Parkinson's disease is associated with clonal hematopoiesis with TET2 mutation.

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson's disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11-2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.

Clonal hematopoiesis with DNMT3A mutations is associated with multiple system atrophy.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular diseases and other disorders, possibly via inflammation. Recent research suggests a connection of CHIP with neurodegenerative disorders. OBJECTIVE: We aimed to investigate the association between multiple system atrophy (MSA) and CHIP. METHODS: We included 100 patients with MSA and 4457 controls. Targeted sequencing of peripheral blood DNA samples was performed, focusing on a panel of 25 genes commonly. LINKED TO CHIP: The prevalence of CHIP in patients with MSA was assessed against controls at variant allele frequency (VAF) thresholds of 1.5 % and 2.0 %. RESULTS: DNMT3A mutation rates were significantly higher in patients with MSA, with a VAF of 1.5 %, which remained significant after adjusting for age and sex (adjusted odds ratio, 1.848; 95 % CI, 1.024-3.335; p = 0.0416). CONCLUSION: Our results suggest an association between DNMT3A mutations and MSA.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

STUDY OBJECTIVES: Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. METHODS: This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. RESULTS: In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). CONCLUSIONS: Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.

Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson's disease.

The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.

Monoaminergic degeneration, cognition, and autonomic symptom trajectory in early Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) encompasses a range of non-motor symptoms attributed to deficits in various neurotransmitter systems. This study aimed to investigate the associations between cognitive and autonomic symptoms and the degeneration of brainstem monoaminergic nuclei, particularly the serotonergic and noradrenergic nuclei, in a prospective cohort of early PD patients. METHODS: Twenty-eight early PD patients (with an average disease duration of approximately three years) underwent baseline [18F]FP-CIT positron emission tomography (PET) scans, Montreal Cognitive Assessment (MoCA), and Composite Autonomic Symptom Scale-31 (COMPASS-31) evaluations, followed by repeat MoCA and COMPASS-31 assessments three years later. Regression models were utilized to analyze both cross-sectional and longitudinal changes in non-motor symptoms relative to baseline degeneration of the noradrenergic locus coeruleus (LC) and serotonergic raphe, normalized by striatal dopaminergic terminal loss. RESULTS: Baseline LC and raphe degeneration in early PD was cross-sectionally associated with poorer MoCA performances. Over the three-year follow-up, gastrointestinal symptoms exhibited progression, while cognitive scores remained stable. Profound baseline degeneration of the LC and raphe, relative to nigrostriatal terminal loss, were predictive of subsequent accelerated deterioration in gastrointestinal symptoms. CONCLUSION: Brainstem non-dopaminergic dysfunction in early PD is linked to cognitive dysfunction and predicts progression in gastrointestinal symptoms, offering potential indicators for worsening non-motor trajectories.

Evidence-based review on symptomatic management of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder with a significant impact on patients' quality of life, characterized by motor, behavioral, and cognitive impairments. This evidence-based review, conducted by the Korean Huntington Disease Society (KHDS) task force, systematically examines current pharmacological and non-pharmacological interventions for symptomatic management of HD. Following PRISMA guidelines, databases were searched for studies up to August 2022, focusing on 23 symptoms across four domains: motor, neuropsychological, cognition, and others. This review provides a comprehensive and systematic approach to the management of HD, highlighting the need for more high-quality clinical trials to develop robust evidence-based guidelines.

Symmetric and Profound Monoaminergic Degeneration in Parkinson's Disease with Premotor REM Sleep Behavior Disorder.

