Post-Cueing Deficits with Maintained Cueing Benefits in Patients with Parkinson's Disease Dementia

In Parkinson's disease (PD), internal cueing mechanisms are impaired leading to symptoms like hypokinesia. However, external cues can improve movement execution by using cortical resources. These cortical processes can be affected by cognitive decline in dementia. It is still unclear how dementia in PD influences external cueing. We investigated a group of 25 PD patients with dementia (PDD) and 25 non-demented PD patients (PDnD) matched by age, sex, and disease duration in a simple reaction time task using an additional acoustic cue. PDD patients benefited from the additional cue in similar magnitude as did PDnD patients. However, withdrawal of the cue led to a significantly increased reaction time in the PDD group compared to the PDnD patients. Our results indicate that even PDD patients can benefit from strategies using external cue presentation but the process of cognitive worsening can reduce the effect when cues are withdrawn

Psychopathological symptoms of depression in Parkinson's disease compared to major depression

Parkinson's disease is frequently associated with depressive symptoms. When depression occurs at early stages and before the onset of characteristic motor symptoms of the disease, differential diagnosis of major depression may be difficult. Differences in psychopathological features of depression in Parkinson's disease and major depression have been reported by some authors. This study presents data of 49 patients with depression in Parkinson's disease and 38 patients with major depression. Severity of depressive symptoms was equivalent in both groups. Depressive features did not differ between the two groups with exception of affective flattening, delusional ideas and suicide attempts. In conclusion, this investigation gives support to the assumption of a common neurobiological origin of depression in Parkinson's disease and major depression

LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol:Deep Phenotyping of an International Genetic Cohort

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions.Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants.Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021).Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivityClinical Trial Registration:ClinicalTrials.gov, NCT04214509

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Benserazide-induced diarrhea – A retrospective clinical study

Background: Although diarrhea has been reported as a side effect of L-3,4- dihydroxyphenylalanine (L-DOPA)/benserazide, it is largely unknown and unrecognized, presumably because it is very rare. There is almost no literature on benserazide-induced diarrhea (BID), no pharmacological explanation and, crucially, no treatment recommendation. This can lead to physicians misdiagnosing BID, for example as colitis, and initiating misguided and ultimately ineffective drug treatments. Or it can lead to erroneous assumptions about a general intolerance and subsequent discontinuation of L-DOPA medication – for lack of a better solution – at the high price of living with the recurring symptoms of Parkinson’s disease. Thus, our study aims to fill these gaps, beginning with a treatment recommendation: A simple switch to LDOPA/ carbidopa has proven to be an effective solution in virtually all cases of BID, usually leading to full remission within days. Finding a possible pharmacological explanation was the next objective of this study. Methods: We retrospectively analyzed 50 case files of patients with BID, searching for patterns that could potentially explain this intolerance. Results: The most frequent concomitant disease was hypertension, likely due to high average age. Beta-blockers and acetylsalicylic acid were the most frequent concomitant medications. Otherwise, no conspicuous pattern emerged in this seemingly rather heterogeneous sample. Conclusions: Plasma protein binding (PPB) was suspected as a key difference between benserazide and carbidopa that might potentially explain why some patients can tolerate carbidopa but not benserazide. However, reports on PPB of carbidopa and benserazide vary wildly from one source to another, making definitive conclusions impossible

Psychopathological symptoms of depression in Parkinson\u27s disease compared to major depression

Parkinson\u27s disease is frequently associated with depressive symptoms. When depression occurs at early stages and before the onset of characteristic motor symptoms of the disease, differential diagnosis of major depression may be difficult. Differences in psychopathological features of depression in Parkinson\u27s disease and major depression have been reported by some authors. This study presents data of 49 patients with depression in Parkinson\u27s disease and 38 patients with major depression. Severity of depressive symptoms was equivalent in both groups. Depressive features did not differ between the two groups with exception of affective flattening, delusional ideas and suicide attempts. In conclusion, this investigation gives support to the assumption of a common neurobiological origin of depression in Parkinson\u27s disease and major depression

Clinical characteristics with an impact on ADL functions of PD patients with cognitive impairment indicative of dementia.

BACKGROUND: Dementia in Parkinson's disease (PD) is defined as cognitive decline severe enough to affect activities of daily living function (ADL). The aim of our exploratory study was to compare two groups of PD patients. Both groups had cognitive deficits severe enough to justify diagnosis of dementia, but they differed according to caregivers' rating on ADL dysfunction. Parameters which differed between the two groups were interpreted to affect the caregivers' perception of ADL dysfunction in PD patients with cognitive impairment indicative of Parkinson's disease dementia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty of 131 Parkinson's disease patients fulfilled the Movement Disorders Society Task Force - recommended, cognitive Level-I-criteria for dementia. According to standardized caregiver ratings, volunteers were grouped into 18 patients with (ADL-) and 12 without instrumental activities of daily living dysfunction (ADL+). Caregiver activities of daily living function ratings closely correlated with self-estimates of patients and those of physician (p<0.001). ADL- patients performed worse on tests assessing visual-construction (p<0.05) and attention (p=0.03) than ADL+ patients. Moreover, the postural instability and gait disorder subtype was more frequent in ADL- patients (p=0.009). ADL- patients tended to have more communication problems (p=0.05), more anxiety (p=0.05) and showed a tendency to be treated more often with neuroleptics (p=0.049) than ADL+. CONCLUSIONS/SIGNIFICANCE: Results indicate that worse attention, visual-construction abilities, the postural instability and gait disorder subtype, communication problems, medication and presence of anxiety are related to activities of daily living dysfunctions in Parkinson's disease patients with cognitive decline indicative of dementia. Our data suggests that not only cognitive factors but also non-cognitive factors seem to be linked to the diagnosis of Parkinson's disease dementia associated with significant impact on instrumental activities of daily living function. Further studies with larger sample sizes are needed to verify our results

Genetische Untersuchungen beim Parkinson-Syndrom: Indikation und praktische Durchführung

Zusammenfassung Seit der Erstbeschreibung einer monogenetischen Ursache der Parkinson-Erkrankung sind mehr als 20 Jahre vergangen. Trotz der Fortschritte der molekulargenetischen Diagnostik wird diese immer noch sehr selten durchgefuhrt. Genetische Untersuchungen bei Patienten mit Parkinson-Syndromen werden allerdings zukunftig einen gro ss en Stellenwert einnehmen. Dies ist nicht nur im Hinblick auf die Diagnosesicherung bei Parkinson-Patienten mit jungem Erkrankungsbeginn und/oder positiver Familienanamnese zu sehen, sondern auch im Rahmen der personalisierten Medizin mit neuen therapeutischen Moglichkeiten. Im Folgenden mochten wir einen uberblick uber die Grundlagen der genetischen Diagnostik, die gesetzlichen Voraussetzungen, das Vorgehen fur eine genetische Diagnostik und einen Ausblick in die Zukunft bei genetischen Parkinson-Erkrankungen geben. Abstract More than 20 years have passed since the first description of a monogenic cause of Parkinson's disease. Despite the tremendous advances of genetic testing these techniques are rarely used in Parkinson's disease. However, genetic tests in patients with Parkinson's syndrome will play an important role in the future. This is not only to ensure the diagnosis of Parkinson's patients with a young onset and/or a positive family history, but also in the context of personalised medicine with new therapeutic options. In the following we would like to give an overview of the basics of genetic testing, the legal requirements, the procedure for genetic testing and an outlook into the future for hereditary Parkinson's diseases