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Abstract Background Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals’ quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention (“NeuroNation MED”) in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. Methods This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT (“NeuroNation MED”) for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. Discussion This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. Trial registration German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Abstract Background Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson’s disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD. Methods The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD. The intervention consists of a 5-week digital cognitive training accompanied by a module promoting a healthy, active lifestyle. In this monocentric, single-blinded, delayed-start randomized controlled trial, the intervention’s effectiveness will be evaluated compared to an initially passive control group that receives the intervention in the second, open-label phase of the study. Eighty individuals with iRBD confirmed by polysomnography will be consecutively recruited from the continuously expanding iRBD cohort at the University Hospital Cologne. The evaluation will focus on cognition and additional neuropsychological and motor variables. Furthermore, the study will examine the feasibility of the intervention, effects on physical activity assessed by accelerometry, and interrogate the intervention’s neural effects using magnetic resonance imaging and polysomnography. Besides, a healthy, age-matched control group (HC) will be examined at the first assessment time point, enabling a cross-sectional comparison between individuals with iRBD and HC. Discussion This study will provide insights into whether cognitive training and psychoeducation on a healthy, active lifestyle have short- and long-term (neuro-)protective effects for individuals with iRBD. Trial registration The study was prospectively registered in the German Clinical Trial Register (DRKS00024898) on 2022–03-11, https://drks.de/search/de/trial/DRKS00024898 . Protocol version: V5 2023–04-24.

Abstract Background Parkinson’s disease (PD) significantly impacts the health-related quality of life of affected individuals and their relatives. In order to support the affected individuals and their families in coping with PD, it is essential to offer comprehensive information about their experiences. A comprehensive understanding of their lived experiences with the disease, the healthcare system, applied self-management strategies and their needs is considered crucial for developing a PD support program. Therefore, we aimed to explore the lived experiences and support needs of individuals with PD and their relatives in Germany. Methods This non-interventional, qualitative study conducted an explorative status quo and needs assessment. It generated knowledge through semi-structured focus groups and interviews with individuals with PD at various disease stages and their relatives. The interviews were digitally recorded, transcribed verbatim, and analysed using content analysis. Results Fifty-two individuals with PD and 29 relatives participated in eight focus groups and 13 paired and 13 individual interviews. Four themes with corresponding subthemes emerged: (1) experiences, revealing individuals’ experiences around their diagnosis and with disease-specific care provision; (2) management support offers, clarifying who provides support and the type of support offered; (3) self-management, including comprehensibility, meaningfulness and manageability; and (4) future needs, differentiating between deficits and needs. Most participants expressed a sense of abandonment when obtaining self-management strategies and mastering their lives with PD, often referred to as ‘life 2.0’. They identified the lack of structured and adequate provision of information, system orientation and social awareness. Conclusions In Germany, there is an urgent need for a comprehensive PD care program that addresses the needs of individuals with PD and their relatives from the start of their care trajectory. It could assist individuals in gaining a comprehensive understanding of the disease, obtaining self-management strategies, building a support network, and becoming experts in self-managing their disease. Moreover, it may positively influence their care trajectory and reduce burdens, such as overburdening, fear of progression, and health anxiety. Trial Registration German Clinical Studies Register ( https://www.drks.de/DRKS00030090 , No. DRKS00030090, Date of registration: 15.12.2022).

Abstract Background Parkinson’s disease (PD) drastically affects motor and cognitive function, but evidence shows that motor-cognitive training improves disease symptoms. Motor-cognitive training in the home is scarcely investigated and eHealth methods can provide continual support for PD self-management. Feasibility testing is however required. Objective To assess the feasibility (i) Recruitment capability (ii) Acceptability and Suitability (iii) Demand and Safety of a home-based motor-cognitive eHealth exercise intervention in PD. Methods The 10-week intervention was delivered using the ExorLive® application and exercises were individually adapted and systematically progressed and targeted functional strength, cardiovascular fitness, flexibility, and motor-cognitive function. People with mild-to moderate PD were assessed before and after the intervention regarding; gait performance in single and dual-task conditions; functional mobility; dual-task performance; balance performance; physical activity level; health related quality of life and perceived balance confidence and walking ability; global cognition and executive function. Feasibility outcomes were continuously measured using a home-exercise diary and contact with a physiotherapist. Changes from pre- and post-intervention are reported descriptively. Results Fifteen participants (mean age 68.5 years) commenced and 14 completed the 10-week intervention. In relation to intervention Acceptability, 64% of the motor sessions and 52% of motor-cognitive sessions were rated as “enjoyable”. Concerning Suitability, the average level of exertion (Borg RPE scale) was light (11–12). Adherence was high, with 86% of all (420) sessions reported as completed. No falls or other adverse events occurred in conjunction with the intervention. Conclusions This motor-cognitive eHealth home exercise intervention for PD was safe and feasible in terms of Recruitment capability, Acceptability, Safety and Demand. The intensity of physical challenge needs to be increased before testing in an efficacy trial. Trial registration This trial is registered at Clinicaltrials.gov (NCT05027620).

