AIM OF THE STUDY:This study aimed to analyze the most established genetic causes of Parkinson's disease (PD) in a cohort of patients from Czechia. CLINICAL RATIONALE FOR THE STUDY:PD is the second most common neurodegenerative disorder, with both genetic and environmental factors contributing to its pathogenesis. MATERIAL AND METHODS:We examined 214 patients with PD and 186 controls. Each patient underwent an examination using the Montreal Cognitive Assessment to assess the severity of cognitive impairment. Genetic analysis was performed using next- -generation sequencing and multiplex ligation-dependent probe amplification, focusing on mutations in GBA1, LRRK2, PINK1, PRKN, and SNCA genes. RESULTS:Clinically relevant mutations in GBA1 (pathogenic/likely pathogenic or severe/mild/risk variants) were the most frequently observed variants (n = 30; 14.0% of the PD cohort in total), including both known pathogenic mutations and the mild risk allele p.Glu365Lys (n = 12; 5.6% of cases), which was associated with earlier disease onset. Pathogenic mutations were also detected in LRRK2 (n = 2; 0.9%), SNCA (n = 1; 0.5%), and compound heterozygous mutations in PRKN (n = 2; 0.9%). Carriers of heterozygous mutations in PRKN were equally represented in patients and controls. No pathogenic PINK1 mutations were identified. Cognitive impairment was not significantly more frequent in GBA1 mutation carriers (p = 0.320). A positive family history of PD was more common in patients than in healthy controls (n = 51; 24% vs. n = 6; 3%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS:Our findings highlight notable genetic variability in Czech PD patients, particularly involving GBA1 mutations. However, these variants were not associated with early cognitive decline. The study underscores the value of genetic screening in PD and the need for further research into genotype-phenotype correlations.

This is a meta-analysis of studies that compare cognitive functioning between schizophrenia spectrum disorders and substance-induced psychotic disorder. PubMed, Web of Science and Google Scholar databases were systematically searched. Studies meeting the inclusion criteria were analysed. The risk of bias was assessed by QUADAS-2. Studies were pooled using a random effect model, and reported means and standard deviation (SD) were converted to Hedges’g which corrects for positive bias in Cohen’s d. Eighteen studies with 1092 patients were included in the analysis. The random effects overall meta-analysis model resulted in no overall effect. The meta-analysis for each cognitive domain showed a subtle but significant difference in executive functions, favouring substance-induced psychotic disorder. The equivalence of the groups was demonstrated by comparable performance in memory, attention, psychomotor speed, and intellectual functioning. This meta-analysis revealed that the cognitive impairment in patients with schizophrenia and substance-induced psychotic disorders groups may be quite similar. This finding indicates that the harmful effect of substance use, which leads to psychosis, may cause as severe impairment of cognitive functions as schizophrenia. Our findings also suggest that differences in executive functioning may differentiate schizophrenia from substance-induced psychotic disorder.

Over the course of Parkinson’s disease (PD), there is considerable intersubject variability in gray matter (GM) loss across a wide range of subcortical structures and cortical areas, which is often predictive of the clinical trajectory of the disease. The biological or clinical factors underlying these individual differences are not well understood. Obstructive sleep apnea (OSA) is a sleep-disordered breathing that is associated with an increased risk of cognitive impairment and neurodegeneration. In this study, we investigated whether moderate-to-severe OSA in untreated de novo PD is linked to more severe GM atrophy compared to PD without OSA and a group of controls. High-resolution structural 3 T MRI T1 and T2-weighted scans were used to estimate subcortical GM volumes and hippocampal subfields, and to perform vertex-wise analyses of cortical thickness and cortical surface area. We found that the presence of OSA was associated with a significant bilateral reduction in hippocampal volume, particularly in the CA1, CA3, and subicular regions, an effect specifically observed in PD patients and not in the control group. These findings suggest that the co-occurrence of OSA and PD may be related to early structural brain changes, highlighting the importance of timely OSA diagnosis and management to potentially delay cognitive decline in PD.

