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Motor–cognitive training in Parkinson’s disease (PD) can positively affect gait and balance, but whether motor–cognitive (dual-task) performance improves is unknown. This meta-analysis, therefore, aimed to establish the current evidence on the effects of motor–cognitive training on dual-task performance in PD. Systematic searches were conducted in five databases and 11 studies with a total of 597 people (mean age: 68.9 years; mean PD duration: 6.8 years) were included. We found a mean difference in dual-task gait speed (0.12 m/s (95% CI 0.08, 0.17)), dual-task cadence (2.91 steps/min (95% CI 0.08, 5.73)), dual-task stride length (10.12 cm (95% CI 4.86, 15.38)) and dual-task cost on gait speed (− 8.75% (95% CI − 14.57, − 2.92)) in favor of motor–cognitive training compared to controls. The GRADE analysis revealed that the findings were based on high certainty evidence. Thus, we can for the first time systematically show that people with PD can improve their dual-task ability through motor–cognitive training.

Background: Fear of progression (FoP) is a reactive, conscious concern about chronic disease progression and its consequences which may limit quality of life substantially. Only one study has examined FoP in Parkinson’s disease (PD), showing the second highest FoP scores among chronic diseases. Objective: To examine FoP prevalence and to exploratorily analyze determinants of FoP in PD. Methods: Within a multicenter cross-sectional study, 120 PD inpatients (age: 64.45±9.20; 60.8% male; UPDRS-III: 28.86±16.12) were examined with the FoP questionnaire (FoP-Q; max. 20 points). Stepwise multiple linear regression analysis examined sociodemographic, clinical, and (neuro-) psychological determinants of FoP. Results: With a mean FoP-Q score of 8.08±2.17, 63.0% of the patients were classified with moderate FoP and 17.6% with dysfunctional (i.e., severe) FoP. The highest scores were shown for the subscale ‘loss of autonomy’. Increased levels of anxiety, less self-efficacy, female gender, current employment, and lower health literacy were identified as significant determinants associated with FoP. Conclusion: With more than 80% of patients showing moderate to dysfunctional FoP, it must be regarded as a frequent symptom in PD, which needs to be further understood and addressed in clinical practice. Clinical parameters like PD duration and severity were no determinants for FoP, indicating that FoP awareness must be considered by professionals at all disease stages.

Background: Working memory (WM) training (WMT) is a popular intervention approach against cognitive decline in patients with Parkinson’s disease (PD). However, heterogeneity in WM responsiveness suggests that WMT may not be equally efficient for all patients. Objective: The present study aims to evaluate a multivariate model to predict post-intervention verbal WM in patients with PD using a supervised machine learning approach. We test the predictive potential of novel learning parameters derived from the WMT and compare their predictiveness to other more commonly used domains including demographic, clinical, and cognitive data. Methods: 37 patients with PD (age: 64.09±8.56, 48.6% female, 94.7% Hoehn & Yahr stage 2) participated in a 5-week WMT. Four random forest regression models including 1) cognitive variables only, 2) learning parameters only, 3) both cognitive and learning variables, and 4) the entire set of variables (with additional demographic and clinical data, ‘all’ model), were built to predict immediate and 3-month-follow-up WM. Result: The ‘all’ model predicted verbal WM with the lowest root mean square error (RMSE) compared to the other models, at both immediate (RMSE = 0.184; 95% -CI=[0.184;0.185]) and 3-month follow-up (RMSE = 0.216; 95% -CI=[0.215;0.217]). Cognitive baseline parameters were among the most important predictors in the ‘all’ model. The model combining cognitive and learning parameters significantly outperformed the model solely based on cognitive variables. Conclusion: Commonly assessed demographic, clinical, and cognitive variables provide robust prediction of response to WMT. Nonetheless, inclusion of training-inherent learning parameters further boosts precision of prediction models which in turn may augment training benefits following cognitive interventions in patients with PD.

Background: Previous reviews indicated positive effects of resistance training (RT) on motor outcomes in Parkinson’s disease (PD). However, inconsistencies between the included studies exist, and non-motor outcomes have only scarcely been considered in a review on RT in PD. Objective: To analyze the RT effects on motor- and non-motor outcomes in PD patients compared to passive and physically active control groups (i.e., other structured physical interventions). Methods: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials of RT in PD. After identifying 18 studies, a meta-analysis was conducted for the outcomes muscle strength, motor impairment, freezing of gait (FoG), mobility and balance, quality of life (QoL), depression, cognition, and adverse events. Meta-analyses with random models were calculated using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). Results: When comparing RT with passive control groups, the meta-analyses showed significant large effects on muscle strength (SMD = –0.84, 95% CI –1.29––0.39, p = 0.0003), motor impairment (SMD = –0.81, 95% CI –1.34––0.27, p = 0.003), mobility and balance (MD = –1.81, 95% CI –3.13––0.49, p = 0.007), and small significant effects on QoL (SMD = –0.48, 95% CI –0.86––0.10, p = 0.01). RT compared with physically active control groups reached no significant results for any outcome. Conclusions: RT improves muscle strength, motor impairment, mobility and balance, QoL, and depression in PD patients. However, it is not superior to other physically active interventions. Therefore, exercise is important for PD patients but according to this analysis, its type is of secondary interest.

Background: Visuo-cognitive impairment is common in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI) and constitutes a prognostic factor for the conversion to Parkinson’s disease dementia (PDD). However, systematic analyses on which neuropsychological tests are most suitable to assess visuo-cognition in PD-MCI and PDD and to differentiate these cognitive stages are lacking. Objective: To review neuropsychological tests used to assess visuo-cognition including visuo-perceptual and visuo-spatial processing, visuo-constructive copying and drawing on command abilities; and to identify the visuo-cognitive subdomain as well as tests most suitable to discriminate between PD-MCI and PDD. Methods: MEDLINE, PsycINFO, Web of Science Core Collection, and CENTRAL were systematically searched for relevant studies assessing visuo-cognitive outcomes in patients with PD-MCI and PDD. Risk of bias was assessed using a customized form based on well-established tools. Random-effect meta-analyses were conducted. Results: 33 studies were included in the systematic review. Data of 19 studies were entered in meta-analyses. Considerable heterogeneity regarding applied tests, test versions, and scoring systems exists. Data indicate that visuo-constructive command tasks are the subdomain best suited to discriminate between PD-MCI and PDD. Furthermore, they indicate that the Rey-Osterrieth-Complex-Figure Test (ROCF), Corsi Block-Tapping Test, Judgment of Line Orientation (JLO), and Clock Drawing Test (CDT) are tests able to differentiate between the two stages. Conclusion: We provide suggestions for suitable visuo-cognitive tests (Corsi Block-Tapping Test, or JLO, ROCF, CDT) to improve diagnostic accuracy. Methodological challenges (e.g., heterogeneity of definitions, tests) are discussed and suggestions for future research are provided. Registration: https://www.crd.york.ac.uk/prospero/, ID: CRD42018088244