Introduction Based on the available evidence, cognitive stimulation is recommended as an intervention for people with dementia (PwD). Currently, cognitive stimulation is regularly offered as a group programme in care facilities. However, some residents, such as those who are bedridden, cannot participate. Furthermore, group programmes were not feasible during the pandemic. A concept that accompanies everyday life and enables cognitive stimulation in everyday communication (ie, ‘24/7’) has been missing. Therefore, this feasibility study aims to (1) assess the feasibility of a new continuous 24/7 cognitive stimulation programme (CogStim24) based on a process evaluation and (2) examine the possible effects of CogStim24 on the primary outcome of global cognition in PwD and further PwD-related and staff-related outcomes.Methods and analysis The complex CogStim24 programme is developed to be conducted as an everyday intervention during routine care including cognitively stimulating techniques, such as reminiscence therapy, multisensory stimulation and physical activity. In this unblinded single-arm study with pre-assessments and post-assessments, four nursing homes with a total of N=20 nursing and care staff will participate in an 11-week CogStim24 training programme. The intervention will be conducted to N=60 PwD. Neuropsychological assessments will be conducted pre-staff and post-staff training, as well as after a 6-week implementation phase. A process evaluation will be performed.Ethics and dissemination Ethics approval was obtained from the ethics committee of the Faculty of Medicine of the University of Cologne, Cologne, Germany. Although cognitive stimulation is known to be effective for enhancing global cognition and quality of life in PwD, it is currently undersupplied to PwD. Therefore, CogStim24 has the potential to reach many more PwD. This study has the potential to serve as a basis for a large multicentre cluster randomised controlled trial. An interdisciplinarity team and mixed-methods approach will help generate information on the practicality and mechanisms of impact of CogStim24. This is important for the further development of the intervention and for facilitating its implementation. The study results will be disseminated via presentations at scientific conferences and meetings for healthcare professionals and PwD and their relatives. Several manuscripts presenting results of the different study parts will be published in peer-reviewed journals.Trial registration number DRKS00024381.

Abstract With increasing numbers of older prisoners, effective strategies for preventing and treating age-associated diseases, such as cognitive disorders, are needed. As pharmacological therapies are limited, non-pharmacological interventions are increasingly recognized as potential treatment strategies. One approach is cognitive training (CT). However, no study has investigated CT in the prison setting. Thus, this one-arm feasibility trial aims to analyze the feasibility of (i) the study protocol and (ii) the implementation of multimodal CT for older prisoners. Eighteen older male prisoners from two specific divisions for older prisoner participated in 12 weekly CT sessions using the NEUROvitalis program. The feasibility analysis included recruitment, dropout, and CT participation rates, and motivation for and satisfaction with CT (using 6-point Likert-scales). The study protocol demonstrated sufficient feasibility with high recruitment rates between 46 and 50%. Therefore, the CT implementation was successful: Only one prisoner ceased participation; all others completed the CT sessions (i.e., attended > 75% of the sessions). Prisoners reported high CT motivation and satisfaction, and would recommend CT. This is the first study to demonstrate CT feasibility in older prisoners. Although more research is needed, these results are a starting point for expanding services to include cognitively enhancing activities for older prisoners. This one-arm feasibility study was pre-registered in the German Clinical Trials Register (DRKS; ID: DRKS00020227).), Registered 11 Mai 2021 https://drks.de/search/de/trial/DRKS00020227 .

