BACKGROUND: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer's disease (AD) and patients with AD in comorbidity with synucleinopathies. METHODS: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer's disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. RESULTS: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. CONCLUSION: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

• Klíčová slova
• Alzheimer`s disease, archicortex, bulbous neuritic changes, neocortex, neuritic plaques, synucleinopathy,
• MeSH
• Alzheimerova nemoc patologie   MeSH
• amyloidní plaky patologie   MeSH
• hipokampus patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• neurity patologie   MeSH
• pilotní projekty MeSH
• senioři MeSH
• synukleinopatie patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

• MeSH
• alfa-synuklein MeSH
• biologické markery * MeSH
• lidé MeSH
• porucha chování v REM spánku komplikace   diagnóza   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• synukleinopatie diagnóza   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• alfa-synuklein MeSH
• biologické markery * 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
• presynaptické terminály 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

• MeSH
• lidé MeSH
• porucha chování v REM spánku * etiologie   MeSH
• primární dysautonomie * MeSH
• synukleinopatie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH

Neuromelanin (NM) is a black pigment located in the brain in substantia nigra pars compacta (SN) and locus coeruleus. Its loss is directly connected to the loss of nerve cells in this part of the brain, which plays a role in Parkinson's Disease. Magnetic resonance imaging (MRI) is an ideal tool to monitor the amount of NM in the brain in vivo. The aim of the study was the development of tools and methodology for the quantification of NM in a special neuromelanin-sensitive MRI images. The first approach was done by creating regions of interest, corresponding to the anatomical position of SN based on an anatomical atlas and determining signal intensity threshold. By linking the anatomical and signal intensity information, we were able to segment the SN. As a second approach, the neural network U-Net was used for the segmentation of SN. Subsequently, the volume characterizing the amount of NM in the SN region was calculated. To verify the method and the assumptions, data available from various patient groups were correlated. The main benefit of this approach is the observer-independency of quantification and facilitation of the image processing process and subsequent quantification compared to the manual approach. It is ideal for automatic processing many image sets in one batch.

• MeSH
• deep learning * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• melaniny analýza   MeSH
• počítačové zpracování obrazu MeSH
• prodromální symptomy MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• substantia nigra diagnostické zobrazování   MeSH
• synukleinopatie diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• melaniny MeSH
• neuromelanin MeSH Prohlížeč

BACKGROUND: Impairments of olfactory and speech function are likely early prodromal symptoms of α-synucleinopathy. OBJECTIVE: The aim of this study is to assess whether dysprosody is present in isolated rapid eye movement sleep behavior disorder (iRBD) with hyposmia/anosmia and a normal nigrostriatal system. METHODS: Pitch variability during speech was investigated in 17 iRBD subjects with normal olfactory function (iRBD-NOF), 30 iRBD subjects with abnormal olfactory function (iRBD-AOF), and 50 healthy controls. iRBD subjects were evaluated using the University of Pennsylvania Smell Identification Test and [123I]-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT). All iRBD subjects completed the 24-month follow-up with DAT-SPECT, speech, and olfactory testing. RESULTS: At baseline, only iRBD-AOF showed monopitch when compared to iRBD-NOF (P = 0.04) and controls (P = 0.03), with no difference between iRBD-NOF and controls (P = 1). At follow-up, dysprosody progressed only in iRBD-AOF with abnormal DAT-SPECT (P = 0.03). CONCLUSION: Prosody is impaired in hyposmic but not in normosmic iRBD subjects before the nigrostriatal dopaminergic transmission is affected (Braak stage 2). © 2021 International Parkinson and Movement Disorder Society.

• Klíčová slova
• dopamine transporter imaging, dysarthria, olfactory, prodromal synucleinopathy biomarker, speech disorder,
• MeSH
• dopamin metabolismus   MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• lidé MeSH
• porucha chování v REM spánku * MeSH
• poruchy čichu * diagnostické zobrazování   etiologie   MeSH
• synukleinopatie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dopamin MeSH