Cognitive impairment in Parkinson's disease (PD), especially in patients with mild cognitive impairment (PD-MCI), coincides with less physical activity. Cognitive trainings (CT) have been found to promote laboratory environment-based movement. Knowledge about their effect in natural home-based environment, reflecting everyday function, is sparse. This explorative study investigated short-term effects of CT on physical activity assessed by home-based accelerometry, and its relation to change of cognitive function over time and non-cognitive outcomes in patients with PD-MCI. Cognitive and non-cognitive correlates of movement parameters at pretest were evaluated as well.Eighteen patients with PD-MCI of the TrainParC study were analyzed. Those patients received either a 6-week multidomain group CT or physical training (PT). Physical activity and sedentary behavior were assessed with wearable accelerometers worn up to seven days pre- and post-training.Patients in the CT group displayed significantly greater increases in active periods after training than patients assigned to PT. In the CT group, increases in executive functioning were associated with increases in active periods and decreases in active mean bout length after training. At pretest, reduced working memory correlated with longer sedentary mean bout length, and impairment in activities of daily living (ADL) correlated with a higher number of sedentary periods.Study data revealed that CT can increase physical activity in patients with PD-MCI, possibly due to effects on executive functions, which needs further investigation in larger sample sizes. Lower working memory performance and ADL impairment might be associated with a more inactive lifestyle in patients with PD-MCI.

Introduction The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. Objective The aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. Methods Baseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. Results The newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). Conclusion Results suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.

ZusammenfassungDie überwiegende Anzahl bisheriger Studien zu Apraxien fokussiert die Rolle der linken Hemisphäre (LH), obwohl im klinischen Alltag apraktische Defizite auch bei Patienten mit rechtshemisphärischen Schlaganfällen (RH) beobachtet werden. Daher wurden in der aktuellen Untersuchung die Prävalenz und Ausprägung apraktischer Defizite bei Patienten mit linkshemisphärischen (n = 66) und rechtshemisphärischen (n = 73) Schlaganfällen verglichen, nachdem für Alter und sprachliche Leistung kontrolliert worden war.Unter Anwendung dieser Kontrollvariablen ergab sich kein signifikanter Unterschied zwischen den linkshemisphärisch und rechtshemisphärisch betroffenen Patienten bei der Imitation von Handpositionen. Übereinstimmend mit früheren Berichten schnitten die Patienten mit rechtshemisphärischen Schlaganfällen aber bei der Imitation der Fingerkonstellationen schlechter ab. Interessanterweise zeigten die rechtshemisphärisch betroffenen Patienten auch geringere Leistungen bei den bukkofazialen Items des Kölner Apraxie Screenings (KAS), vornehmlich bei Gesten der oberen Gesichtshälfte. Für beide Patientengruppen wirkten sich sprachliche Auffälligkeiten mehr auf die Pantomime- als auf die Imitationsleistungen beeinträchtigend aus.Die Ergebnisse legen nahe, dass nach der Kontrolle für Alter und sprachliche Leistungen die Prävalenz und Ausprägung apraktischer Defizite bei Patienten mit rechts- und linkshemisphärischen Schlaganfällen nicht signifikant unterschiedlich sind und in den jeweiligen Rehabilitationsprogrammen entsprechend berücksichtigt werden sollten.

Background: Parkinson’s disease (PD) has been associated with a tendency towards more risky decisions. However, the commonly used paradigms typically neglect the social context. Objective: Here, we investigated social decision-making and self-estimation in a competitive experimental task. Methods: A computerized experimental setting was used in which 86 PD patients (age = 66.5 [50–79], 62.8% male, H&Y = 2 [1.5–3]) and 44 healthy controls (HC; age = 67 [54–79], 54.4% male) in groups of four performed mathematical addition tasks in which they were asked to calculate as many sums as possible in five minutes. Participants had to choose their preferred compensation scheme (“piece rate” versus “tournament”) and retrospectively rank their performance in comparison to the suspected performance of the others. A comprehensive neuropsychological test battery was also conducted. Results: No significant difference was found in overall social decision-making and self-estimation between PD patients and HC. However, for those individuals who made inadequate decisions, PD patients engaged in significantly more risk-averse and HC in more risky decisions. Concerning those inadequate decisions, the PD patients made more extreme decisions (severity of social decision-making) in both directions (risk-averse, risk-seeking). Conclusion: Our data indicate that social decision-making behavior and self-estimation are largely intact in PD patients with mild to moderate disease stages and intact global cognition, executive functions, and social cognition. Future studies with more heterogeneous PD samples regarding their neuropsychological profile will have to examine at which state social decision-making may be affected and by which factors this behavior might be influenced.

Background Subjective cognitive decline (SCD) may occur very early in the course of Parkinson’s disease (PD) before the onset of objective cognitive decline. Data on neural correlates and determinants of SCD in PD are rare. Objective The aim of the present study was to identify neural correlates as well as sociodemographic, clinical, and neuropsychological predictors of SCD in patients with PD. Methods We retrospectively analyzed 30 patients with PD without cognitive impairment (23% female, 66.90 ± 7.20 years, UPDRS-III: 19.83 ± 9.29), of which n = 12 patients were classified as having no SCD (control group, PD-CG) and n = 18 as having SCD (PD-SCD). Neuropsychological testing and 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) were conducted. SCD was assessed using a questionnaire covering multiple cognitive domains. Results SCD subscores differed significantly between PD-CG and PD-SCD and correlated significantly with other scales measuring related concepts. FDG-PET whole-brain voxel-wise regression analysis revealed hypometabolism in middle frontal, middle temporal, and occipital areas, and the angular gyrus as neural correlates of SCD in PD. Next to this hypometabolism, depressive symptoms were an independent significant determinant of SCD in a stepwise regression analysis (adjusted R2 = 50.3%). Conclusion This study strengthens the hypothesis of SCD being an early manifestation of future cognitive decline in PD and, more generally, early pathological changes in PD. The early identification of the vulnerability for future cognitive decline constitutes the basis for successful prevention and delay of this non-motor symptom.

Recently, it was shown that patients with Parkinson's disease (PD) who exhibit an "Alzheimer's disease (AD)-like" pattern of brain atrophy are at greater risk for future cognitive decline. This study aimed to investigate whether this association is domain-specific and whether atrophy associated with brain aging also relates to cognitive impairment in PD. SPARE-AD, an MRI index capturing AD-like atrophy, and atrophy-based estimates of brain age were computed from longitudinal structural imaging data of 178 PD patients and 84 healthy subjects from the LANDSCAPE cohort. All patients underwent an extensive neuropsychological test battery. Patients diagnosed with mild cognitive impairment or dementia were found to have higher SPARE-AD scores as compared to patients with normal cognition and healthy controls. All patient groups showed increased brain age. SPARE-AD predicted impairment in memory, language and executive functions, whereas advanced brain age was associated with deficits in attention and working memory. Data suggest that SPARE-AD and brain age are differentially related to domain-specific cognitive decline in PD. The underlying pathomechanisms remain to be determined.

