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.

• Klíčová slova
• MRI, PET, Parkinson’s disease, biomarker, diagnosis, neuroimaging, prodromal, progression,
• 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
• Názvy látek
• biologické markery * MeSH

AIM: To investigate the presence and relationship of temporal speech and gait parameters in patients with postural instability/gait disorder (PIGD) and tremor-dominant (TD) motor subtypes of Parkinson's disease (PD). METHODS: Speech samples and instrumented walkway system assessments were acquired from a total of 60 de-novo PD patients (40 in TD and 20 in PIGD subtype) and 40 matched healthy controls. Objective acoustic vocal assessment of seven distinct speech timing dimensions was related to instrumental gait measures including velocity, cadence, and stride length. RESULTS: Compared to controls, PIGD subtype showed greater consonant timing abnormalities by prolonged voice onset time (VOT) while also shorter stride length during both normal walking and dual task, while decreased velocity and cadence only during dual task. Speaking rate was faster in PIGD than TD subtype. In PIGD subtype, prolonged VOT correlated with slower gait velocity (r = -0.56, p = 0.01) and shorter stride length (r = -0.59, p = 0.008) during normal walking, whereas relationships were also found between decreased cadence in dual task and irregular alternating motion rates (r = -0.48, p = 0.04) and prolonged pauses (r = -0.50, p = 0.03). No correlation between speech and gait was detected in TD subtype. CONCLUSION: Our findings suggest that speech and gait rhythm disorder share similar underlying pathomechanisms specific for PIGD subtype.

• Klíčová slova
• Parkinson's disease, dysarthria, gait, postural instability gait difficulty, speech disorder,
• MeSH
• chůze (způsob) MeSH
• chůze MeSH
• lidé MeSH
• neurologické poruchy chůze * etiologie   MeSH
• Parkinsonova nemoc * komplikace   MeSH
• posturální rovnováha MeSH
• řeč MeSH
• tremor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Oxidative stress supposedly plays a role in the pathogenesis of Parkinson's disease (PD). Uric acid (UA), a powerful antioxidant, is lowered in PD while allantoin, the oxidation product of UA and known biomarker of oxidative stress, was not systematically studied in PD. We aim to compare serum and cerebrospinal fluid (CSF) levels of UA, allantoin, and allantoin/UA ratio in de novo PD patients and controls, and evaluate their associations with clinical severity and the degree of substantia nigra degeneration in PD. We measured serum and CSF levels of UA, allantoin, and allantoin/UA ratio in 86 PD patients (33 females, mean age 57.9 (SD 12.6) years; CSF levels were assessed in 51 patients) and in 40 controls (19 females, 56.7 (14.1) years). PD patients were examined using Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson Disease-Autonomic (SCOPA-AUT), the University of Pennsylvania Smell Identification Test (UPSIT), one-night video-polysomnography, and dopamine transporter single-photon emission computed tomography (DAT-SPECT). Serum allantoin and allantoin/UA ratio were significantly increased in the PD group compared to controls (p < 0.001 and p = 0.002, respectively). Allantoin/UA ratios in serum and CSF were positively associated with the SCOPA-AUT score (p = 0.005 and 0.031, respectively) and RBD presence (p = 0.044 and 0.028, respectively). In conclusion, serum allantoin and allantoin/UA ratio are elevated in patients with de novo PD. Allantoin/UA ratio in serum and CSF is associated with autonomic dysfunction and RBD presence, indicating that higher systemic oxidative stress occurs in PD patients with more diffuse neurodegenerative changes.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: This multilanguage study used simple speech recording and high-end pattern analysis to provide sensitive and reliable noninvasive biomarkers of prodromal versus manifest α-synucleinopathy in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and early-stage Parkinson disease (PD). METHODS: We performed a multicenter study across the Czech, English, German, French, and Italian languages at 7 centers in Europe and North America. A total of 448 participants (337 males), including 150 with iRBD (mean duration of iRBD across language groups 0.5-3.4 years), 149 with PD (mean duration of disease across language groups 1.7-2.5 years), and 149 healthy controls were recorded; 350 of the participants completed the 12-month follow-up. We developed a fully automated acoustic quantitative assessment approach for the 7 distinctive patterns of hypokinetic dysarthria. RESULTS: No differences in language that impacted clinical parkinsonian phenotypes were found. Compared with the controls, we found significant abnormalities of an overall acoustic speech severity measure via composite dysarthria index for both iRBD (p = 0.002) and PD (p < 0.001). However, only PD (p < 0.001) was perceptually distinct in a blinded subjective analysis. We found significant group differences between PD and controls for monopitch (p < 0.001), prolonged pauses (p < 0.001), and imprecise consonants (p = 0.03); only monopitch was able to differentiate iRBD patients from controls (p = 0.004). At the 12-month follow-up, a slight progression of overall acoustic speech impairment was noted for the iRBD (p = 0.04) and PD (p = 0.03) groups. INTERPRETATION: Automated speech analysis might provide a useful additional biomarker of parkinsonism for the assessment of disease progression and therapeutic interventions. ANN NEUROL 2021;90:62-75.