Background: Rapid eye movement sleep behavior disorder (RBD) may precede or follow motor symptoms in Parkinson's disease (PD). While over 70% of idiopathic RBD cases phenoconvert within a decade, a small subset develops PD after a more extended period or remains nonconverted. These heterogeneous manifestations of RBD in PD prompt subtype investigations. Premotor RBD may signify "body-first" PD with bottom-up, symmetric synucleinopathy propagation. Objective: Explore brainstem and nigrostriatal monoaminergic degeneration pattern differences based on premotor RBD presence and duration in de novo PD patients. Methods: In a cross-sectional analysis of de novo PD patients (n = 150) undergoing FP-CIT PET and RBD Single-Question Screen, the cohort was categorized into groups with and without premotor RBD (PDRBD +/-), with further classification of PDRBD + based on a 10-year duration of premotor RBD. Analysis of FP-CIT binding in the striatum and pons, striatal asymmetry, and striatum-to-pons ratios compared patterns of nigrostriatal and brainstem monoaminergic degeneration. Results: PDRBD + exhibited more severe and symmetrical striatal dopaminergic denervation compared to PDRBD-, with the difference in severity accentuated in the least-affected hemisphere. The PDRBD +<10Y subgroup displayed the most prominent striatal symmetry, supporting a more homogeneous "body-first" subtype. Pontine uptakes remained lower in PDRBD + even after adjusting for striatal uptake, suggesting early degeneration of pontine monoaminergic nuclei. Conclusions: Premotor RBD in PD is associated with severe, symmetrical nigrostriatal and brainstem monoaminergic degeneration, especially in cases with PD onset within 10 years of RBD. This supports the concept of a "widespread, bottom-up" pathophysiological mechanism associated with premotor RBD in PD.

The prevalence of non-troublesome dyskinesia in Parkinson's disease.

INTRODUCTION: Levodopa-induced dyskinesia is a common complication of long-term treatment of Parkinson's disease (PD), but its impact on daily activities is somewhat controversial. This study investigated the prevalence and severity of dyskinesia, particularly non-troublesome dyskinesia, to provide insights into its significance for long-term PD management. METHODS: We reviewed electronic medical records of 2571 PD patients, who had been followed up at Seoul National University Hospital and were seen between January 2016 and June 2017. Dyskinesia severity had been assessed during follow-up and was recorded with the highest score by considering its impact on functioning (0 = no dyskinesia, 1 = minimal with patient unaware, 2 = mild disability, 3 = moderate disability, 4 = severe disability). RESULTS: The prevalence of dyskinesia increased progressively with longer PD duration; 8.2% in the group with disease duration of 0-5 years, 40.7% for 6-10 years, 66.0% for 11-15 years, 74.6% for 16-20 years, and 83.2% for 21 years or more. The prevalence of dyskinesia scores ≥2 also increased with disease duration, with rates of 6.3% for 0-5 years, 31.9% for 6-10 years, 54.8% for 11-15 years, 62.9% for 16-20 years and 73.7% for 21 or more years. CONCLUSION: Despite the increasing prevalence and severity of dyskinesia with longer PD duration, the study found that less than non-troublesome dyskinesia remained at approximately 26.3% even after more than 21 years of disease duration. These findings suggest that dyskinesia may not be troublesome for many PD patients even in long-term.

Impaired cognitive flexibility and disrupted cognitive cerebellum in degenerative cerebellar ataxias.

There is a clinically unmet need for a neuropsychological tool that reflects the pathophysiology of cognitive dysfunction in cerebellar degeneration. We investigated cognitive flexibility in degenerative cerebellar ataxia patients and aim to identify the pathophysiological correlates of cognitive dysfunction in relation to cerebellar cognitive circuits. We prospectively enrolled degenerative cerebellar ataxia patients with age-matched healthy controls who underwent 3 T 3D and resting-state functional MRI. All 56 participants were evaluated with the Scale for Assessment and Rating of Ataxia and neuropsychological tests including the Wisconsin Card Sorting Test, Trail Making Test, Montreal Cognitive Assessment and Mini-Mental State Examination. From MRI scans, we analysed the correlation of whole-brain volume and cortico-cerebellar functional connectivity with the Wisconsin Card Sorting Test performances. A total of 52 participants (29 ataxia patients and 23 healthy controls) were enrolled in this study. The Wisconsin Card Sorting Test scores (total error percentage, perseverative error percentage, non-perseverative error percentage and categories completed), Trail Making Test A and Montreal Cognitive Assessment were significantly impaired in ataxia patients (P < 0.05) compared to age-matched healthy controls. The Wisconsin Card Sorting Test error scores showed a significant correlation with the ataxia score (P < 0.05) controlling for age and sex. In volumetric analysis, the cerebellar right crus I, II, VIIb and VIII atrophy correlated with non-perseverative error percentage in the ataxia group. In functional connectivity analysis, the connectivity between crus I, II and VIIb of the cerebellum and bilateral superior parietal and superior temporal gyrus was significantly altered in ataxia patients. The functional connectivity between left crus II and VIIb of the cerebellum and dorsolateral prefrontal and superior frontal/parietal cortices showed a positive correlation with perseverative error percentage. The connectivity between left crus VIIb and pontine nucleus/middle cerebellar peduncle showed a significant negative correlation with non-perseverative error percentage in the ataxia group. The impaired cognitive flexibility represented by the Wisconsin Card Sorting Test was significantly impaired in degenerative cerebellar ataxia patients and correlated with disease severity. The Wisconsin Card Sorting Test performance reflects hypoactivity of the cognitive cerebellum and disrupted cortico-cerebellar connectivity in non-demented patients with degenerative cerebellar ataxia.