Deep Brain Stimulation (DBS) has been proven to alleviate motor symptoms in Parkinson's Disease (PD). Regarding non-motor symptoms, however, inconsistencies have been reported, on whether DBS causes reductions in well-being and functioning. To assess motor and non-motor impairment in DBS-patients, the Deep Brain Stimulation Impairment Scale (DBS-IS) has been developed. Yet, the extent to which the DBS-IS detects impairment in DBS-patients and thus could serve as a useful tool that complements the PDQ-39 (gold standard) in assessment of well-being and functioning in PD-patients has not been shown.By comparing DBS and non-DBS-patients we aimed to identify DBS-specific symptoms. We thereby aimed to show in how far the DBS-IS complements the PDQ-39 in assessing well-being and functioning in PD patients under DBS.In a cross-sectional study, 186 DBS-patients were matched (for age, disease duration and sex) to 186 non-DBS-patients (N = 372) and the two groups were compared regarding well-being and functioning: Impairment was assessed via DBS-IS and overall Quality of Life (QoL) was assessed via PDQ-39. Additionally, we analyzed differences in impairment between age and disease duration clusters.DBS-patients showed significantly higher total impairment (DBS-IS) and significantly higher impairment on the subscales Postural Instability and Gait difficulties and speaking difficulties than non-DBS-patients. Impairment increased with age and disease duration and, overall, differences in impairment rose by age. Overall QoL (PDQ-39) was non-significantly lower in DBS-patients.Since there is evidence that the PDQ-39 misses some DBS-specific symptoms, the DBS-IS is recommended to complement the PDQ-39 when assessing DBS-patients.

Zusammenfassung Hintergrund Die Erfassung der Alltagsaktivitäten (Activities of Daily Living, ADL) stößt im Rahmen der Demenzdiagnostik bei Menschen mit Migrationshintergrund auf Grenzen, da bisherige Skalen sprachliche, bildungsspezifische, kulturell-religiöse und Lifestyle-Faktoren kaum berücksichtigen. Ziel der Studie Ziel ist die Entwicklung der „Cologne Culture ADL“ (CC-ADL), die kulturell-religiöse Lifestyle-Aspekte sowie die zunehmende Digitalisierung im Alltag berücksichtigt und für deutsche und türkischstämmige Migrantinnen und Migranten geeignet ist. Methoden Zur Generierung von ADL-Items wurden qualitative Interviews (N = 15) mit kognitiv nicht eingeschränkten deutschen und türkischen Probanden geführt und eine erste Skalenversion des Instruments entwickelt, die erneut bei kognitiv nicht eingeschränkten deutschen (n = 197) und türkischen Probanden (n = 53) angewandt wurde. Auf Basis einer Itemanalyse entstand die gekürzte ADL-Skala, die Einschränkungen der „Kognition“, „Basic Activities of Daily Living (BADL)“ und „Instrumental Activities of Daily Living (IADL)“ erfragt – bei türkischen Probanden kommen Fragen zum muslimischen Gebet hinzu. Zum Ausschluss von kognitiven Störungen und Depressionen wurden der Montreal Cognitive Assessment (MoCA), die Geriatrische Depressionsskala (GDS) und zur Skalen-Validierung die Bayer-ADL angewandt. Ergebnisse Der Alltag von deutschen und türkischen Menschen unterschied sich in Aspekten der religiösen Alltagsgestaltung sowie im Hinblick auf kulturell-gesellschaftliche Aktivitäten, die in der CC-ADL berücksichtigt werden. Die Reliabilitätsanalyse bezüglich der internen Konsistenz ergab für die Subskalen: „Kognition“ (Deutsche α = .43; Türken α = .80); BADL (Deutsche α = .55; Türken α = −.04); IADL (Deutsche α = .91; Türken α = .83); Gebetsitems (Türken) α = .73. Die Korrelation des CC-ADL-Gesamtscores mit der Bayer-ADL beträgt für deutsche Personen ρ = .347 (p Schlussfolgerung Die Entwicklung dieser für Migranten geeigneten ADL-Skala kann eine wichtige Lücke in der Demenzdiagnostik schließen. Zur Entwicklung einer finalen Version der CC-ADL bedarf es weiterer Daten von kognitiv gesunden Probandinnen / Probanden und Patientinnen / Patienten (Mild Cognitive Impairment und Demenz).

Background Despite a growing research literature on caregiver burden in progressive diseases (e.g., dementia), the experiences and needs of family members of patients with Parkinson's disease (PD), especially of those who are not caring primarily, are underinvestigated. Furthermore, there is only limited evidence for interventions for PD relatives. Objective The aim of this cross-sectional study was to assess the intervention needs of PD family members. Methods 133 relatives of PD patients were asked about the essential topics and the appropriate format of a psychoeducational group intervention by means of a standardized questionnaire. Results The sample consisted of 67 caregivers (CG) and 66 non-caregivers (nCG). CGs and nCGs were mainly female (75% vs. 64%) and patients' spouses (97% vs. 59%). CGs were about 15 years older than nCGs. Both groups were considerably burdened by patients' disease, and 84% of the CGs and 90% of the nCGs were convinced about the subjective benefit of a group intervention. The majority of the CGs rated stress management, coping with emotional distress, receiving social support, and different information modules as essential topics. In comparison, more than half of the nCGs voted for sharing experiences with other relatives, as well as for different information modules. Most individuals preferred two-hour sessions in the late afternoon (once or twice a week) with a maximum of ten participants. Conclusions This study contributes to an increased understanding of PD families' needs and might inform future studies concerning the development of needs-based and low-threshold support programs.

Objective: Depressive symptoms have a high prevalence in patients with Parkinson's disease (PD) and are associated with cognitive dysfunction. Especially in PD with mild cognitive impairment (MCI), a time-efficient and valid instrument for the assessment of depression primarily focusing on psychological symptoms and disregarding confounding somatic symptoms is needed. We performed an examination of the psychometric properties of the Beck Depression Inventory II (BDI-II) and the Beck Depression Inventory Fast Screen (BDI-FS).Methods: The sample consisted of 64 patients [22 females and 42 males, mean age: 67.27 years (SD = 7.32)]. Depressive symptoms were measured in a cohort of PD patients with MCI. For the BDI-II and BDI-FS the psychometric concepts of internal consistency, convergent validity and diagnostic agreement were assessed.Results: Patients gave higher ratings on test items addressing somatic symptoms than those addressing non-somatic ones. The correlation between the absolute total scores of the BDI-II and the BDI-FS was significant (r = 0.91, p < 0.001), which indicated convergent validity. The Cronbach's alpha values indicated adequate internal consistencies for both measures (BDI-II: 0.84; BDI-FS: 0.78). There was a higher than chance level agreement of diagnoses of the two questionnaires, measured by Cohen's kappa (0.58, p < 0.001). The agreements between previous diagnosis of depression and the diagnoses of the BDI-II/BDI-FS were also significantly higher than chance level (BDI-II: 0.34, p = 0.007, BDI-FS: 0.39, p = 0.002). Additional AUC analysis across different cutoffs showed that performance of BDI-FS was better than BDI-II, supporting the observation of an equivalent or better performance of BDI-FS than BDI-II. Importantly, AUC analysis confirmed that a cutoff = 4 for BDI-FS was suitable in the considered sample of patients with PD-MCI.Discussion: In a cohort of PD-MCI, the BDI-FS demonstrates adequate psychometric properties in comparison to the BDI-II and can be used as a screening measure for assessing depression in cognitively impaired PD patients, focusing solely on psychological symptoms. Still, further research is needed to validate this instrument.