• MeSH
• biologické markery MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc diagnóza   patofyziologie   MeSH
• porucha chování v REM spánku diagnóza   patofyziologie   MeSH
• prodromální symptomy MeSH
• progrese nemoci MeSH
• řeč fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři 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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• biologické markery MeSH

Hypokinetic dysarthria is a multidimensional impairment affecting all main speech subsystems with variable patterns and severity across individual Parkinson's disease (PD) patients. We can thus assume that inter-individual abnormal speech patterns are related to the various clinical subtypes of PD with different prominent motor symptoms. The aim of this cross-sectional study was to compare speech disorder between patients with the postural instability/gait difficulty (PIGD) and tremor-dominant (TD) motor phenotypes of PD. Speech samples were acquired from a total of 63 participants, including 21 PIGD patients, 21 TD patients, and 21 healthy controls. Quantitative acoustic vocal assessment of 12 unique speech dimensions related to phonation, vocal tremor, oral diadochokinesis, articulation, prosody and speech timing was performed. Speech impairment was more pronounced in the PIGD group than in the TD group, with an area under the curve of 0.76. Patients in the PIGD group manifested abnormalities in pitch breaks, articulatory decay, decreased rate of follow-up speech segments and inappropriate silences, apart from monopitch and irregular AMR that were affected in TD group as well. An abnormal vocal tremor was present in only 10% of PD patients, with no differences between the PD phenotypes. We found a correlation between non-motor symptom severity and speech timing (r = - 0.40, p = 0.009). The present study demonstrates that speech disorder reflects the underlying motor phenotypes. Vocal tremor appeared to be an isolated phenomenon that does not share similar pathophysiology with limb tremor.

• Klíčová slova
• Acoustic analyses, Dysarthria, Gait, Parkinson’s disease, Phenotype, Speech disorder, Vocal tremor,
• MeSH
• chůze (způsob) MeSH
• lidé MeSH
• neurologické poruchy chůze * MeSH
• Parkinsonova nemoc * komplikace   MeSH
• poruchy hlasu * etiologie   MeSH
• posturální rovnováha MeSH
• průřezové studie MeSH
• řeč MeSH
• tremor komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE OF REVIEW: We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. RECENT FINDINGS: The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion.

• Klíčová slova
• Alzheimer’s disease, Cognition, Gray matter atrophy, Parkinson’s disease, Structural magnetic resonance imaging,
• MeSH
• Alzheimerova nemoc patologie   psychologie   MeSH
• biologické markery MeSH
• kognice * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• Parkinsonova nemoc patologie   psychologie   MeSH
• šedá hmota patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• polysomnografie MeSH
• porucha chování v REM spánku metabolismus   patofyziologie   MeSH
• proteiny přenášející dopamin přes plazmatickou membránu metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• testy pro posouzení mentálních funkcí a demence MeSH
• vazba proteinů MeSH
• Check Tag
• 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
• proteiny přenášející dopamin přes plazmatickou membránu MeSH