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Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P <.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR =.77) than chronic patients (Mdn =.15/IQR = 1.68/P =.015). There was no significant rTMS effect in the chronic aphasia group. Conclusions: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration: https://clinicaltrials.gov/ct2/show/NCT02020421.

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 verbalWMwith 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.

Introduction Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare. Methods Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. Results Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI. Discussion The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.

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

Background. Patients with Parkinson's disease (PD) are highly vulnerable to develop cognitive dysfunctions, and the mitigating potential of early cognitive training (CT) is increasingly recognized. Predictors of CT responsiveness, which could help to tailor interventions individually, have rarely been studied in PD. This study aimed to examine individual characteristics of patients with PD associated with responsiveness to targeted working memory training (WMT). Methods. Data of 75 patients with PD (age: 63.99 +/- 9.74 years, 93% Hoehn & Yahr stage 2) without cognitive dysfunctions from a randomized controlled trial were analyzed using structural equation modeling. Latent change score models with and without covariates were estimated and compared between the WMT group (n = 37), who participated in a 5-week adaptive WMT, and a waiting list control group (n = 38). Results. Latent change score models yielded adequate model fit (chi(2)-test p > .05, SRMR <= .08, CFI >= .95). For the near-transfer working memory composite, lower baseline performance, younger age, higher education, and higher fluid intelligence were found to significantly predict higher latent change scores in the WMT group, but not in the control group. For the far-transfer executive function composite, higher self-efficacy expectancy tended to significantly predict larger latent change scores. Conclusions. The identified associations between individual characteristics and WMT responsiveness indicate that there has to be room for improvement (e.g., lower baseline performance) and also sufficient hardware (e.g., younger age, higher intelligence) to benefit in training-related cognitive plasticity. Our findings are discussed within the compensation versus magnification account. They need to be replicated by methodological high-quality research applying advanced statistical methods with larger samples.

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 R-2 = 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.

Even after a long time of research on dual-tasking, the question whether the two tasks are always processed serially (response selection bottleneck models, RSB) or also in parallel (capacity-sharing models) is still going on. The first models postulate that the central processing stages of two tasks cannot overlap, producing a central processing bottleneck in Task 2. The second class of models posits that cognitive resources are shared between the central processing stages of two tasks, allowing for parallel processing. In a series of three experiments, we aimed at inducing parallel vs. serial processing by manipulating the relative frequency of short vs. long SOAs (Experiments 1 and 2) and including no-go trials in Task 2 (Experiment 3). Beyond the conventional response time (RT) analyses, we employed drift–diffusion model analyses to differentiate between parallel and serial processing. Even though our findings were rather consistent across the three experiments, they neither support unambiguously the assumptions derived from the RSB model nor those derived from capacity-sharing models. SOA frequency might lead to an adaptation to frequent time patterns. Overall, our diffusion model results and mean RTs seem to be better explained by participant’s time expectancies.

Background: Cognitive impairment is a very frequent and severe nonmotor symptom of Parkinson's disease (PD). Early intervention in this at-risk group for cognitive decline may be crucial for long-term preservation of cognitive functions. Computerized working memory training (WMT) has been proven beneficial in non-PD patient populations, but such evidence is still needed for patients with PD. Objective: This study aimed to evaluate the effect of WMT on visuo-spatial working memory (WM) in cognitively unimpaired patients with PD. Methods: A single-blind randomized controlled trial encompassing 76 patients with PD but no cognitive impairment according to level II diagnostic criteria was conducted. Thirty-seven patients engaged in home-based adaptive WMT 5 times per week for a period of 5 weeks, whereas the remaining patients were in the waiting list arm of the study (control group [CG]). Working memory performance was evaluated using a computerized task before and after intervention and at 14-week follow-up, allowing to quantify the precision of WM on a continuous scale, ie, to test not only if an item was remembered but also how well the location of this item was retained. Results: Coincidently, the WMT group showed slightly worse WM performance compared with the CG at baseline, which was ameliorated after WMT. This training-induced effect remained stable until follow-up. Conclusion: Patients showing relatively low WM performance, despite not formally diagnosable as Parkinson's disease with mild cognitive impairment (PD-MCI), seem to benefit from home-based WMT. Thus, WMT could potentially be implemented in future trials as a time- and cost-efficient route to counteract subtle cognitive changes in early disease stages.

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

Background: Research on predictors of working memory training responsiveness, which could help tailor cognitive interventions individually, is a timely topic in healthy aging. However, the findings are highly heterogeneous, reporting partly conflicting results following a broad spectrum of methodological approaches to answer the question who benefits most from working memory training. Objective: The present systematic review aimed to systematically investigate prognostic factors and models for working memory training responsiveness in healthy older adults. Method: Four online databases were searched up to October 2019 (MEDLINE Ovid, Web of Science, CENTRAL, and PsycINFO). The inclusion criteria for full texts were publication in a peer-reviewed journal in English/German, inclusion of healthy older individuals aged >= 55 years without any neurological and/or psychiatric diseases including cognitive impairment, and the investigation of prognostic factors and/or models for training responsiveness after targeted working memory training in terms of direct training effects, near-transfer effects to verbal and visuospatial working memory as well as far-transfer effects to other cognitive domains and behavioral variables. The study design was not limited to randomized controlled trials. Results: A total of 16 studies including n = 675 healthy older individuals with a mean age of 63.0-86.8 years were included in this review. Within these studies, five prognostic model approaches and 18 factor finding approaches were reported. Risk of bias was assessed using the Quality in Prognosis Studies checklist, indicating that important information, especially regarding the domains study attrition, study confounding, and statistical analysis and reporting, was lacking throughout many of the investigated studies. Age, education, intelligence, and baseline performance in working memory or other cognitive domains were frequently investigated predictors across studies. Conclusions: Given t

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 x group interaction effects favoring CT were observed for phonemic fluency as a specific executive test (p=0.018, eta(2)(p)=0.092) and a statistical trend for overall executive functions (p=0.095, eta(2)(p)=0.132). A statistical trend for a time x group interaction effect favoring CG was shown for the digit span backward as a working memory test (p=0.098, eta(2)(p)=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.

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' I IrQoL. Gender is one relevant variable that should be considered in this context.