BACKGROUND: The negative impact of cognitive dysfunction on motor rehabilitation as a relearning-process is well known in stroke patients. However, evidence for combined cognitive and motor training (CMT) is lacking. OBJECTIVE: To evaluate the effects of combined CMT in early stroke rehabilitation. METHODS: In a controlled pilot study, 29 moderately affected stroke patients with low-level motor performance and cognitive impairment received motor therapy plus either cognitive (experimental group, EG) or low-frequency ergometer training (control group, CG) for eight days. RESULTS: Both groups improved their motor functioning significantly. After training, between-group comparison revealed significant differences for cognitive flexibility and trends for set-shifting, working memory, and reaction control in favor of the EG. Within-group effects showed improvement across all cognitive domains in the EG, which correlated with gains in bed-mobility, while the CG showed no significant improvement in cognition. Rather, a trend towards reaction control decline was observed, which correlated with less functional progression and recovery. Furthermore, a decline in cognitive flexibility, set-shifting, and working memory was descriptively observed. CONCLUSIONS: Combined CMT may enhance cognition and motor relearning early after stroke and is superior to single motor training. Further studies are needed to replicate these results and investigate long-term benefits.

Background Meta-analyses indicate positive effects of cognitive training (CT) in patients with Parkinson’s disease (PD), however, most previous studies had small sample sizes and did not evaluate long-term follow-up. Therefore, a multicenter randomized controlled, single-blinded trial (Train-ParC study) was conducted to examine CT effects in PD patients with mild cognitive impairment (PD-MCI). Immediately after CT, an enhancement of executive functions was demonstrated. Here, we present the long-term results 6 and 12 months after CT. Methods At baseline, 64 PD-MCI patients were randomized to a multidomain CT group (n = 33) or to a low-intensity physical activity training control group (PT) (n = 31). Both interventions included 90 min training sessions twice a week for 6 weeks. 54 patients completed the 6 months (CT: n = 28, PT: n = 26) and 49 patients the 12 months follow-up assessment (CT: n = 25, PT: n = 24). Primary study outcomes were memory and executive functioning composite scores. Mixed repeated measures ANOVAs, post-hoc t tests and multiple regression analyses were conducted. Results We found a significant time x group interaction effect for the memory composite score (p = 0.006, η2 = 0.214), but not for the executive composite score (p = 0.967, η2 = 0.002). Post-hoc t tests revealed significant verbal and nonverbal memory improvements from pre-intervention to 6 months, but not to 12 months follow-up assessment in the CT group. No significant predictors were found for predicting memory improvement after CT. Conclusions This study provides Class 1 evidence that multidomain CT enhances memory functioning in PD-MCI after 6 months but not after 12 months, whereas executive functioning did not change in the long-term. Clinical trial registration German Clinical Trials Register (ID: DRKS00010186), 21.3.2016 (The study registration is outlined as retrospective due to an administrative delay. The first patient was enrolled three months after the registration process was started. A formal confirmation of this process from the German Clinical Trials Register can be obtained from the authors.)

Alzheimer's & dementia 13(1), e12223 (2021). doi:10.1002/dad2.12223, Published by Wiley, Hoboken, NJ

Background: Assessment of affective-behavioral states in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS) is essential. Objective: To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. Methods: Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach’s alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. Results: The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach’s alpha = 0.72–0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84–0.95). Sensitivities and specificities exceeded 0.7. Conclusion: The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted.

We investigated whether Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) influences social validation as measured by a Judge-Advisor task. In contrast to healthy controls and patients with their DBS OFF, patients with their stimulation switched on do not experience a gain of confidence after receiving competent advice.

Background: Music-assisted treadmill training (MATT) is a new therapeutic approach for Parkinson's disease (PD) patients, combining treadmill training with rhythmic auditory cueing and visual feedback. PD studies have shown larger positive effects on motor outcomes than usual treadmill training. However, effects on cognition, in contrast, are less clear. Existing studies provided intensive training protocols and included only stable medicated patients. Thus, a pilot randomized controlled trial was designed to analyze the feasibility of a shorter training protocol as well as preliminary effects on cognition, motor function, and patient-centered outcomes in a rehabilitation setting where PD patients with and without deep brain stimulation (DBS) undergo adaptation of medication and DBS settings. Here, we present the results from the feasibility analysis of the still ongoing trial. Methods: Non-demented PD patients with and without DBS were recruited during their inpatient rehabilitation and randomized to an experimental group (EG; 20 min MATT) or an active control group (CG; 20 min bike ergometer training). The trainings took place for 8 consecutive days and were added to the usual rehabilitation. Feasibility was assessed with the following parameters: patients' study protocol acceptance, study protocol transferability into clinical routine, training-induced adverse events, and patients' training perception. Results: Thirty-two patients (EG: n = 15; CG: n = 17; 72% DBS) were included. The study protocol was well-accepted (inclusion rate: 84%). It was transferable into clinical routines; dropout rates of 40% (EG) and 18% (CG) were observed. However, an in-depth analysis of the dropout cohort did not reveal intervention-related dropout reasons. The MATT and the standard ergometer training showed no adverse events and were positively perceived by PD patients with and without DBS. Conclusion: MATT was shown to be a feasible, safe, and enjoyable treatment option in PD patients with and without DBS. Furthermore, the dropout cohort analysis revealed some exciting first insights into possible dropout reasons that go beyond the form of intervention. Therefore, research would benefit from a common practice of dropout analyses, as this would enhance our understanding of patients' therapy adherence and expectations.

Today, meta-analyses demonstrate that cognitive training is safe and effective to enhance vulnerable cognitive functions in patients with Parkinson’s disease (PD), so that cognitive interventions can be regarded as a promising approach to treat or even prevent cognitive dysfunction in PD. However, many research gaps exist. Thus, this article aims to identify relevant research topics with regard to cognitive interventions in PD patients for the next 20 years. The most important to do's include the development of (non-digital and digital, maybe also artificial intelligence based) standardized cognitive interventions for PD patients in different cognitive stages and the conduct of large randomized controlled trials (RCTs) in these groups, also considering different patient profiles (e.g., motor subtypes) and the living setting (inpatient versus outpatient). The impact of cognitive and combined interventions in individuals with prodromal PD is of high relevance. Studies should elucidate underlying mechanisms of cognitive and neural plasticity induced by cognitive interventions and propose prediction models on which patients profit from which intervention. Health-economic analyses are also urgently needed. More generally, increasing the awareness of the concept of cognitive reserve and possibilities for the prevention of cognitive dysfunction is an important goal.

