC accept full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A1A01059678). Also, this research was supported by a grant from the Korea Health Technology R&D Project through the Korean Healthy Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI22C0224). This research was supported by the faculty research grants of Yonsei University College of Medicine (6-2020-0157).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.