Background: Significant number of patients with Parkinson’s disease (PD) gradually progress to Parkinson’s disease dementia (PDD). Recent proposal for updating current diagnostic criteria for PDD recommends alternative screening tests and broader functional assessments. Objective: To evaluate the diagnostic concordance among algorithms for PDD based on Level I (i.e., screening) criteria and to assess their predictive validity for Level II (i.e., neuropsychological battery) diagnosis. Methods: A cross-sectional retrospective analysis of 190 patients with PD who underwent a comprehensive neuropsychological assessment. A total of 68 diagnostic algorithms were operationalized using combinations of scores derived from the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Functional impairment was based either on the Functional Assessment Questionnaire (FAQ) item 9 or the FAQ total score. Diagnostic concordance was evaluated using Cohen’s κ. Predictive validity for Level II classification was assessed using projection predictive variable selection. Results: Estimated PDD rates ranged from 2.1% up to 16.8%. Concordance was moderate to high among algorithms using the same functional impairment definition (κ FAQ total = 0.75, κ FAQ 9 = 0.86) but substantially lower when functional impairment definitions differed (κ = 0.43). A parsimonious screening model combining MoCA Five Words and MMSE Sevens adequately approximated Level II classification and yielded a prevalence-adjustable heuristic decision rule. Conclusions: Diagnostic outcomes for PDD are sensitive to the choice of cognitive and functional instruments suggesting that different algorithms may capture partially distinct constructs. Minimal screening using selected items can approximate Level II PDD diagnosis, but this simplification entails a trade-off between sensitivity and specificity.

BackgroundIn prior research, the Digital Assessment of Cognition (DAC), a brief digitally administered neuropsychological protocol that assesses verbal episodic memory, verbal working memory, and language, has been used to classify a small sample of memory clinic patients (n = 77) into four meaningful clinical groups.ObjectiveThe current research sought to extend these findings with a considerably larger sample.MethodsThe DAC was administered to 179 ambulatory care/memory clinic patients (45.30% female; 91.10% Caucasian). A comprehensive analysis of DAC core outcome measures and behavior reflecting process/errors was undertaken. Traditional paper/pencil assessment was also obtained. Using Jak, Bondi criteria (2009), paper/pencil test results classified patients into five groups: cognitively unimpaired (CU; n = 74), subtle cognitive impairment (SCI; n = 21), amnestic mild cognitive impairment (aMCI; n = 21), combined dysexecutive/mixed MCI (dys/mxMCI; n = 22), and mild dementia (n = 41).ResultsThe aMCI group presented with many of the classic features consistent with amnesia, i.e., rapid forgetting, reduced free recall clustering, and profligate responding to recognition foils. Latency for correct recognition responding was slower for aMCI compared to the CU group and appears to be associated with a neurocognitive network measuring both memory and language-related operations. SCI and dys/mxMCI groups tended to produce more perseverations on working memory test trials; and produced lower scores on DAC executive outcome measures that assessed auditory span and semantic fluency.ConclusionsThese findings support the criterion and construct validity of the DAC. When brought to scale the DAC could be an effective tool to assess for emergent MCI and dementia syndromes.

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. 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. 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. 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.

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.

Both Alzheimer's (AD) and Parkinson's disease (PD) are often associated with memory dysfunction, but their pathophysiological underpinnings differ. The current research aimed to differentiate specific profiles of memory impairment due to AD versus PD. We used controlled learning and cued recall paradigm based on the Memory Binding Test (MBT) in 'clinically cognitively normal' controls (CN; n = 161), in patients with amnestic mild cognitive impairment due to AD (AD-aMCI; n = 50) and due to PD (PD-MCI; n = 22), and in PD with normal cognition (n = 18) as based on performance in the neuropsychological battery to prevent circularity in diagnostic decision-making. We applied analysis of covariance (ANCOVA) and Receiver Operating Characteristic (ROC) analysis to determine between-group differences and detection potential of the MBT. We found statistically large between-group differences with worse memory performance in paired cued recall conditions in AD-aMCI .050). The detection potential of MBT paired cued recall for differentiating memory impairment in AD-aMCI from CN yielded an AUC of 90% (95% CI, 85-96) and an AUC of 91% (95% CI, 81->99) between AD-aMCI and PD-MCI. Associative memory and binding impairment are most pronounced in AD-aMCI in comparison to PD-MCI and controls. Overall, the MBT is an efficient tool for the differential diagnosis of memory impairment due to the two most common neurodegenerative diseases.