Fur eine umfassende Beschreibung und Quantifizierung neuropsychologischer Defizite bedarf es einer ausgedehnten neuropsychologischen Diagnostik, deren Zeitaufwand sich nicht jedes Setting leisten kann und auch nicht immer notwendig ist. Anfangs bieten sich Screeningverfahren an. Da sich deren Auswahl zwischen und manchmal sogar innerhalb von Kliniken unterscheidet, ware es hilfreich, Ergebnisse in verschiedenen Verfahren miteinander vergleichen zu konnen. Die gegenwartige Studie setzt sich dies fur den deutschsprachigen Raum zum Ziel, d. h. Konversionen zwischen den Summenscores des Mini-Mental-Status-Tests (MMST), des Montreal Cognitive Assessments (MoCA) und des Demenzdetektionstests (DemTect) sollen vorgenommen werden konnen. In den Jahren 2008 bis 2017 wurden insgesamt 8240 Patienten der Klinik und Poliklinik fur Neurologie in der Uniklinik Koln mit verschiedenen neurologischen Erkrankungen untersucht. Mithilfe der Methode des Equipercentil-Equatings wurden die Ergebnisse im MMST, MoCA und DemTect untereinander konvertiert. Die berechneten bidirektionalen Konversionstabellen ermoglichen einen schnellen und einfachen Vergleich der drei am haufigsten verwendeten Screenings. Zudem gleichen sie ungefahr denen vergangener Studien aus dem englischen Sprachraum. Die Ergebnisse ermoglichen eine verbesserte longitudinale Erfassung kognitiver Funktionen bei verschiedenen klinischen Settings, gewahren eine Vergleichbarkeit und bieten erhohte Flexibilitat bei der Statusbestimmung von Patienten an. Eine Erweiterung dieser Studie ware die Ubertragung der vorgestellten Methode auf andere kognitive bzw. affektive Domanen, wie z. B. Gedachtnis oder Depression.

Introduction The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA. Methods In 202 non-demented PD patients, we evaluated cognitive status, clinical and demographic data, as well as the MoCA with a weighted and unweighted score. Receiver operating characteristic (ROC) curve analysis was used to evaluate discriminative ability of the MoCA. Group comparisons and ROC analysis were performed for PD-MCI classifications with a cut-off

Although other nonmotor phenomena representing possible prodromal symptoms of Parkinson's disease have been described in some detail, the occurrence and characteristics of cognitive decline in this early phase of the disease are less well understood. The aim of this review is to summarize the current state of research on cognitive changes in prodromal PD. Only a small number of longitudinal studies have been conducted that examined cognitive function in individuals with a subsequent PD diagnosis. However, when we consider data from at-risk groups, the evidence suggests that cognitive decline may occur in a substantial number of individuals who have the potential for developing PD. In terms of specific cognitive domains, executive function in particular and, less frequently, memory scores are reduced. Prospective longitudinal studies are thus needed to clarify whether cognitive, and specifically executive, decline might be added to the prodromal nonmotor symptom complex that may precede motor manifestations of PD by years and may help to update the risk scores used for early identification of PD. © 2017 International Parkinson and Movement Disorder Society.

Nichtmedikamentose Therapien zur Behandlung der Parkinson-Erkrankung beinhalten Physio-, Ergotherapie, Logopadie, kognitive Trainingsverfahren sowie die tiefe Hirnstimulation und nichtinvasive Hirnstimulationsverfahren. Mit der Diagnose der Parkinson-Krankheit konnen aktivierende Therapien, wie die Bewegungstherapien und die Logopadie – angepasst an das Symptomprofil des Patienten, – hilfreich sein. Milde kognitive Beeintrachtigungen sind haufig im Verlauf der Parkinson-Erkrankung messbar und ein Progress dieser Storungen bis hin zu einer demenziellen Entwicklung im fortgeschrittenen Krankheitsstadium ist nicht selten. Wann ein kognitives Training empfohlen werden kann und mit welcher Trainingsmethodik und Haufigkeit dieses angewendet werden sollte, ist Gegenstand aktueller Forschung. Die tiefe Hirnstimulation ist ein etabliertes Verfahren, welches dann in Erwagung gezogen werden sollte, wenn hinderliche motorische Fluktuationen durch medikamentose Therapiemoglichkeiten nicht ausreichend behandelt werden konnen. Diese Therapieform ist zudem an spezifische patientenorientierte Bedingungen geknupft und bedarf der Abstimmung in einem multiprofessionellen Team. Nichtinvasive Stimulationstechniken beinhalten die repetitive transkranielle Magnetstimulation und die transkranielle Gleichstromstimulation, welche experimentelle Therapiemodalitaten darstellen und auserhalb von Studienprotokollen derzeit nicht empfohlen werden konnen.

Background. Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson’s disease (PD) patients. However, the patients’ cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted. Objective. To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictors. Methods. Sixty-four PD-MCI patients (age: 67.61 ± 7.70; UPDRS-III: 26.58 ± 13.54; MoCA: 24.47 ± 2.78) were randomized to either a CT group or a low-intensity physical activity CG for six weeks (twice weekly, 90 minutes). Outcomes were assessed before and after training. MANOVAs with follow-up ANOVAs and multiple regression analyses were computed. Results. Both interventions were highly feasible (participation, motivation, and evaluation); the overall dropout rate was 4.7%. Time × group interaction effects favoring CT were observed for phonemic fluency as a specific executive test ( p = 0.018 , η p 2 = 0.092 ) and a statistical trend for overall executive functions ( p = 0.095 , η p 2 = 0.132 ). A statistical trend for a time × group interaction effect favoring CG was shown for the digit span backward as a working memory test ( p = 0.098 , η p 2 = 0.043 ). Regression analyses revealed cognitive baseline levels, education, levodopa equivalent daily dose, motor scores, and ApoE status as significant predictors for CT success. Conclusions. CT is a safe and feasible therapy option in PD-MCI, yielding executive functions improvement. Data indicate that vulnerable individuals may show the largest cognitive gains. Longitudinal studies are required to determine whether CT may also attenuate cognitive decline in the long term. This trial is registered with DRKS00010186.

Objective To determine the feasibility and evaluate effects of a computerized working memory (WM) training (WMT) in patients with Parkinson's Disease (PD) on cognitive and clinical outcomes. Methods 76 patients with PD without cognitive impairment were randomized to either the WMT group (n = 37), who participated in a 5-week adaptive WMT, or a passive waiting-list control group (CG, n = 39). Patients underwent clinical and neuropsychological examination at baseline, after training, and at 3-months follow-up, with verbal WM and non-verbal WM as primary outcomes. Outcome assessors were blinded for group allocation. Results All WMT participants completed the training successfully and reported high levels of motivation for and satisfaction with the training. Repeated-measures, linear mixed-effects models revealed positive training effects for the WMT group compared to the CG in verbal working memory with a small relative effect size 0.39 [95%CI 0.05; 0.76] for the 3-months follow-up only. No other reliable training effects in cognitive and clinical variables were found for either point of time. Conclusions In this randomized controlled trial, WMT was feasible and yielded some evidence for 3-months follow-up training gains in patients with PD. WMT might be an effective intervention to prevent cognitive decline in this patient group, however, more longitudinal studies with longer follow-up periods and more sensitive assessment tools will have to proof this concept. Trial registration German Clinical Trials Register (DRKS00009379).

