INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.
- MeSH
- Alzheimerova nemoc * patologie MeSH
- atrofie patologie MeSH
- demence s Lewyho tělísky * diagnostické zobrazování patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozková kůra patologie MeSH
- pohlavní dimorfismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíle: V roce 2022 byl připraven adaptovaný Klinický doporučený postup (KDP) zahrnující diagnos- ticko-terapeutické postupy u pacientů s Parkinsonovou nemocí. Doporučení mají pomoci odborníkům z klinické praxe v rozhodovacích schopnostech a cílem KDP je zkvalitnění poskytovaných služeb na národní úrovni a zefektivnění nákladovosti. Metodika: Retrospektivní dotazníkový průzkum s cílem ověřit využití KDP odborníky z klinické praxe (lékaři a nelékařští zdravotničtí pracovníci). Sběr dat byl realizován od začátku června do konce července v roce 2023 sdílením na webovém portále České neurologické společnosti (ČNS) a Extrapyramidovou sekcí ČNS v elektronické podobě. Využit byl dotazník vlastní konstrukce a data byla analyzována pomocí deskriptivní analýzy. Výsledky: Průzkumu se zúčastnilo celkem 51 respondentů (30 žen a 21 mužů) průměrného věku 43,3 roku. V souboru bylo zastoupeno 31 lékařů, tj. 61 % (12 ambulantní péče a 19 lůžková péče), a 20 sester, tj. 39 % (11 ambulantní péče a 9 lůžková péče), s průměrnou délkou klinické praxe 15,2 roku. Využívání KDP v plném znění neuvedla ani jedna všeobecná sestra ve srovnání s lékaři, kde jich šest uvedlo využívání KDP (p = 0,036) a ohodnotilo jej ve vysoké kvalitě. V souvislosti s dalšími návrhy na aktualizaci KDP bylo doporučeno doplnění nových léčivých přípravků (n = 5) a komplexní rozpracování informací pro pacienty (n = 2). Závěr: Parkinsonova nemoc představuje významnou ekonomickou zátěž pro zdravotnické systémy a snížení kvality života pro pacienty v rámci postupné progrese onemocnění. KDP na národní úrovni má za cíl snižovat geografické, demografické a další rozdíly v přístupu k pacientům. Bude realizována pravidelná aktualizace KDP diagnostiky a léčby Parkinsonovy nemoci dle potřeb Extrapyramidové sekce. Doplněna budou doporučení s posledními registrovanými léčivy a diagnosticko- -terapeutickými postupy a také budou v rámci aktualizace připravena komplexní doporučení pro pacienty v laickém jazyce.
Aims: Adapted Clinical Practice Guidelines (CPG) covering diagnostic and therapeutic procedures for patients with Parkinson‘s disease were developed in 2022. The recommendations are intended to assist clinical practitioners in their decision-making abilities, and the CPG aims to improve the quality of services provided nationally including cost-effectiveness. Methodology: A retrospective questionnaire survey to examine the use of CPG by clinical practitioners (physicians and non-physician health professionals). Data collection was conducted from early June to late July in 2023 by sharing it electronically on the Czech Neurological Society (CNS) web portal and the Extrapyramidal Section of the CNS. A self-constructed questionnaire was used and data were analyzed using descriptive analysis. Results: A total of 51 respondents (30 women and 21 men) took part in the survey with an average age of 43.3 years. There were 31 physicians, i.e. 61% (12 ambulatory care and 19 inpatient care) and 20 nurses, i.e. 39% (11 ambulatory care and 9 inpatient care) with an average length of clinical experience of 15.2 years. None of the general nurses reported full use of CPG compared to physicians, where 6 of them reported using CPG (P = 0.036) and rated it as high quality. Other suggestions for updating the CPG included the addition of new medicines (N = 5) and comprehensive development of patient information (N = 2). Conclusion: Parkinson‘s disease represents a significant economic burden on healthcare systems and a reduction in quality of life for patients as the disease progresses. The national CPG aims to reduce geographic, demographic, and other disparities in patient access. Regular updates to the CPG on the diagnosis and treatment of Parkinson‘s disease will be implemented as required by the Extrapyramidal Section. Recommendations will be updated with the latest registered drugs and diagnostic and therapeutic procedures, and comprehensive recommendations for patients in lay language will be prepared as part of the update.
AIM OF STUDY: To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY: Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS: A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS: Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.
- MeSH
- antiparkinsonika * škodlivé účinky aplikace a dávkování MeSH
- fixní kombinace léků * MeSH
- gely * MeSH
- karbidopa * aplikace a dávkování škodlivé účinky MeSH
- levodopa * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- polyneuropatie * chemicky indukované farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři 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
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: The known impairments of the cardiovascular system in Parkinson ́s disease (PD) are caused by autonomic dysfunction and manifested mainly in postural hypotension, chronotropic insufficiency, and reduced heart rate variability. Other dysfunctions, mainly stress response, arrhythmia occurrence, and heart morphology changes, are still the subject of research. OBJECTIVES: To assess the heart rate and blood pressure reaction during exercise, advanced measurements of heart volumes and mass using cardiac magnetic resonance (CMR), and occurrence of arrhythmias in PD patients. METHODS: Thirty PD patients (19 men, mean age 57.5 years) without known cardiac comorbidities underwent bicycle ergometry, electrocardiogram Holter monitoring and CMR. Exercise and CMR parameters were compared with controls (24 subjects for ergometry, 20 for CMR). RESULTS: PD patients had lower baseline systolic blood pressure (SBP) (117.8 vs. 128.3 mmHg, p < 0.01), peak SBP (155.8 vs. 170.8 mmHg, p < 0.05), and lower heart rate increase (49.7 vs. 64.3 beats per minute, p < 0.01). PD patients had higher indexed left and right ventricular end-diastolic volumes (68.5 vs. 57.3, p = 0.003 and 73.5 vs. 61.0 mL/m2 , respectively) and also indexed left and right ventricular end-systolic volumes (44.1 vs. 39.0, p = 0.013 and 29.0 vs. 22.0 mL/m2 , p = 0.013, respectively). A high prevalence of atrial fibrillation (8 subjects, 26.7%) was found. CONCLUSIONS: This novel study combining functional and structural approaches showed that PD is linked with weaker blood pressure and heart rate reaction during exercise, increased myocardial mass and heart volumes compared to controls, and a high prevalence of atrial fibrillation.