Abstract Background Electronic health (eHealth) technology offers the potential to support and motivate physical activity for symptom management in Parkinson’s disease (PD). It is also recommended that motor exercise in PD be complemented with cognitive training aimed at attentional or executive functions. This paper describes the protocol for a double-blind randomized controlled trial to evaluate the effects of motor-cognitive training in the home environment, supported by eHealth. Methods/design The Support for home Training using Ehealth in Parkinsons diseaSe (STEPS) is a double-blind single center randomized controlled trial. Two parallel groups will include in total 120 participants with mild to moderate PD who will receive either (i) the intervention (a progressive 10-week individualized motor-cognitive eHealth training with cognitive behavioral elements to increase physical activity levels) or (ii) an active control group (an individualized 10-week paper-based home exercise program). The active control group will not receive motor-cognitive exercises or cognitive behavioral approaches to increase physical activity level. The primary outcome is walking capacity assessed by the six-minute walk test (6MWT). Secondary outcomes will include gait performance during single and dual task conditions, gait speed, functional mobility and lower limb strength, balance, physical activity behavior and a range of patient reported outcome measures relevant in PD. Discussion The STEPS trial will answer the question whether 10 weeks of eHealth supported motor-cognitive exercise in the home environment can improve walking capacity in PD when compared to a standard paper exercise program. Findings from this study will also strengthen the evidence concerning the efficacy of PD-specific eHealth interventions with a view meeting future health care demands by addressing issues of inaccessibility to specialized neurological rehabilitation in PD. Trial registration ClinicalTrials.gov August 2022, NCT 05510739.

Abstract Background Cognitive decline is a major factor for the deterioration of the quality of life in patients suffering from Parkinson’s disease (PD). Recently, it was reported that cognitive training (CT) in PD patients with mild cognitive impairment (PD-MCI) led to an increase of physical activity (PA) accompanied by improved executive function (EF). Moreover, PA has been shown to alter positively brain function and cognitive abilities in PD. Both observations suggest an interaction between CT and PA. Objectives A previous multicenter (MC) study was slightly significant when considering independent effects of interventions (CT and PA) on EF. Here, we use MC constituent single center data that showed no effect of interventions on EF. Thus, this exploratory study considers pooling data from both interventions to gain insight into a recently reported interaction between CT and PA and provide a proof of principle for the usefulness of resting state EEG as a neurophysiological biomarker of joint intervention’s effect on EF and attention in PD-MCI. Methods Pre- and post-intervention resting state EEG and neuropsychological scores (EF and attention) were obtained from 19 PD-MCI patients (10 (CT) and 9 (PA)). We focused our EEG analysis on frontal cortical areas due to their relevance on cognitive function. Results We found a significant joint effect of interventions on EF and a trend on attention, as well as trends for the negative correlation between attention and theta power (pre), the positive correlation between EF and alpha power (post) and a significant negative relationship between attention and theta power over time (post-pre). Conclusions Our results support the role of theta and alpha power at frontal areas as a biomarker for the therapeutic joint effect of interventions.

IntroductionCorrectional institutions are challenged by increasing numbers of older prisoners. Existing literature highlights the vulnerability of this group that is reflected by various somatic and mental health issues including cognitive dysfunctions. Although cognitive training studies in various target groups of older people have been conducted, there is lack of data regarding cognitive training in older prisoners. A structured cognitive group training program (“NEUROvitalis Prison”) with 12 weekly sessions was offered to male prisoners in Germany.MethodsPost intervention an exploratory qualitative study was conducted. Prisoners (N = 18) and staff (N = 4) perspectives were explored by conducting face-to-face semi-structured interviews. Audiotaped data were fully transcribed and deductive-inductive content analyses applied.ResultsBoth the prisoners and the staff perceived the cognitive training as very positive and stimulating. Moreover, the importance of the training was pronounced in terms of an increase in self-esteem and understanding of cognition and aging in the prisoners.DiscussionOur data indicate that cognitive training may be a feasible and valuable intervention for older prisoners that will be appreciated by both inmates and staff. The qualitative data provide substantial insight into the experiences with the applied cognitive training program. Moreover, valuable modifications for future conduct can be derived.