BACKGROUND:Cognitive impairment in Parkinson's disease (PD) is a well-established non-motor complication that significantly affects the quality of life and well-being of both patients and care partners. To optimally detect mild cognitive impairment or dementia, extensive neuropsychological assessment is essential. A wide range of cognitive tests and clinical outcome assessments have been used in clinical settings, often without regard to their clinimetric quality. METHODS:We performed a literature review of tests assessing attention/working memory and executive domains in PD (tests on other domains are included in an accompanying review). The selected tests were evaluated for their clinimetric properties and categorized by a panel of experts as "recommended," "recommended with caveats," "suggested," or "listed" according to the International Parkinson and Movement Disorder Society Clinical Outcome Assessment Scientific Evaluation Committee guidelines. RESULTS:A total of 30 tests were reviewed. Eight tests were "recommended," including four tests assessing attention/working memory abilities (WAIS-IV Digit Span, Coding and Symbol Search subtests, and Trail Making Test) and four tests assessing executive abilities (WAIS-IV Similarities, Wisconsin Card Sorting Test, Fluency Tests, and Stroop Color-Word Test). These tests demonstrated good to excellent levels of reliability and validity, have normative datasets, and are sensitive to change. Eight other tests were "recommended with caveats", eleven were "suggested," and three were "listed." CONCLUSIONS:The recommended tests for attention/working memory and executive functioning in PD can guide PD cognitive assessment. Other tests were identified as potentially useful; however, caution is advised due to their clinimetric limitations. Further validation studies are required for these tests. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Isolated REM sleep behavior disorder (iRBD) is associated with impaired colour discrimination, cognitive deficits and morphological changes. This study evaluates whether colour discrimination deficits in iRBD are mediated by cognitive functions or related to dopaminergic denervation and brain morphology. A sample of 73 patients with iRBD and 77 controls underwent neuropsychological assessment, and colour discrimination assessment using the Farnsworth Munsell 100 Hue Test, DAT-SPECT, and MRI. The data were analyzed using multiple regression, mediation analysis, and voxel-based morphometry. Significant between-group differences were found in total colour discrimination as well as in the red-yellow spectrum. The association between iRBD and performance in the yellow-green spectrum was mediated by cognitive functions, as measured by the Montreal Cognitive Assessment. In controls, a positive correlation between the yellow-green spectrum and the left inferior frontal gyrus was observed compared to patients, however, this association was largely driven by a single data point. The performance in the green–blue spectrum was associated with the activity of dopamine transporters in the caudate nucleus. No interactions were found for total colour discrimination in any analysis. The present findings demonstrate a colour vision deficit in iRBD, which is not directly linked to any of the proposed potential explanatory mechanisms.

