Leistungsbasierte Beurteilung der Progredienz kognitiv bedingter Einschränkungen der Aktivitäten des täglichen Lebens bei der Parkinson-Erkrankung

Die Parkinson-Erkrankung (PD) ist eine neurodegenerative Erkrankung, bei welcher neben der charakteristischen Bewegungsstörung oftmals eine Vielzahl nicht-motorischer Symptome auftreten. Insbesondere im späten Krankheitsverlauf entwickeln PD-Patienten oftmals eine Parkinson-Demenz (PD-D). Für die Diagnose der PD-D sind kognitiv bedingte Einschränkungen der Aktivitäten des täglichen Lebens (ADL), die zu einer bedeutsamen Beeinträchtigung des täglichen Lebens führen, obligat. Aktuell ist die Entwicklung kognitiv bedingter ADL-Einschränkungen im Prodromalstadium der PD-D wenig erforscht. Studien weisen jedoch darauf hin, dass leistungsbasierte Tests geeignet sind, um leichte ADL-Einschränkungen im Prodromalstadium der PD-D zu erfassen. Ziel dieser Arbeit war es, die Progredienz kognitiv bedingter Einschränkungen der ADL-Funktion im Krankheitsverlauf der PD-D zu untersuchen. In die Langzeitstudie wurden 131 PD-Patienten der Abteilung für Neurologie mit Schwerpunkt Neurodegenerative Erkrankungen des Universitätsklinikums Tübingen und Kooperationspartner in die Studie eingeschlossen, 73 PD-Patienten nahmen nach durchschnittlich 3 Jahren an einer Folgeuntersuchung (FU-Untersuchung) teil. Neben der Erhebung demographischer Daten und klinischer Parameter (z. B. Motorik mittels Unified Parkinson’s Disease Rating Scale-III, Depressivität anhand des Beck-Depressions-Inventar) wurde der Multiple Object Test (MOT) als leistungsbasiertes Testverfahren zur Beurteilung der ADL-Funktion herangezogen. Die Testleistung im MOT wurde anhand einer standardisierten Bewertung von fünf Alltagsaufgaben quantitativ (Gesamtbearbeitungszeit, Gesamtfehleranzahl) und qualitativ (Desorientierungs-, Auslassungs-, Fehlplatzierungs-, Fehlgebrauchs-, Reihenfolge- und Ungeschicklichkeitsfehler) beurteilt. Die durchgeführte neuropsychologische Testbatterie zur Klassifikation der kognitiven Leistung beinhaltete Tests zur Prüfung der allgemeinen kognitiven Fähigkeit (z. B. Parkinson Neuropsychometric Dementia Assessment) sowie spezifische Verfahren zur Erfassung der Leistung in den kognitiven Domänen Exekutivfunktion (z. B. Trail Making Test B der Consortium to Establish A Registry for Alzheimer’s Disease (CERAD) Testbatterie), Aufmerksamkeit (z. B. Zahlenspannen rückwärts der Wechsler Memory Scale-Revised Edition (WMS-R)), Erinnerung und Gedächtnis (z. B. Wortliste Abrufen der CERAD Testbatterie), Praxis und Wahrnehmung (z. B. Figuren Abzeichen der CERAD Testbatterie) sowie Psychomotorik und Sprache (z. B. Semantische Flüssigkeit der CERAD Testbatterie). Entsprechend ihren neuropsychologischen Testergebnissen wurden die Studienteilnehmer entweder als PD ohne kognitive Störung (PD-noCI, n=39) oder mit kognitiver Störung (PD-CI, n=34; davon 8 mit PD-D) klassifiziert. Die statistische Auswertung der Daten zwischen den Studiengruppen (z.B. PD-noCI vs. PD-CI) erfolgte anhand nicht-parametrischer Verfahren und der binär logistischen Regression. Die Korrelationsanalysen basieren auf dem Rangkorrelationskoeffizient nach Spearman. Es konnte eine signifikante Zunahme der Gesamtfehleranzahl (p=0,001), der Gesamtbearbeitungszeit (p<0,001) und der Anzahl an Desorientierungs- (p=0,035) und Auslassungsfehlern (p<0,001) in der Gesamtkohorte im Verlauf von drei Jahren gezeigt werden. Die im MOT erfassten ADL-Einschränkungen im Studienverlauf (Differenzwerte FU - BL) waren mit Veränderungen der Kognition über die Zeit, insbesondere Tests der Praxis und Wahrnehmung, assoziiert. In der Gruppe PD-CI konnte im Vergleich zur Gruppe PD-noCI eine signifikant höhere Gesamtfehleranzahl (p<0,011), Gesamtbearbeitungszeit (p<0,011) und Anzahl an Desorientierungsfehlern (p<0,010) zu beiden Untersuchungszeitpunkten festgestellt werden. Patienten mit PD-CI hatten im Vergleich zu PD-noCI eine stärkere Zunahme an Auslassungsfehlern zwischen den beiden Studienvisiten (p=0,028). Die Ergebnisse zeigen, dass der MOT ein valides Verfahren zur Erfassung kognitiv bedingter ADL-Einschränkungen ist und zwischen der ADL-Leistung von PD-noCI und PD-CI differenzieren kann. Kognitiv bedingte ADL-Defizite treten in milder Ausprägung bereits in der Prodromalphase der PD-D auf und sind im Krankheitsverlauf progredient. Insbesondere Auslassungsfehler scheinen mit dem kognitiven Status bei der PD assoziiert zu sein

Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy:A Bayesian Approach

Background: Cognitive decline is a key outcome of clinical studies in Alzheimer’s disease (AD). Objective: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. Methods: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. Results: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. Conclusions: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid

Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach

Background: Cognitive decline is a key outcome of clinical studies in Alzheimer's disease (AD). Objective: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. Methods: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. Results: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. Conclusions: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid

The comorbidity profiles and medication issues of patients with multiple system atrophy:a systematic cross-sectional analysis

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management.OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients.METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®.RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue.CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.</p

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.ObjectivesTo explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.MethodsCross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik (R).ResultsIn total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions.ConclusionsPSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients

The Multiple Object Test as a performance-based tool to assess the decline of ADL function in Parkinson’s disease

<div><p>Introduction</p><p>As cognitive-driven worsening of activities of the daily living (ADL) in Parkinson’s disease (PD) is the core feature of PD dementia (PDD), there is great need for sensitive quantitative assessment. Aim of our study was the evaluation of cognitive-driven worsening of ADL by the performance-based Multiple Object Test (MOT), offering an essential clinical advantage as it is quick and easy to apply in a clinical context even on severely impaired patients.</p><p>Methods</p><p>73 PD patients were assessed longitudinally over a period of 37 (6–49) months. According to their neuropsychological profile the sample was divided into two groups: PD patients with (n = 34, PD-CI) and without cognitive impairment (n = 39, PD-noCI). The MOT comprises five routine tasks (e.g. to make coffee) quick and easy to apply. Quantitative (total error number, processing time) and qualitative parameters (error type) were analyzed using non-parametric test statistic (e.g.Wilcoxon signed-rank test, binary logistic regression).</p><p>Results</p><p>Median number of total errors (p = 0.001), processing time (p<0.001), perplexity (p = 0.035), and omission errors (p<0.001) increased significantly from baseline to follow-up in the total sample. Worsening of MOT performance was correlated to cognitive decline in the attention/ executive function and visuo-constructive domain. PD-CI showed an increase in omission errors (p = 0.027) compared to PD-noCI over time. This increase in omission errors between visits was further identified as a risk marker for PDD conversion.</p><p>Conclusion</p><p>The MOT, especially frequency of omission errors, is a promising tool to rate PD patients objectively and might help to identify patients with a high risk for having mild cognitive impairment or dementia.</p></div

Baseline characteristics of the follow-up cohort, and between-group comparison of Parkinson’s disease patients with (PD-CI) and without (PD-noCI) cognitive impairment.

<p>Baseline characteristics of the follow-up cohort, and between-group comparison of Parkinson’s disease patients with (PD-CI) and without (PD-noCI) cognitive impairment.</p

Progression of qualitative MOT parameters.

<p>Comparison of change values (follow-up–baseline) in each Multiple Object Test (MOT) error category between PD patients with (PD-CI) and without (PD-noCI) cognitive impairment.</p

Cognitive diagnosis of patients at baseline and follow-up.

<p>Cognitive diagnosis of patients at baseline and follow-up.</p