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 the methodological shortcomings of the included studies, no clear conclusions can be drawn, and emerging patterns of prognostic effects will have to survive sound methodological replication in future attempts to promote precision medicine approaches in the context of working memory training. Methodological considerations are discussed, and our findings are embedded to the cognitive aging literature, considering, for example, the cognitive reserve framework and the compensation vs. magnification account. The need for personalized cognitive prevention and intervention methods to counteract cognitive decline in the aging population is high and the potential enormous. Registration: PROSPERO, ID CRD42019142750.

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: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) cohorts have provided insights into the earliest neurodegenerative processes in α‐synucleinopathies. Even though polysomnography (PSG) remains the gold standard for diagnosis, an accurate questionnaire‐based algorithm to identify eligible subjects could facilitate efficient recruitment in research.Objective: This study aimed to optimize the identification of subjects with iRBD from the general population.Methods: Between June 2020 and July 2021, we placed newspaper advertisements, including the single‐question screen for RBD (RBD1Q). Participants' evaluations included a structured telephone screening consisting of the RBD screening questionnaire (RBDSQ) and additional sleep‐related questionnaires. We examined anamnestic information predicting PSG‐proven iRBD using logistic regressions and receiver operating characteristic curves.Results: Five hundred forty‐three participants answered the advertisements, and 185 subjects fulfilling inclusion and exclusion criteria were screened. Of these, 124 received PSG after expert selection, and 78 (62.9%) were diagnosed with iRBD. Selected items of the RBDSQ, the Pittsburgh Sleep Quality Index, the STOP‐Bang questionnaire, and age predicted iRBD with high accuracy in a multiple logistic regression model (area under the curve >80%). When comparing the algorithm to the sleep expert decision, 77 instead of 124 polysomnographies (62.1%) would have been carried out, and 63 (80.8%) iRBD patients would have been identified; 32 of 46 (69.6%) unnecessary PSG examinations could have been avoided.Conclusions: Our proposed algorithm displayed high diagnostic accuracy for PSG‐proven iRBD cost‐effectively and may be a convenient tool for research and clinical settings. External validation sets are warranted to prove reliability. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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 ( $p=0.018$ , ${\eta }_p^2=0.092$ ) and a statistical trend for overall executive functions ( $p=0.095$ , ${\eta }_p^2=0.132$ ). A statistical trend for a time × group interaction effect favoring CG was shown for the digit span backward as a working memory test ( $p=0.098$ , ${\eta }_p^2=0.043$ ). 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.

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.