BACKGROUND:Cognitive impairment in Parkinson's disease (PD) is a key non-motor complication during the disease course. OBJECTIVES:A review of detailed cognitive instruments to detect mild cognitive impairment (PD-MCI) or dementia (PDD) is needed to establish optimal tests that facilitate diagnostic accuracy. METHODS:We performed a systematic literature review of tests that assess memory, language including premorbid intelligence, and visuospatial domains (for tests of attention and executive functions see accompanying review) to determine suitability to assess cognition in PD. Based on in-depth scrutiny of psychometric and other relevant clinimetric properties, tests were rated as "recommended," "recommended with caveats," "suggested," or "listed" by the International Parkinson and Movement Disorder Society (IPMDS) panel of experts according to the IPMDS Clinical Outcome Assessment Scientific Evaluation Committee guidelines. RESULTS:We included 39 tests encompassing 48 outcome measures. Seven tests (different versions or subtests of the test counted once) were recommended, including four for memory, one for visuospatial domains, one for language (including three measures), and one for estimated premorbid intelligence. Furthermore, 10 tests (12 measures) were "recommended with caveats," 11 were "suggested," and 11 (15 measures) were "listed." CONCLUSIONS:Recommended neuropsychological tests in memory, visuospatial functions, and language are proposed to guide the assessment of cognitive impairment and its progression in PD-MCI and PDD, and for use in clinical trials to stratify participants or as outcome measures. Novel measures being developed will need extensive validation research to be "recommended." © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective This study investigated the prognostic utility of repeated olfactory testing in patients with isolated REM sleep behavior disorder (iRBD) for predicting phenoconversion to overt α-synucleinopathies. Methods We analyzed 59 iRBD patients (mean age: 66.9 ± 7.2 years; 91.5 % male) who underwent olfactory testing using the University of Pennsylvania Smell Identification Test at baseline and at a two-year follow-up. Patients were classified into persistent hyposmia, persistent normosmia, or unstable olfactory function groups. Clinical, cognitive, and dopamine transporter single photon emission CT (DAT-SPECT) parameters were assessed longitudinally. Results Olfactory function remained stable in most patients. The persistent hyposmia group (n = 37, 62.7 %) exhibited higher age, worse DAT-SPECT indices, and significant progression in MDS-UPDRS III over two years. In contrast, the persistent normosmia group (n = 11, 18.6 %) showed no significant neurodegenerative changes and had a 0 % phenoconversion rate over ∼5 years. Phenoconversion occurred in 20.3 % of patients, predominantly among those with persistent hyposmia (9/12 converters) and in patients from the unstable olfactory group (3/12 converts). While baseline hyposmia alone did not predict phenoconversion, repeated hyposmia significantly increased the risk (p < 0.05). Conclusion Repeated olfactory testing improves risk stratification in iRBD. Persistent normosmia is associated with a lower risk of phenoconversion, whereas persistent hyposmia predicts neurodegeneration. Serial olfactory assessments may serve as a cost-effective tool for identifying high-risk patients and refining recruitment for neuroprotective trials.

Aim: The Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in adults with reference standards for the Czech population. The MoCA-22 variant is designed for individuals with visual impairment or upper limb immobility and can be administered over the telephone. This study presents the Czech MoCA-22 normative standards. Materials and methods: The sample (N = 1,049) consists of participants from four studies conducted in the Czech Republic. The subjects included were aged 19- 98 years, and were without neurodegenerative, psychiatric, or other serious illness. Data for the MoCA-22 were derived from data obtained by the standard version of MoCA. Following established clinical practice and statistical analysis, the population and derived norms are divided into three age categories: 19- 50 years, 51- 74 years, and 75 years and older. Results: For these age categories above, which were further subdivided by educational status (lower, higher), we present mean scores and estimated percentile thresholds. Performance in the MoCA-22 is affected by demoraphic factors, such as educational status and age but not sex, as reflected by the regression equation. Conclusions: Normative data for MoCA-22 will complement the clinical armamentarium in Czechia and allow adequate cognitive screening in people whose health status limits them when using standard methods.

Background: Early identification of cognitive decline is crucial for diagnosing neurocognitive disorders at a stage when interventions may be most effective. Longitudinal neuropsychological assessment plays a key role in this process. However, distinguishing genuine cognitive decline from normal age-related variability remains a significant clinical challenge. Objective: This study aimed to provide Reliable Change Indices (RCIs) and regression-based models for evaluating cognitive trajectories using the Czech version of the Uniform Data Set 2.0 (UDS 2.0) neuropsychological battery, enhanced with additional tests. Methods: Based on a longitudinal study of 197 cognitively normal older adults, we computed various RCIs, alongside logistic regression models predicting follow-up scores from baseline data and demographic variables. Results: Significant practice effects with small effect sizes were found only for a subset of tests, while other measures remained stable over time. Regression-based models allow for a nuanced interpretation of individual change trajectories, with baseline score being the most consistent predictor. Conclusions: The provided indices and statistical tools support clinicians in making data-driven decisions regarding cognitive changes in individual patients. These findings enhance the clinical utility of neuropsychological assessments and may contribute to the early detection of pathological cognitive decline, including Alzheimer's disease-related decline.