Electroencephalographic spectro-spatial covariance patterns related to phenoconversion in isolated rapid eye movement sleep behavior disorder and their longitudinal trajectories in α-synucleinopathies.

STUDY OBJECTIVES: This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies. METHODS: We assessed 47 participants, including 35 patients with iRBD and 12 healthy controls (HC), through baseline eye-closed resting EEGs. Patients with iRBD underwent follow-up EEG assessments and 18 patients with iRBD converted (12 to Parkinson's disease (PD), 6 to dementia with Lewy bodies [DLB]) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined. RESULTS: At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve [AUC] = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman's rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters. CONCLUSIONS: Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

Aim: While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. Material and methods: This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. Results: The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). Conclusion: The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Brain olfactory-related atrophy in isolated rapid eye movement sleep behavior disorder.

OBJECTIVE: To investigate structural and functional connectivity changes in brain olfactory-related structures in a longitudinal prospective cohort of isolated REM sleep behavior disorder (iRBD) and their clinical correlations, longitudinal evolution, and predictive values for phenoconversion to overt synucleinopathies, especially Lewy body diseases. METHODS: The cohort included polysomnography-confirmed iRBD patients and controls. Participants underwent baseline assessments including olfactory tests, neuropsychological evaluations, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, 3T brain MRI, and 18 F-FP-CIT PET scans. Voxel-based morphometry (VBM) was performed to identify regions of atrophy in iRBD, and volumes of relevant olfactory-related regions of interest (ROI) were estimated. Subgroups of patients underwent repeated volumetric MRI and resting-state functional MRI (fMRI) scans after four years. RESULTS: A total of 51 iRBD patients were included, with 20 of them converting to synucleinopathy (mean time to conversion 3.08 years). Baseline VBM analysis revealed atrophy in the right olfactory cortex and gyrus rectus in iRBD. Subsequent ROI comparisons with controls showed atrophy in the amygdala. These olfactory-related atrophies tended to be associated with worse depression, anxiety, and urinary problems in iRBD. Amygdala 18 F-FP-CIT uptake tended to be reduced in iRBD patients with hyposmia (nonsignificant after multiple comparison correction) and correlated with urinary problems. Resting-state fMRI of 23 patients and 32 controls revealed multiple clusters with aberrant olfactory-related functional connectivity. Hypoconnectivity between the putamen and olfactory cortex was associated with mild parkinsonian signs in iRBD. Longitudinal analysis of volumetric volumetric MRI in 22 iRBD patients demonstrated four-year progression of olfactory-related atrophy. Cox regression analysis revealed that this atrophy significantly predicted phenoconversion. INTERPRETATION: Progressive atrophy of central olfactory structures may be a potential indicator of Lewy body disease progression in iRBD.

Diet quality and prodromal Parkinson's disease probability in isolated REM sleep behavior disorder.