- MeSH
- elektrokardiografie MeSH
- fibrilace síní * komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- Parkinsonova nemoc * komplikace epidemiologie MeSH
- srdce MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: Endoplasmic reticulum stress followed by the unfolded protein response is one of the cellular mechanisms contributing to the progression of α-synuclein pathology in Parkinson's disease and other Lewy body diseases. We aimed to investigate the activation of endoplasmic reticulum stress and its correlation with α-synuclein pathology in human post-mortem brain tissue. METHODS: We analysed brain tissue from 45 subjects-14 symptomatic patients with Lewy body disease, 19 subjects with incidental Lewy body disease, and 12 healthy controls. The analysed brain regions included the medulla, pons, midbrain, striatum, amygdala and entorhinal, temporal, frontal and occipital cortex. We analysed activation of endoplasmic reticulum stress via levels of the unfolded protein response-related proteins (Grp78, eIF2α) and endoplasmic reticulum stress-regulating neurotrophic factors (MANF, CDNF). RESULTS: We showed that regional levels of two endoplasmic reticulum-localised neurotrophic factors, MANF and CDNF, did not change in response to accumulating α-synuclein pathology. The concentration of MANF negatively correlated with age in specific regions. eIF2α was upregulated in the striatum of Lewy body disease patients and correlated with increased α-synuclein levels. We found the upregulation of chaperone Grp78 in the amygdala and nigral dopaminergic neurons of Lewy body disease patients. Grp78 levels in the amygdala strongly correlated with soluble α-synuclein levels. CONCLUSIONS: Our data suggest a strong but regionally specific change in Grp78 and eIF2α levels, which positively correlates with soluble α-synuclein levels. Additionally, MANF levels decreased in dopaminergic neurons in the substantia nigra. Our research suggests that endoplasmic reticulum stress activation is not associated with Lewy pathology but rather with soluble α-synuclein concentration and disease progression.
- MeSH
- alfa-synuklein * metabolismus MeSH
- biologické markery metabolismus MeSH
- chaperon endoplazmatického retikula BiP * metabolismus MeSH
- demence s Lewyho tělísky * patologie metabolismus MeSH
- eukaryotický iniciační faktor 2 * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek metabolismus patologie MeSH
- neurotrofní faktory metabolismus MeSH
- proteiny tepelného šoku * metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- signální dráha UPR * fyziologie MeSH
- stres endoplazmatického retikula fyziologie MeSH
- upregulace * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Alzheimerova nemoc farmakoterapie patofyziologie MeSH
- bipolární porucha farmakoterapie patofyziologie MeSH
- centrální nervový systém * fyziologie MeSH
- deprese farmakoterapie patofyziologie MeSH
- klinická studie jako téma MeSH
- kyselina arachidonová fyziologie MeSH
- kyseliny dokosahexaenové farmakologie fyziologie terapeutické užití MeSH
- lidé MeSH
- mozek embryologie růst a vývoj MeSH
- nenasycené mastné kyseliny * farmakologie fyziologie terapeutické užití MeSH
- neurodegenerativní nemoci farmakoterapie klasifikace patofyziologie MeSH
- novorozenec MeSH
- Parkinsonova nemoc farmakoterapie patofyziologie MeSH
- schizofrenie farmakoterapie patofyziologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.
- MeSH
- hluboká mozková stimulace * metody MeSH
- kognice fyziologie MeSH
- kognitivní dysfunkce * etiologie terapie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- nucleus subthalamicus * MeSH
- Parkinsonova nemoc * terapie patofyziologie MeSH
- retrospektivní studie MeSH
- senioři 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
Advancements in deep learning speech representations have facilitated the effective use of extensive unlabeled speech datasets for Parkinson's disease (PD) modeling with minimal annotated data. This study employs the non-fine-tuned wav2vec 1.0 architecture to develop machine learning models for PD speech diagnosis tasks, such as cross-database classification and regression to predict demographic and articulation characteristics. The primary aim is to analyze overlapping components within the embeddings on both classification and regression tasks, investigating whether latent speech representations in PD are shared across models, particularly for related tasks. Firstly, evaluation using three multi-language PD datasets showed that wav2vec accurately detected PD based on speech, outperforming feature extraction using mel-frequency cepstral coefficients in the proposed cross-database classification scenarios. In cross-database scenarios using Italian and English-read texts, wav2vec demonstrated performance comparable to intra-dataset evaluations. We also compared our cross-database findings against those of other related studies. Secondly, wav2vec proved effective in regression, modeling various quantitative speech characteristics related to articulation and aging. Ultimately, subsequent analysis of important features examined the presence of significant overlaps between classification and regression models. The feature importance experiments discovered shared features across trained models, with increased sharing for related tasks, further suggesting that wav2vec contributes to improved generalizability. The study proposes wav2vec embeddings as a next promising step toward a speech-based universal model to assist in the evaluation of PD.
- MeSH
- databáze faktografické * MeSH
- deep learning MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * patofyziologie MeSH
- řeč * fyziologie MeSH
- senioři MeSH
- strojové učení MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