Objectives: To analyze REM sleep without atonia (RWA) metrics in patients with isolated REM sleep behavior disorder (iRBD), Parkinson's disease (PD) and healthy subjects and compare them in terms of degree of presumed brainstem damage. Methods: Forty-nine iRBD patients, 62 PD patients and 38 healthy controls were included into the analysis. Detailed polysomnographic and clinical data including motor, olfactory, autonomic, and cognitive assessment were obtained in all participants and subsequently compared within groups without RBD (i.e., healthy controls, PD-RBD-) and with RBD (i.e., iRBD, PD-RBD+). SINBAR criteria were used to score RWA. Results: Twenty-one PD patients (33.8 %) had RBD. When comparing PD-RBD-patients and controls, RWA tonic (p = 0.001) and RWA mixed (p = 0.03) were higher in PD-RBD-group. PD-RBD-patients had worse olfactory function than controls (p < 0.001); no significant difference in autonomic or cognitive function was registered. There were no significant differences in RWA parameters when comparing iRBD and PD-RBD + groups. iRBD patients had better olfactory function than PD-RBD+ (p = 0.006); no significant difference in autonomic or cognitive function was registered. PD-RBD + had worse autonomic (p = 0.006) and olfactory (p = 0.001) but not motor and cognitive function compared to PD-RBD-. Conclusions: Untreated de-novo PD patients without RBD have increased RWA metrics compared to healthy subjects indicating subclinical degeneration of brainstem nuclei responsible for RWA. iRBD patients do not differ in RWA metrics from untreated de-novo PD patients with premotor RBD suggesting a similar level of brainstem degeneration caudal to substantia nigra in both groups. Groups with RBD are associated with autonomic dysfunction.

IntroductionA rapid and reliable neuropsychological protocol is essential for the efficient assessment of neurocognitive constructs related to emergent neurodegenerative diseases. We developed an AI-assisted, digitally administered/scored neuropsychological protocol that can be remotely administered in ~10 min. This protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illnesses.MethodsThe protocol was administered to 77 ambulatory care/memory clinic patients (56.40% women; 88.50% Caucasian). The protocol includes a 6-word version of the Philadelphia (repeatable) Verbal Learning Test [P(r)VLT], three trials of 5 digits backward from the Backwards Digit Span Test (BDST), and the “animal” fluency test. The protocol provides a comprehensive set of traditional “core” measures that are typically obtained through paper-and-pencil tests (i.e., serial list learning, immediate and delayed free recall, recognition hits, percent correct serial order backward digit span, and “animal” fluency output). Additionally, the protocol includes variables that quantify errors and detail the processes used in administering the tests. It also features two separate, norm-referenced summary scores specifically designed to measure executive control and memory.ResultsUsing four core measures, we used cluster analysis to classify participants into four groups: cognitively unimpaired (CU; n = 23), amnestic mild cognitive impairment (MCI; n = 17), dysexecutive MCI (n = 23), and dementia (n = 14). Subsequent analyses of error and process variables operationally defined key features of amnesia (i.e., rapid forgetting, extra-list intrusions, profligate responding to recognition foils); key features underlying reduced executive abilities (i.e., BDST items and dysexecutive errors); and the strength of the semantic association between successive responses on the “animal” fluency test. Executive and memory index scores effectively distinguished between all four groups. There was over 90% agreement between how cluster analysis of digitally obtained measures classified patients compared to classification using a traditional comprehensive neuropsychological protocol. The correlations between digitally obtained outcome variables and analogous paper/pencil measures were robust.DiscussionThe digitally administered protocol demonstrated a capacity to identify patterns of impaired performance and classification similar to those observed with standard paper/pencil neuropsychological tests. The inclusion of both core measures and detailed error/process variables suggests that this protocol can detect subtle, nuanced signs of early emergent neurodegenerative illness efficiently and comprehensively.

Přehledový článek se zaměřuje na diagnostiku, klinický obraz a terapii toxických psychóz, jejichž prevalence zaznamenala v posledních dekádách významný nárůst vázaný na značné zvýšení výroby a spotřeby psychoaktivních látek. Jedná se o druh poruch duševních i poruch chování způsobených užíváním psychoaktivních látek, jejichž následkem vzniká sekundární psychóza. Diferenciální diagnostika se zaměřuje zejména na rozlišení příznaků toxické psychózy od schizofrenie, kde se zejména pozitivní symptomatologie může překrývat. Vzhledem k heterogennosti skupiny toxických psychóz se článek zaměřuje dále na rozlišení jednotlivých forem dle vyvolávající psychoaktivní substance včetně jejich terapie.