Introduction: The Aphasia Check List (ACL) is a comprehensive, time-saving tool for language evaluation in aphasia, including a cognitive assessment part. This cross-sectional study aimed to translate ACL into Persian and analyze the psychometric features of the translated version. The original version of the ACL was translated and adapted from German; its psychometric features were then determined. Methods: Twenty People With Aphasia (PWA) and 50 age- and education-matched, cognitively healthy controls participated in this research. Possible floor and ceiling effects, discriminant validity, test-retest reliability, and internal consistency of the test were analyzed in addition to the evaluation of internal correlations between the test parts (language & cognition). Results: Regarding the performance of PWAs in the language section and the cognitive subtests assessing attention, memory, and reasoning, there were no floor and ceiling effects. Adequate discriminant validities for the language section of the test [i.e., total score: (Mann-Whitney U= 6.000, P

Background IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment. Methods NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics. Results The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients. Conclusion It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own. Electronic supplementary material The online version of this article (10.1186/s40035-019-0153-0) contains supplementary material, which is available to authorized users.

Background While the efficacy of cognitive stimulation (CS) has been demonstrated in patients with dementia, no study has included patients with Parkinson's disease dementia (PDD). Objective For the first time, this randomized crossover pilot study examined the feasibility and potential effects of CS in PDD. Methods All residents of a PDD-specific long-term care unit in the Netherlands that were eligible for the study (n=12) were randomly allocated to group A (n=6) receiving CS (eight weeks, twice weekly for 60 minutes) or group B (n=6) receiving usual care (control group, CG). The CG participated in CS afterwards, resulting in an experimental group (EG), consisting of n=12. Pre- and postassessments and a six-week follow-up (FU) were conducted for cognition, neuropsychiatric symptoms, quality of life (QoL), and activities of daily living (ADL) outcomes. Results Between-group analysis with difference scores from pre- to posttest revealed a group difference for global cognition (CERAD total score) favoring the EG, with a moderate effect size and a p value just failing to reach statistical significance (p=0.067; r = 0.43). A further statistical trend was observed for neuropsychiatric symptoms, again with a moderate effect size (p=0.075; r = 0.42). Within-group analyses indicated improvement only in the EG with large effects also just failing to reach significance for global cognition (short term, p=0.060; r = 0.70) as well as for depression (long term, p=0.072; r = 0.61). ADL deteriorated significantly at FU in the EG (p=0.014; r = 0.71). Conclusions Although our data are preliminary due to the small sample size, this study shows that CS is feasible and potentially effective for cognitive and noncognitive outcomes in PDD patients. Randomized controlled trials with larger sample sizes are needed to confirm these promising results.

Das Kolner Apraxie-Screening (KAS) erfasst apraktische Defizite nach linkshemispharischen Schlaganfallen. Ziel dieser Studie ist es, durch Anpassungen des Testmaterials des KAS und psychometrische Analysen ein diagnostisches Verfahren fur Patienten mit rechtshemispharischem Schlaganfall zu entwickeln. Mittels Itemanalysen von Daten 77 gesunder Probanden und 100 rechtshemispharischer Schlaganfallpatienten wurden 8 KAS-Items ausgeschlossen. Das somit noch aus 12 Items bestehende KAS-R weist eine gute interne Konsistenz (α = 0,795) sowie eine hohe Sensitivitat (79,4 %) und Spezifitat (84,4 %) auf. Bei einem Cut-off-Wert von ≤ 46 (von 48) Punkten zeigen 39 der 100 Schlaganfallpatienten eine Apraxie. Dabei korreliert das KAS-R – im Sinne einer guten Konstruktvaliditat – signifikant mit den externen Validierungsverfahren. Die Ergebnisse zeigen, dass das KAS-R ein reliables und valides diagnostisches Verfahren fur apraktische Defizite nach rechtshemispharischem Schlaganfall ist.

Introduction Cognitive impairment is a common and disabling non-motor symptom in Parkinson's disease (PD). The apolipoprotein E (APOE) allele e4 is a known risk factor for Alzheimer's disease and has also been suggested to be a risk factor for dementia in PD and even a predictor of impairment in certain cognitive domains. Methods A total of 447 PD patients (PD patients without cognitive impairment: n = 187; PD patients with mild cognitive impairment: n = 188; PD patients with dementia: n = 72) were included from an ongoing observational German multicenter cohort study (LANDSCAPE study). All patients underwent an extensive neuropsychological test battery, including assessments of memory, visuospatial functioning, attention, language, and executive function. APOE genotype was determined by an allelic discrimination assay. Linear regression analysis was used to explore the associations between APOE-e4 and cognitive performance. Results The APOE-e4 allele was not associated with a diagnosis of cognitive impairment in PD (PD with mild cognitive impairment and PD with dementia) or with deficits in specific neuropsychological domains in our study cohort. Conclusion Our data question the relevance of the APOE-e4 allele as a predictor of cognitive impairment in PD.

Background Cognitive impairment (CI) is frequently observed in Parkinson's disease (PD) and negatively influences the patient's and carer's quality of life. As a first step, assessment of CI is often accomplished by using screening instruments (level I diagnosis). Three commonly used instruments are the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Parkinson Neuropsychometric Dementia Assessment (PANDA). Because different preferences regarding test selection exist between clinics, this study aims to provide evidence about the concordance of these tests. It also converts total test scores of the three instruments to assist clinical practice. Methods Between January and December 2018, 96 patients with idiopathic PD were examined at the University Hospital of Cologne, Germany. Comparability of MMSE, MoCA, and PANDA scores was investigated by calculating correlations, classification agreements, and percentile ranks. Additionally, we converted test scores among the three screening instruments by implementing the equipercentile equating method and log-linear smoothing. Results The MMSE classified 26%, the PANDA 32.3% and the MoCA 54.2% of PD patients as having CI. The screening instruments' concordance in classifying cognition into normal cognition versus CI was 75% (AC1 = 0.62) for MMSE and PANDA, 63.5% (AC1 = 0.28) for MoCA and PANDA, and 57.3% (AC1 = 0.24) for MMSE and MoCA. The provided conversion table enables a quick and easy transformation of the three screening instruments within PD diagnostics. Conclusion These results contribute to a better understanding of the screenings' utility and concordance in a population of PD patients. Additionally, communication between clinics may be enhanced.

We investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1-weighted longitudinal 3T MRI data (up to four follow-up assessments) from neuropsychologically well-characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas-based volumetry and cortical thickness measures. At baseline, PD patients presented with cerebral atrophy and cortical thinning including striatum, temporoparietal regions, and primary/premotor cortex. The atrophy was already observed in “cognitively normal” PD patients (PD-N) and was considerably more pronounced in cognitively impaired PD patients. Linear mixed effect modeling revealed almost similar rates of atrophy change in PD and controls. The group comparison at baseline between those PD-N whose cognitive performance remained stable (n = 42) and those PD-N patients who converted to MCI/PDD (“converter” cPD-N, n = 26) indicated suggested cortical thinning in the anterior cingulate cortex in cPD-N patients which was correlated with cognitive performance. Our results suggest that cortical brain atrophy has been already expanded in advanced PD patients without overt cognitive deficits while atrophy progression in late disease did not differ from “normal” aging regardless of the cognitive status. It appears that cortical atrophy begins early and progresses already in the initial disease stages emphasizing the need for therapeutic interventions already at disease onset. CA extern

ObjectivesParkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.MethodsDemographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.ResultsCompared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).ConclusionThe three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Background: Cognitive dysfunction is one of the most prevalent non-motor symptoms in Parkinson’s disease (PD), often experienced as more debilitating for patients and caregivers than motor problems. Therefore, a deeper understanding of the course of cognitive decline and the identification of valid progression markers for Parkinson’s disease dementia (PDD) is essential. Objective: This systematic review summarizes the current state of knowledge on cognitive decline over time by reporting effect sizes of cognitive changes in neuropsychological tests. METHODS: 1368 studies were identified by a PubMed database search and 25 studies by additionally scanning previous literature. After screening all records, including 69 full-text article reviews, 12 longitudinal studies on the progression of cognitive decline in PD met our criteria (e.g., sample size ≥50 patients). Results: Only a few studies monitored cognitive decline over a longer period (>4 years). Most studies focused on the evaluation of change in global cognitive state by use of the Mini-Mental State Examination, whereas the use of neuropsychological tests was highly heterogenic among studies. Only one study evaluated patients’ cognitive performance in all specified domains (executive function, attention & working memory, memory, language, and visual-spatial function) allowing for diagnosis of cognitive impairment according to consensus guidelines. Medium to strong effect sizes could only be observed in studies with follow-up intervals of four years or longer. Conclusions: The results emphasize the need for the assessment of larger PD cohorts over longer periods of follow-up with a comprehensive neuropsychological battery.

Objective: Patients with Parkinson’s disease (PD) can show impaired self-awareness of motor deficits (ISAm). We developed a new scale that measures ISAm severity of hyper- and hypokinetic movements in PD during medication on state and defined its psychometric criteria. Method: Included were 104 right-handed, non-depressed, non-demented patients. Concerning ISAm, 38 motor symptoms were assessed using seven tasks, which were performed and self-rated concerning presence of deficit (yes/no) by all patients. The whole procedure was videotaped. Motor symptoms were then evaluated by two independent experts, blinded for patient’s ratings, concerning presence, awareness of deficit, and severity. Exploratory principal component analysis (promax rotation) was applied to reduce items. Principal axis factoring was conducted to extract factors. Reliability was examined regarding internal consistency, split-half reliability, and interrater reliability. Validity was verified by applying two additional measures of ISAm. Results: Of the initial 38 symptoms, 15 remained, assessed in five motor tasks and merged to a total severity score. Factor analysis resulted in a four factor solution (dyskinesia, resting tremor right hand, resting tremor left hand, bradykinesia). For all subscales and the total score, measures of reliability (values 0.64–0.89) and validity (effect sizes>0.3) were satisfactory. Descriptive results showed that 66% of patients had signs of ISAm (median 2, range 0–15), with ISAm being most distinct for dyskinesia. Conclusions: We provide the first validation of a test for ISAm in PD. Using this instrument, future studies can further analyze the pathophysiology of ISAm, the psychosocial sequelae, therapeutic strategies and compliance with therapy. (JINS, 2015, 21, 1–10)

The most frequently used instrument to assess health-related quality of life (HrQoL) in Parkinson’s disease (PD) is the Parkinson’s Disease Questionnaire 39 (PDQ-39). However, both the dimensionality of the eight PDQ-39 subscales and their summary score recently faced criticism. Furthermore, data on disease-related and neuropsychological determinants and the role of gender on HrQoL in PD are inconclusive yet. Therefore, our aim was to reevaluate the PDQ-39 structure and to further explore determinants of HrQoL in PD. 245 PD patients (age: M = 69.64, SD = 8.43; 62.9% male; H&Y: Md = 3.00; cognitive assessment with PANDA: M = 24.82, SD = 3.57) from the baseline database of the Cologne Parkinson Network were used to reevaluate the dimensionality of the PDQ-39 with a principal component analysis (PCA). Multiple regression analyses were conducted to clarify general and domain-specific relationships between clinical, (neuro)psychological, and sociodemographic variables, gender in particular, and HrQoL. The PCA identified three HrQoL domains: physical-functioning, cognition, and socioemotional HrQoL. Depressive symptoms were identified as the most important determinant of HrQoL across all models. Disease-related HrQoL determinants (UPDRS-III, H&Y stage, and LEDD) were less strong and consistent HrQoL determinants than nonmotor symptoms. Analyses did not reveal a global gender effect; however, female gender was a negative predictor for physical-functioning and socioemotional HrQoL, whereas male gender was a negative predictor for cognition HrQoL. Our analyses suggest the consideration of a reevaluation of the PDQ-39. Only the full understanding of HrQoL, its determinants, and their interrelationships will allow the development of PD intervention strategies focusing on what matters the most for patients’ HrQoL. Gender is one relevant variable that should be considered in this context.

Background. While the efficacy of cognitive stimulation (CS) has been demonstrated in patients with dementia, no study has included patients with Parkinson’s disease dementia (PDD). Objective. For the first time, this randomized crossover pilot study examined the feasibility and potential effects of CS in PDD. Methods. All residents of a PDD-specific long-term care unit in the Netherlands that were eligible for the study (n=12) were randomly allocated to group A (n=6) receiving CS (eight weeks, twice weekly for 60 minutes) or group B (n=6) receiving usual care (control group, CG). The CG participated in CS afterwards, resulting in an experimental group (EG), consisting of n=12. Pre- and postassessments and a six-week follow-up (FU) were conducted for cognition, neuropsychiatric symptoms, quality of life (QoL), and activities of daily living (ADL) outcomes. Results. Between-group analysis with difference scores from pre- to posttest revealed a group difference for global cognition (CERAD total score) favoring the EG, with a moderate effect size and a p value just failing to reach statistical significance (p=0.067; r = 0.43). A further statistical trend was observed for neuropsychiatric symptoms, again with a moderate effect size (p=0.075; r = 0.42). Within-group analyses indicated improvement only in the EG with large effects also just failing to reach significance for global cognition (short term, p=0.060; r = 0.70) as well as for depression (long term, p=0.072; r = 0.61). ADL deteriorated significantly at FU in the EG (p=0.014; r = 0.71). Conclusions. Although our data are preliminary due to the small sample size, this study shows that CS is feasible and potentially effective for cognitive and noncognitive outcomes in PDD patients. Randomized controlled trials with larger sample sizes are needed to confirm these promising results.

Positive Effekte kognitiver und physischer Trainings auf die Kognition gesunder alterer Menschen sind gut belegt. Zunehmend wird diskutiert, ob durch deren Kombination starkere Effekte erreicht werden konnen. In dieser Arbeit wird der Forschungsstand dazu aufgearbeitet. Vier randomisierte kontrollierte Studien (RCTs) und vier kontrollierte Studien wurden gefunden. In drei Studien, jedoch keiner RCT, wurde tatsachlich eine Uberlegenheit von kombiniertem Training im Vergleich zu Einzelinterventionen in Bezug auf die Kognition gefunden. Wenngleich also positive Hinweise vorliegen, ist der Forschungsstand aufgrund der insgesamt geringen Studienzahl, des Mangels an Evidenz aus RCTs und der mangelnden Vergleichbarkeit der Studien hinsichtlich der Studiendesigns, der Art der Intervention und der Messzeitpunkte als unzureichend zu bewerten. Forschungslucken werden aufgezeigt, wesentliche Aspekte fur zukunftige Studien genannt und mogliche neurobiologische Mechanismen von Trainingseffekten diskutiert.

