Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.
- MeSH
- antiparkinsonika škodlivé účinky MeSH
- dysartrie etiologie komplikace MeSH
- kvalita života MeSH
- levodopa * škodlivé účinky MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování farmakoterapie MeSH
- poruchy řeči diagnostické zobrazování etiologie MeSH
- řeč fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.
- MeSH
- hluboká mozková stimulace * škodlivé účinky MeSH
- kognitivní dysfunkce * etiologie diagnostické zobrazování patofyziologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- neuropsychologické testy MeSH
- nucleus subthalamicus * diagnostické zobrazování MeSH
- Parkinsonova nemoc * terapie diagnostické zobrazování patologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- 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
In Parkinson's disease (PD), impaired gait and cognition affect daily activities, particularly in the more advanced stages of the disease. This study investigated the relationship between gait parameters, cognitive performance, and brain morphology in patients with early untreated PD. 64 drug-naive PD patients and 47 healthy controls (HC) participated in the study. Single- and dual-task gait (counting task) were examined using an expanded Timed Up & Go Test measured on a GaitRite walkway. Measurements included gait speed, stride length, and cadence. A brain morphometry analysis was performed on T1-weighted magnetic resonance (MR) images. In PD patients compared to HC, gait analysis revealed reduced speed (p < 0.001) and stride length (p < 0.001) in single-task gait, as well as greater dual-task cost (DTC) for speed (p = 0.007), stride length (p = 0.014) and cadence (p = 0.029). Based on the DTC measures in HC, PD patients were further divided into two subgroups with normal DTC (PD-nDTC) and abnormally increased DTC (PD-iDTC). For PD-nDTC, voxel-based morphometric correlation analysis revealed a positive correlation between a cluster in the left primary motor cortex and stride-length DTC (r = 0.57, p = 0.027). For PD-iDTC, a negative correlation was found between a cluster in the right lingual gyrus and the DTC for gait cadence (r=-0.35, pFWE = 0.018). No significant correlations were found in HC. The associations found between brain morphometry and gait performance with a concurrent cognitive task may represent the substrate for gait and cognitive impairment occurring since the early stages of PD.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozek * diagnostické zobrazování patologie patofyziologie MeSH
- neurologické poruchy chůze * etiologie patofyziologie diagnostické zobrazování patologie MeSH
- neuropsychologické testy MeSH
- Parkinsonova nemoc * diagnostické zobrazování patofyziologie patologie komplikace MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Parkinson's disease (PD) is a common neurodegenerative disease, and apart from a few rare genetic causes, its pathogenesis remains largely unclear. Recent scientific interest has been captured by the involvement of iron biochemistry and the disruption of iron homeostasis, particularly within the brain regions specifically affected in PD. The advent of Quantitative Susceptibility Mapping (QSM) has enabled non-invasive quantification of brain iron in vivo by MRI, which has contributed to the understanding of iron-associated pathogenesis and has the potential for the development of iron-based biomarkers in PD. This review elucidates the biochemical underpinnings of brain iron accumulation, details advancements in iron-sensitive MRI technologies, and discusses the role of QSM as a biomarker of iron deposition in PD. Despite considerable progress, several challenges impede its clinical application after a decade of QSM studies. The initiation of multi-site research is warranted for developing robust, interpretable, and disease-specific biomarkers for monitoring PD disease progression.
- MeSH
- biologické markery MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mapování mozku metody MeSH
- neurodegenerativní nemoci * MeSH
- neurozobrazování MeSH
- Parkinsonova nemoc * diagnostické zobrazování patologie MeSH
- progrese nemoci MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Assessing imaging biomarker in the prodromal and early phases of Parkinson's disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance. Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system. Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD.
