Glial fibrillary acidic protein (GFAP) has been suggested as a biomarker for reactive astrogliosis. We measured the levels of plasma GFAP by Simoa in 60 patients with PD with normal cognition, 63 with mild cognitive impairment (PD-MCI), 24 with dementia (PDD) and 15 healthy controls. A subgroup of patients with PD-MCI (n = 31) was followed up for 4.1 ± 2.3 years. Compared with healthy controls, plasma GFAP levels were elevated in patients with PDD (adjusted P < 0.001) and PD-MCI (adjusted P = 0.013) and were negatively correlated with the Mini Mental State Examination (MMSE) score in PD participants. Plasma GFAP predicted MCI-to-dementia conversion with an AUC of 0.90, higher than NfL, Tau and pTau181. Our results support that plasma GFAP has potential value for distinguishing patients with PDD, and predicting MCI-to-dementia conversion in PD.

A new Parkinson’s disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PD^pRBD–, representing the brain-first subtype), PD patients with possible premotor RBD (PD^pRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.

Background: Quality of life (QoL) was worse in Parkinson’s disease patients with mild cognitive impairment (PD-MCI) or dementia (PDD) than PD patients with normal cognition (PD-NC). The aim of this study was to investigate and compare the potential heterogeneous determinants of QoL in PD patients with different cognitive statuses. Methods: We recruited 600 PD patients, including 185 PD-NC patients, 336 PD-MCI patients and 79 PDD patients, in this cross-sectional study. All patients completed the QoL assessment by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), as well as clinical evaluations and neuropsychological tests. The determinants of the QoL were analyzed by multiple stepwise regression analysis. Results: QoL was more impaired across the three groups (PD-NC < PD-MCI < PDD). The Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score, Geriatric Depression Rating Scale (GDS) score and daily levodopa equivalent dose (LED) were independent variables of PDQ-39 in PD-NC patients. The GDS score, disease duration, UPDRS-III score, Epworth Sleepiness Score (ESS) and sex were independent variables of PDQ-39 in PD-MCI patients. The GDS score and disease duration were independent variables of PDQ-39 in PDD patients. Conclusion: The determinants of QoL in PD-NC, PD-MCI and PDD patients were heterogeneous. Motor function was considered to be the most crucial determinant for QoL in PD-NC, while depression was indicated to be the most vital determinant for PD-MCI and PDD. For QoL improvement, clinicians might need to focus more on motor function in PD-NC patients and on depression in PD-MCI and PDD patients.

Objective: Little is known about the disease progression of Parkinson's disease patients with subjective cognitive complaint (PD‐SCC). This longitudinal cohort study aims to compare the progression of clinical features and quality of life (QoL) in PD patients with normal cognition (NC), SCC, and mild cognitive impairment (MCI).Methods: A total of 383 PD patients were enrolled, including 189 PD‐NC patients, 59 PD‐SCC patients, and 135 PD‐MCI patients, with 1–7 years of follow‐up. Linear mixed models were applied to evaluate longitudinal changes in motor symptoms, nonmotor features (cognitive impairment, depression, and excessive daytime sleepiness), and QoL in PD.Results: At baseline, PD‐SCC patients had lower Beck Depression Inventory (BDI) scores and Parkinson's Disease Questionnaire‐39 (PDQ‐39) scores than PD‐NC patients (all p < 0.05). Longitudinal analyses revealed that the PD‐SCC group exhibited faster progression in terms of BDI scores (p = 0.042) and PDQ‐39 scores (p = 0.035) than the PD‐NC group. The PD‐MCI group exhibited faster progression rates in the Epworth Sleepiness Scale scores (p = 0.001) and PDQ‐39 scores (p = 0.005) than the PD‐NC group. In addition, the PD‐SCC group exhibited a greater reduction in attention (Trail Making Test Part A, p = 0.047) and executive function (Stroop Color‐Word Test, p = 0.037) than the PD‐NC group.Interpretation: PD‐SCC patients exhibited faster deterioration of depression and QoL than PD‐NC patients, and SCC may be an indicator of initial attention and executive function decline in PD. Our findings provided a more accurate prognosis in PD‐SCC patients.

Rapid eye movement sleep behavior disorder (RBD) is increasingly recognized in patients with tauopathies, but its significance and underpinnings remain unclear. To address this gap, we investigated the prevalence of self-reported RBD in patients with progressive supranuclear palsy (PSP) and explored its clinical and imaging correlates using ¹⁸F-florzolotau PET imaging. We consecutively enrolled patients meeting the 2017 Movement Disorder Society clinical criteria for PSP at a Chinese tertiary hospital between May 2019 and March 2022. Patients underwent comprehensive clinical assessments and ¹⁸F-florzolotau PET to investigate tau deposition patterns. The presence of self-reported RBD was identified using the RBD Single-Question Screen, while its frequency was retrospectively collected from medical history. We examined 148 patients recruited in the ongoing Progressive Supranuclear Palsy Neuroimage Initiative cohort. Self-reported RBD was identified in 18.2% of the participants (27/148). Patients with PSP-Richardson syndrome and PSP-parkinsonism reported the highest frequencies of self-reported RBD (21.7% and 18.5%, respectively), compared with PSP-progressive gait freezing (9.7%). While age and sex were similar in patients with and without self-reported RBD, the former group exhibited greater disease severity, as indicated by higher PSP Rating Scale (PSPrs) scores (38.0 vs 27.0, effect size = 0.256, p = 0.002). Furthermore, patients with RBD had significantly higher ¹⁸F-florzolotau binding in the locus coeruleus (LC) (1.50 vs 1.38, effect size = 0.231, p = 0.003), which remained significant after false discovery rate correction (p = 0.042). The frequency of RBD was found to be correlated with tau pathology in the LC (n = 8, r = 0.752, p = 0.002). Notably, the presence of self-reported RBD symptoms mediated the relationship between LC tau pathology and PSPrs total scores (proportion-mediated = 2.09%, 95% CI 0.01%-10.00%, p = 0.044). Approximately one-fifth of patients with PSP reported RBD and exhibited more severe motor and nonmotor symptoms. The elevated ¹⁸F-florzolotau binding in the LC and its association with the presence of RBD symptoms underscore the critical role of tau pathology in disrupting sleep-regulating neural circuits. Future studies with larger sample sizes should incorporate polysomnography in patients with PSP with self-reported RBD to further elucidate this relationship.