Bei seiner Entwicklung zeigte sich bereits, dass die Ergebnisse des DemTect, eines im deutschsprachigen Raum haufig genutzten kognitiven Screeningverfahrens, alters-, aber nicht bildungsabhangig sind. Bislang standen deshalb Auswertungsroutinen fur Uber- und Unter-60-Jahrige zur Verfugung. Um den Alterseffekt umfassender beschreiben zu konnen, wurde der DemTect nun bei Unter-40-Jahrigen (n = 105; Altersmedian 33 Jahre [18 – 39]) und Uber-80-Jahrigen (n = 68; Altersmedian 83 Jahre [80 – 93]) durchgefuhrt und entsprechende Auswertungsroutinen wurden erstellt. Nach einer Transformierung der Rohwerte, die sich wie gehabt an den Mittelwerten und Standardabweichungen der jeweiligen Referenzgruppe orientiert, konnte eine Punktezuordnung vorgenommen werden, nach der die Gruppen im transformierten Gesamtwert sowie den transformierten Subtestwerten nicht mehr statistisch unterscheidbar sind. Der Median des transformierten Gesamtwerts liegt bei 16 5 6 7 8 9 10 11 12 13 14 15 16 17 18 fur die jungeren und bei 15 5 6 7 8 9 10 11 12 13 14 15 16 17 18 fur die alteren Probanden. Die neue Punktevergabe stellt eine Erganzung zu den DemTect-Auswertungsmoglichkeiten fur die Gruppen der Unter-40- und der Uber-80-Jahrigen dar.

Background In Parkinson's Disease (PD), cognitive dysfunctions which can reduce patients' quality of life occur frequently. Data on non-pharmacological intervention effects on cognitive functions in patients with PD are rare. The aim of this study was to examine the effects of different cognitive group trainings (structured vs. unstructured) on cognition, depression, and quality of life in non-demented PD patients. Methods In this randomized controlled trial, 65 non-demented patients with PD according to UK Brain Bank criteria (Hoehn & Yahr I-III) were allocated to one of two cognitive multi-component treatments (“NEUROvitalis”, a structured training, or the unstructured training “Mentally fit” with randomly assembled cognitive tasks, each including 12 group-sessions a 90 min over 6 weeks) or a waiting list control group (CG). A neuropsychological test battery was performed before and after the training. Results Compared to the CG, patients from the “NEUROvitalis” group improved in short-term memory (word list learning “Memo”: p p p p Discussion Cognitive and affective functions can be improved by cognitive trainings in PD patients. Specific effects (e.g. on memory and working memory versus depression) seem to be dependent on the type of training. Further research is needed to define long-term effects and the efficacy in PD patients with different extent of cognitive and neuropsychiatric symptoms.

Objectives To investigate hypomania and mania related to dopamine replacement therapy (DRT) in Parkinson's disease (PD). Methods We recruited 108 non-demented PD patients without deep brain stimulation from a movement disorders in and outpatient clinic. Forty-five age- and gender-matched controls were also included. Disease characteristics, cognitive functioning, comorbid psychiatric diseases, dopaminergic and psychiatric medication were evaluated. Diagnosis of DRT-related hypomania and mania was based on DSM-IV-TR criteria with supplementary assessment of two mania self-rating scales. First, patients and controls were compared. Patients with DRT-related hypomania or mania were then compared to the remaining patients. A binary logistic regression analysis was performed to identify correlates of DRT-related hypomania. Results Patients scored significantly higher on mania self-rating scales than controls. Twelve patients (11.1%) had DRT-related hypomania and six patients (5.6%) had DRT-related mania. Both groups had significantly higher self-rating mania-scores than patients without these mood states. DRT-related hypomania was significantly related to younger age, younger age at PD onset, dyskinesias, higher levodopa equivalent daily dose, dopamine dysregulation, and amantadine treatment. In contrast, DRT-related mania was significantly associated with hallucinations and delusions, history of levodopa-induced psychosis, quetiapine treatment, higher depression and daily levodopa dose, and cognitive deficits. Regression analysis revealed dopamine dysregulation, dyskinesias, amantadine treatment, and younger age at PD onset as significant correlates of DRT-related hypomania. Conclusion DRT-related hypomania and mania are relevant comorbidities in PD. DRT-related hypomania may exist as a distinct psychiatric symptom complex in young patients with early disease onset. Different patient profiles likely underlie DRT-related hypomania and mania.

While visuo-spatial deficits are well characterized cognitive sequelae of right hemisphere (RH) stroke, apraxic deficits in RH stroke remain poorly understood. Likewise, very little is known about the association between apraxic and visuo-spatial deficits in RH stroke or about the putative common or differential pathophysiology underlying these deficits. Therefore, we examined the behavioral and lesion patterns of apraxic deficits (pantomime of object use and bucco-facial imitation) and visuo-spatial deficits (line bisection and letter cancellation tasks) in 50 sub-acute RH stroke patients. Using principal component analysis (PCA), we characterized the relationship between the two deficits. We hypothesized that any interaction of these neuropsychological measures may be influenced by the demands of ego-centric/space-based and/or allo-centric/object-based processing. Contra-lesional visuo-spatial deficits were common in our clinically representative patient sample, affecting more than half of RH stroke patients. Furthermore, about one third of all patients demonstrated apraxic deficits. PCA revealed that pantomiming and the imitation of bucco-facial gestures loaded clearly on a first component (PCA1), while letter cancellation loaded heavily on a second component (PCA2). For line bisection, overall mean deviation loaded on PCA1, while the difference between the mean deviations in contra- versus ipsi-lesional space loaded on PCA2. These results propose that PCA1 represents allo-centric/object-based processing and PCA2 2 ego-centric/space-based processing. This interpretation was corroborated by the statistical lesion analyses with the component scores. Data suggest that apraxic pantomime and imitation deficits in RH stroke result, at least in part, from disturbed allo-centric/object-based processing.

Schlaganfall-induzierte neuropsychologische Einschrankungen stellen haufige und fur die Prognose relevante Symptome dar, sodass ihre Diagnostik zum fruhestmoglichen Zeitpunkt indiziert ist. Da Schlaganfall-Patienten in der Akut- und Subakutphase eines Schlaganfalls oft verlangsamt und vermindert belastbar sind, ist eine neuropsychologische Untersuchung haufig nur eingeschrankt und mit Instrumenten moglich, die an der Bettkante durchfuhrbar und moglichst fur diese Patientengruppe normiert sind. Hier wird ein Uberblick uber aktuell im deutschsprachigen Raum verfugbare neuropsychologische, diagnostische Instrumente gegeben, die fur Schlaganfall-Patienten in fruhen Schlaganfall- und Rehabilitations-Phasen entwickelt wurden oder bei diesen angewendet werden. Eines der neun hier vorgestellten Verfahren ist das neu entwickelte Kolner Neuropsychologische Screening fur Schlaganfall-Patienten, das kurz vorgestellt wird. Die Verfahren unterscheiden sich deutlich in Form der Untersuchung, Bearbeitungsdauer, Materialaufwand und Normierung. Die Wahl des Verfahrens im klinischen und wissenschaftlichen Kontext hangt masgeblich von der aktuellen Fragestellung sowie der Belastbarkeit des Patienten ab.