- MeSH
- biologické markery * metabolismus analýza MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- neurozobrazování metody MeSH
- optická koherentní tomografie metody MeSH
- Parkinsonova nemoc * diagnostické zobrazování metabolismus diagnóza MeSH
- pozitronová emisní tomografie MeSH
- prodromální symptomy * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Transkraniální sonografie je jednou z modalit transkraniálního sonografického vyšetření, které umožňuje zobrazení nitrolebních struktur v ultrazvukovém B‐obraze. Pomocí tohoto vyšetření je možno hodnotit změny echogenity, popř. rozměrů vybraných mozkových struktur, např. substantia nigra, ncl. raphe, ncl. lentiformis, ncl. caudatus, inzuly, mediotemporálního laloku či komorového systému. Díky tomu lze transkraniální sonografii využít jako pomocné vyšetření v diagnostice a diferenciální diagnostice neurodegenerativních a dalších neurologických a psychiatrických onemocnění centrální nervové soustavy. Typickým nálezem u Parkinsonovy nemoci je hyperechogenní substantia nigra s asymetrickým stranovým nálezem. Jelikož lze tento znak detekovat i mnoho desetiletí před samotným rozvojem motorických příznaků Parkinsonovy nemoci, lze toto vyšetření využít i při stanovení rizika rozvoje nemoci, a to především v kombinaci s dalšími testy.
Transcranial sonography is one of the modalities of transcranial sonographic examination, which enables to visualize intracranial structures in ultrasound B Mode. Using this examination, it is possible to evaluate changes in echogenicity or dimensions of selected brain structures, e.g. substantia nigra, ncl. raphe, ncl. lentiformis, ncl. caudate, insula, mediotemporal lobe or ventricular system. Thanks to this, transcranial sonography can be used as an auxiliary examination in the diagnosis and differential diagnosis of neurodegenerative and other neurological and psychiatric diseases of the central nervous system. A typical finding in Parkinson's disease is a asymmetric hyperechogenic substantia nigra. Since this sign can be detected many decades before the development of motor symptoms of Parkinson's disease itself, this examination can also be used to determine the risk of developing the disease, especially in combination with other tests.
In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.
INTRODUCTION: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI). METHODS: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001. RESULTS: PD patients differed from HC in attention domain z-scores (p < 0.0001). In terms of tablet parameters, the groups differed in Shannon entropy (horizontal in-air, p = 0.003), which quantifies the movements between two strokes. In PD, a correlation was found between the median of Shannon entropy (horizontal in-air) and attention z-scores (R = -0.55, p = 0.006). The VBM revealed an association between our drawing parameter of interest and gray matter (GM) volume variability in the right superior parietal lobe (SPL). CONCLUSION: Using a digitizing tablet during the PCT, we identified a novel entropy-based parameter that differed between the nondemented PD and HC groups. This in-air parameter correlated with the level of attention and was linked to GM volume variability of the region engaged in spatial attention.
- MeSH
- entropie MeSH
- kognitivní dysfunkce * MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- neuropsychologické testy MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování psychologie MeSH
- šedá hmota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The mechanisms underlying speech abnormalities in Parkinson's disease (PD) remain poorly understood, with most of the available evidence based on male patients. This study aimed to estimate the occurrence and characteristics of speech disorder in early, drug-naive PD patients with relation to gender and dopamine transporter imaging. METHODS: Speech samples from 60 male and 40 female de novo PD patients as well as 60 male and 40 female age-matched healthy controls were analyzed. Quantitative acoustic vocal assessment of 10 distinct speech dimensions related to phonation, articulation, prosody, and speech timing was performed. All patients were evaluated using [123]I-2b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single-photon emission computed tomography and Montreal Cognitive Assessment. RESULTS: The prevalence of speech abnormalities in the de novo PD cohort was 56% for male and 65% for female patients, mainly manifested with monopitch, monoloudness, and articulatory decay. Automated speech analysis enabled discrimination between PD and controls with an area under the curve of 0.86 in men and 0.93 in women. No gender-specific speech dysfunction in de novo PD was found. Regardless of disease status, females generally showed better performance in voice quality, consonant articulation, and pauses production than males, who were better only in loudness variability. The extent of monopitch was correlated to nigro-putaminal dopaminergic loss in men (r = 0.39, p = 0.003) and the severity of imprecise consonants was related to cognitive deficits in women (r = -0.44, p = 0.005). CONCLUSIONS: Speech abnormalities represent a frequent and early marker of motor abnormalities in PD. Despite some gender differences, our findings demonstrate that speech difficulties are associated with nigro-putaminal dopaminergic deficits.
- MeSH
- dopamin MeSH
- jednofotonová emisní výpočetní tomografie MeSH
- lidé MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování MeSH
- poruchy řeči diagnostické zobrazování etiologie MeSH
- řeč * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