BACKGROUND: Patients with synucleinopathies frequently display language abnormalities. However, whether patients with isolated rapid eye movement sleep behavior disorder (iRBD) have prodromal language impairment remains unknown. OBJECTIVE: We examined whether the linguistic abnormalities in iRBD can serve as potential biomarkers for conversion to synucleinopathy, including the possible effect of mild cognitive impairment (MCI), speaking task, and automation of analysis procedure. METHODS: We enrolled 139 Czech native participants, including 40 iRBD without MCI and 14 iRBD with MCI, compared with 40 PD without MCI, 15 PD with MCI, and 30 healthy control subjects. Spontaneous discourse and story-tale narrative were transcribed and linguistically annotated. A quantitative analysis was performed computing three linguistic features. Human annotations were compared with fully automated annotations. RESULTS: Compared with control subjects, patients with iRBD showed poorer content density, reflecting the reduction of content words and modifiers. Both PD and iRBD subgroups with MCI manifested less occurrence of unique words and a higher number of n-grams repetitions, indicating poorer lexical richness. The spontaneous discourse task demonstrated language impairment in iRBD without MCI with an area under the curve of 0.72, while the story-tale narrative task better reflected the presence of MCI, discriminating both PD and iRBD subgroups with MCI from control subjects with an area under the curve of up to 0.81. A strong correlation between manually and automatically computed results was achieved. CONCLUSIONS: Linguistic features might provide a reliable automated method for detecting cognitive decline caused by prodromal neurodegeneration in subjects with iRBD, providing critical outcomes for future therapeutic trials. © 2022 International Parkinson and Movement Disorder Society.

• Klíčová slova
• Parkinson's disease, discourse, lexical features, prodromal synucleinopathy biomarker, spoken language,
• MeSH
• kognitivní dysfunkce * diagnóza   MeSH
• lidé MeSH
• lingvistika MeSH
• Parkinsonova nemoc * komplikace   MeSH
• porucha chování v REM spánku * diagnóza   MeSH
• synukleinopatie * MeSH
• vývojové poruchy řeči * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. METHODS: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis. RESULTS: A 5'-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5' risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3' of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3' variant rs356182) had an opposite direction of effect in iRBD compared to PD. INTERPRETATION: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3' of SNCA. Several 5' SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies. ANN NEUROL 2020;87:584-598.

• MeSH
• alfa-synuklein genetika   MeSH
• demence s Lewyho tělísky genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• odds ratio MeSH
• Parkinsonova nemoc genetika   MeSH
• porucha chování v REM spánku genetika   MeSH
• prodromální symptomy * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• synukleinopatie genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa-synuklein MeSH
• SNCA protein, human MeSH Prohlížeč

INTRODUCTION: Early identification of Parkinson's disease (PD) in its prodromal stage has fundamental implications for the future development of neuroprotective therapies. However, no sufficiently accurate biomarkers of prodromal PD are currently available to facilitate early identification. The vocal assessment of patients with isolated rapid eye movement sleep behaviour disorder (iRBD) and PD appears to have intriguing potential as a diagnostic and progressive biomarker of PD and related synucleinopathies. METHODS AND ANALYSIS: Speech patterns in the spontaneous speech of iRBD, early PD and control participants' voice calls will be collected from data acquired via a developed smartphone application over a period of 2 years. A significant increase in several aspects of PD-related speech disorders is expected, and is anticipated to reflect the underlying neurodegeneration processes. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the General University Hospital in Prague, Czech Republic and all the participants will provide written, informed consent prior to their inclusion in the research. The application satisfies the General Data Protection Regulation law requirements of the European Union. The study findings will be published in peer-reviewed journals and presented at international scientific conferences.

• Klíčová slova
• Audiology, Parkinson-s disease, Speech pathology,
• MeSH
• biologické markery MeSH
• chytrý telefon MeSH
• lidé MeSH
• Parkinsonova nemoc * komplikace   diagnóza   MeSH
• řeč MeSH
• synukleinopatie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

OBJECTIVES: Hyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity. PATIENTS/METHODS: A total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects. RESULTS AND CONCLUSION: The abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm2) was higher compared to iRBD (0.07 ± 0.07 cm2; p < 0.0001) and controls (0.05 ± 0.03 cm2; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15). Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = -0.13, p = 0.29), nor in PD (r = -0.19, p = 0.22). The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.

• Klíčová slova
• Dopamine transporter imaging, Idiopathic rapid-eye-movement sleep behavior disorder, Neuroimaging, Parkinson's disease, Substantia nigra hyperechogenicity, Transcranial sonography,
• MeSH
• jednofotonová emisní výpočetní tomografie MeSH
• lidé MeSH
• nortropany MeSH
• porucha chování v REM spánku * diagnostické zobrazování   patofyziologie   MeSH
• radioizotopy jodu MeSH
• substantia nigra * diagnostické zobrazování   patofyziologie   MeSH
• synukleinopatie * diagnostické zobrazování   patofyziologie   MeSH
• ultrasonografie dopplerovská transkraniální MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Iodine-123 MeSH Prohlížeč
• ioflupane MeSH Prohlížeč
• nortropany MeSH
• radioizotopy jodu MeSH