INTRODUCTION: It is reported that a diet that lowers oxidative stress reduces the prodromal Parkinson's disease (pPD) probability as well as the risk of Parkinson's disease (PD). In this study, we evaluated whether the diet quality of patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) were associated with the pPD probability score, PD risk markers, or prodromal markers. METHODS: Polysomnography (PSG)-confirmed iRBD patients from the Neurology Department at Seoul National University Hospital were enrolled. We calculated the pPD probability using the "Web-based Medical Calculator for Prodromal Risk in Parkinsonism" Diet quality was assessed using the Recommended Food Score (RFS). RESULTS: We enrolled 101 patients with iRBD. The mean RFS score of patients with iRBD was 28.23 ± 9.29, which did not differ from the general population. Among patients with iRBD, the probability of pPD did not differ between the high and low RFS groups. In patients aged <70 years, although total RFS was not correlated with pPD probability (p = 0.529, Spearman rank correlation), legume consumption was negatively correlated with pPD probability (p = 0.032): furthermore, legume consumption was significantly higher in patients with fewer prodromal markers (p = 0.016). CONCLUSION: Diet quality assessed by RFS did not differ between the general population and patients with iRBD in Korea. Further studies are needed to confirm these protective effects of legume consumption on iRBD, which may have strong implications for the prevention and management of PD.

Inability to suppress head rotation during the saccade test as a clinical biomarker for cognitive dysfunction in Parkinson's disease.

BACKGROUND: There is a need for development of reliable and accessible clinical biomarker for detecting cognitive dysfunction in PD. This study aimed to investigate whether involuntary head rotation during the saccade test could serve as a potential biomarker for screening cognitive dysfunction in PD. METHODS: A total of 27 PD patients and nine age- and sex-matched healthy controls were prospectively enrolled in this study. A custom-designed gyroscope was attached to the forehead of each participant, and a saccade test consisting of 20 trials was conducted. The entire test was recorded on video, and two movement disorder experts independently rated the degree of head rotation, blinded to the patients' clinical information. The peak angular velocity of head rotation was derived from the gyroscope data. Participants underwent Montreal Cognitive Assessment (MoCA) as the cognitive evaluation. Correlation analysis was performed to assess the relationship between head rotation and MoCA scores. RESULTS: The mean peak angular velocity of head rotation significantly correlated with the MoCA scores (R = -0.52, p = 0.0023) including age, sex, disease duration, and education duration as cofactors. The optimal peak angular velocity thresholds for head rotation, which aligned with the manual ratings, were determined to be 5°/s and 10°/s for raters 1 and 2, respectively. The MoCA scores exhibited significant correlations with the number of head rotations, using both the 5°/s (R = -0.36, p = 0.042) and 10°/s (R = -0.49, p = 0.0048) thresholds. Furthermore, the mean angular velocity of the head demonstrated a 100% positive predictive value and specificity for the detection of cognitive impairment (MoCA < 26), based on the cut-offs of 5°/s and 10°/s. CONCLUSION: Inability to suppress head rotation during saccades may serve as a potential clinical biomarker for screening cognitive dysfunction in PD.

Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder: a prospective cohort study.

BACKGROUND: The isolated rapid-eye-movement sleep behavior disorder (iRBD) is a prodromal condition of Lewy body disease including Parkinson's disease and dementia with Lewy bodies (DLB). We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD. METHODS: We enrolled 22 DLB patients, 44 healthy controls, and 50 video polysomnography-proven iRBD patients. Participants underwent 3-T magnetic resonance imaging (MRI) and clinical/neuropsychological evaluations. We characterized DLB-related whole-brain cortical thickness spatial covariance pattern (DLB-pattern) using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls. We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients. With repeated MRI data during the follow-up in our prospective iRBD cohort, we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia. Finally, we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort. RESULTS: The DLB-pattern was characterized by thinning of the temporal, orbitofrontal, and insular cortices and relative preservation of the precentral and inferior parietal cortices. The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction (Trail Making Test-A and B: R = - 0.55, P = 0.024 and R = - 0.56, P = 0.036, respectively) as well as visuospatial impairment (Rey-figure copy test: R = - 0.54, P = 0.0047). The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters (Pearson's correlation, R = 0.74, P = 6.8 × 10-4) but no significant change in parkinsonism-first phenoconverters (R = 0.0063, P = 0.98). The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33 [1.16-74.12]. The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2% accuracy. CONCLUSION: Cortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population. Replication studies would further validate the utility of this imaging marker in iRBD.