"NU21-04-00535"
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Early identification of cognitive decline (CD) in de novo Parkinson's disease (PD) is crucial for choosing appropriate therapies and recruiting for clinical trials. However, existing prognostic models lack flexibility, scalability and require costly instrumentation. This study explores the utility of standard clinical questionnaires and criteria to predict CD in de novo PD. A total of 186 patients from the Parkinson Progression Markers Initiative (PPMI) and 48 patients from the Biomarkers of Parkinson's Disease project (BIO-PD) underwent clinical interviews, comprehensive tests, and questionnaires. A model based only on age of disease onset, history of stroke, history of fainting, and vocalization during dreams predicted CD in 2 and 4-year horizons with an area under curve (AUC) of 70% ± 10% standard deviation (cross-validated PPMI), 79% (overall PPMI), and 78% (validation in BIO-PD). This approach enables rapid preliminary screening using just four simple questions, achieving predictive accuracy comparable to instrumentation-based methods while reducing assessment time.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: The impact of dopaminergic medication on language in Parkinson's disease (PD) remains poorly understood. This observational, naturalistic study aimed to investigate the effects of long-term dopaminergic therapy on language performance in patients with de-novo PD based on a high-level linguistic analysis of natural spontaneous discourse. METHODS: A fairy-tale narration was recorded at baseline and a 12-month follow-up. The speech samples were automatically analyzed using six representative lexical and syntactic features based on automatic speech recognition and natural language processing. RESULTS: We enrolled 109 de-novo PD patients compared to 68 healthy controls. All subjects completed the 12-month follow-up; 92 PD patients were on stable dopaminergic medication (PD-treated), while 17 PD patients remained without medication (PD-untreated). At baseline, the PD-treated group exhibited abnormalities in syntactic domains, particularly in sentence length (p = 0.018) and sentence development (p = 0.042) compared to healthy controls. After 12 months of dopaminergic therapy, PD-treated showed improvements in the syntactic domain, including sentence length (p = 0.012) and sentence development (p = 0.030). Of all PD-treated patients, 37 were on monotherapy with dopamine agonists and manifested improvement in sentence length (p = 0.048), while 32 were on monotherapy with levodopa and had no language amelioration. No changes in language parameters over time were seen in both the PD-untreated group and healthy controls. DISCUSSION: Initiation of dopaminergic therapy improved high-language syntactic deficits in de-novo PD, confirming the role of dopamine in cognitive-linguistic processing. Automated linguistic analysis of spontaneous speech via natural language processing can assist in improving the prediction and management of language deficits in PD.
- MeSH
- agonisté dopaminu * terapeutické užití MeSH
- antiparkinsonika * terapeutické užití MeSH
- dopaminové látky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- Parkinsonova nemoc * farmakoterapie komplikace MeSH
- řeč * účinky léků MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a potential non-invasive marker of glymphatic function that typically relies on manual region of interest (ROI) placement. This study compared ALPS indices in treatment-naïve, de novo diagnosed patients with Parkinson's disease (PD), patients with isolated REM behavior disorder (iRBD), and healthy controls using both manual and automatic approaches to the ROI selection used in ALPS-index calculation. ALPS indices were analyzed bilaterally and correlated with clinical severity (MDS-UPDRS) and nigrostriatal denervation (DAT-SPECT). ANCOVA revealed significant inter-group differences using both manual (p = 0.018) and automatic (p = 0.002) ROI selection methods. The automatic ROI selection approach showed significantly lower ALPS indices in PD compared to controls (p = 0.001) and iRBD (p = 0.009). ALPS indices correlated with symptom severity and nigrostriatal denervation. These findings underscore the reliability of the automatic ROI placement approach for ALPS index calculation and may indicate early glymphatic alterations in Parkinson's disease.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: Patients with synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease (PD) frequently display speech and language abnormalities. We explore the diagnostic potential of automated linguistic analysis of natural spontaneous speech to differentiate MSA and PD. METHODS: Spontaneous speech of 39 participants with MSA compared to 39 drug-naive PD and 39 healthy controls matched for age and sex was transcribed and linguistically annotated using automatic speech recognition and natural language processing. A quantitative analysis was performed using 6 lexical and syntactic and 2 acoustic features. Results were compared with human-controlled analysis to assess the robustness of the approach. Diagnostic accuracy was evaluated using sensitivity analysis. RESULTS: Despite similar disease duration, linguistic abnormalities were generally more severe in MSA than in PD, leading to high diagnostic accuracy with an area under the curve of 0.81. Compared to controls, MSA showed decreased grammatical component usage, more repetitive phrases, shorter sentences, reduced sentence development, slower articulation rate, and increased duration of pauses, whereas PD had only shorter sentences, reduced sentence development, and longer pauses. Only slower articulation rate was distinctive for MSA while unchanged for PD relative to controls. The highest correlation was found between bulbar/pseudobulbar clinical score and sentence length (r = -0.49, p = 0.002). Despite the relatively high severity of dysarthria in MSA, a strong agreement between manually and automatically computed results was achieved. DISCUSSION: Automated linguistic analysis may offer an objective, cost-effective, and widely applicable biomarker to differentiate synucleinopathies with similar clinical manifestations.
- MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie * diagnóza patofyziologie komplikace MeSH
- Parkinsonova nemoc * diagnóza komplikace patofyziologie MeSH
- řeč fyziologie MeSH
- senioři MeSH
- zpracování přirozeného jazyka MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. METHODS: Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3 T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. RESULTS: VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. CONCLUSIONS: iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.
Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.
- MeSH
- lidé MeSH
- mozek diagnostické zobrazování patologie MeSH
- Parkinsonova nemoc * komplikace MeSH
- porucha chování v REM spánku * diagnostické zobrazování MeSH
- substantia nigra diagnostické zobrazování patologie MeSH
- synukleinopatie * komplikace patologie MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Striosomes and matrix are two compartments that comprise the striatum, each having its own distinct immunohistochemical properties, function, and connectivity. It is currently not clear whether prodromal or early manifest Parkinson's disease (PD) is associated with any striatal matrix or striosomal abnormality. Recently, a method of striatal parcellation using probabilistic tractography has been described and validated, using the distinct connectivity of these two compartments to identify voxels with striosome- and matrix-like connectivity. The goal of this study was to use this approach in tandem with DAT-SPECT, a method used to quantify the level of nigrostriatal denervation, to analyze the striatum in populations of de novo diagnosed, treatment-naïve patients with PD, isolated REM behavioral disorder (iRBD) patients, and healthy controls. We discovered a shift in striatal connectivity, which showed correlation with nigrostriatal denervation. Patients with PD exhibited a significantly higher matrix-like volume and associated connectivity than healthy controls and higher matrix-associated connectivity than iRBD patients. In contrast, the side with less pronounced nigrostriatal denervation in PD and iRBD patients showed a decrease in striosome-like volume and associated connectivity indices. These findings could point to a compensatory neuroplastic mechanism in the context of nigrostriatal denervation and open a new avenue in the investigation of the pathophysiology of Parkinson's disease.
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.
- MeSH
- demence s Lewyho tělísky * diagnostické zobrazování MeSH
- dopamin * metabolismus MeSH
- jednofotonová emisní výpočetní tomografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * diagnostické zobrazování komplikace MeSH
- porucha chování v REM spánku * diagnostické zobrazování MeSH
- presynaptická zakončení metabolismus MeSH
- senioři MeSH
- strojové učení * MeSH
- synukleinopatie * diagnostické zobrazování MeSH
- zobrazení dopaminergního systému MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