Background: Sexual minority individuals experience discrimination, leading to mental health disparities. Physical health disparities have not been examined to the same extent in systematic reviews so far. Objectives: To provide a systematic review and, where possible, meta-analyses on the prevalence of physical health conditions in sexual minority women (i.e. lesbian- and bisexual-identified women) compared to heterosexual-identified women. Design: The study design is a systematic review with meta-analyses. Data Sources and Methods: A systematic literature search in MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science databases was conducted on epidemiologic studies on physical health conditions, classified in the Global Burden of Disease project, published between 2000 and 2021. Meta-analyses pooling odds ratios were calculated. Results: In total, 23,649 abstracts were screened and 44 studies were included in the systematic review. Meta-analyses were run for arthritis, asthma, back pain, cancer, chronic kidney diseases, diabetes, headache disorders, heart attacks, hepatitis, hypertension, and stroke. Most significant differences in prevalence by sexual identity were found for chronic respiratory conditions, especially asthma. Overall, sexual minority women were significantly 1.5–2 times more likely to have asthma than heterosexual women. Furthermore, evidence of higher prevalence in sexual minority compared to heterosexual women was found for back pain, headaches/migraines, hepatitis B/C, periodontitis, urinary tract infections, and acne. In contrast, bisexual women had lower cancer rates. Overall, sexual minority women had lower odds of heart attacks, diabetes, and hypertension than heterosexual women (in terms of diabetes and hypertension possibly due to non-consideration of pregnancy-related conditions). Conclusion: We found evidence for physical health disparities by sexual identity. Since some of these findings rely on few comparisons only, this review emphasizes the need for routinely including sexual identity assessment in health research and clinical practice. Providing a more detailed picture of the prevalence of physical health conditions in sexual minority women may ultimately contribute to reducing health disparities.

Background: Dementia with Lewy bodies (DLB) is an important cause of dementia with a range of clinical manifestations, including motor, neuropsychiatric, and autonomic symptoms. Compared with more common forms of dementia such as Alzheimer’s disease, DLB has been the focus of significantly fewer treatment studies, often with diverse outcome measures, making comparison and clinical implementation difficult. A core outcome set (COS) can address this by ensuring that data are comparable, relevant, useful, and usable for making the best healthcare decisions. Methods: Using a multi-stage approach, development of the DLB-COS will include the following stages: (1) A systematic review, following PRISMA guidelines to create an initial long list of outcomes; (2) A two-round online Delphi including clinicians, scientists, policymakers, and individuals with lived experience of DLB and their representatives; (3) An online consensus meeting to agree on the final core list of outcomes (the final DLB-COS) for use in research and clinical practice; (4) A literature search to identify appropriate measurement instruments for the DLB-COS outcomes; (5) A final consensus meeting of the professional stakeholders who attended the online consensus meeting to agree on the instruments that should be used to measure the outcomes in the DLB-COS; and (6) Global dissemination. Discussion: This is a multi-stage project to develop a COS to be used in treatment trials for DLB. A DLB-COS will ensure the selection of relevant outcomes and will identify the instruments to be used to measure DLB globally.

BackgroundDue to the increasing prevalence of Alzheimer’s disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise.ObjectivesHere, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST.MethodsUsing neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15).ResultsAfter CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus.ConclusionOur data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.

Abstract Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson’s disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015–09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford’s Royal Hospital Manchester, and King’s College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56–0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03–1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48–1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.

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

Abstract Background Effective communication is a central aspect of organizational health literacy. Healthcare professionals are expected to ensure an effective and satisfactory flow of information and to support their patients in accessing, understanding, appraising, and applying health information. This qualitative study aimed to examine the health literacy-related challenges, needs, and applied solutions of healthcare professionals when engaging with persons with a migrant background. Based on the integrated model of health literacy (Sørensen et al., BMC Public Health 12:80, 2012), we focused on environmental, personal, and situational factors that shape health literacy in transcultural treatment settings. Methods We conducted five focus group discussions with healthcare professionals (N = 31) who are in regular contact with persons with a migrant background. Discussions were transcribed verbatim and analyzed using qualitative content analysis by applying a deductive–inductive categorization procedure. Deductive categories were derived from the integrated model of health literacy. Results Challenges included a mismatch in the provision and use of health services. Participants regarded easily accessible services and outreach counselling as helpful solutions. Further challenges were the migrant patients’ distrust in healthcare professionals and the German healthcare system, the participants’ uncertainty in dealing with patients’ expectations and needs, and the patients’ non-compliance with appointments. Environmental factors included systemic lack of time and economic pressure. Both were reported as impeding the flow of information in all treatment settings. Participants with a migrant background themselves (n = 16) regarded this personal factor as an opportunity that increased patients’ trust in them. They also reported challenges such as high levels of responsibility felt when ad hoc interpreting for colleagues. Conclusions Known issues observed in the delivery of healthcare for the majority population (i.e., systemic lack of time, economic pressure) appear to be intensified in the context of migration. An increasingly diverse patient clientele indicates a growing need for culture-sensitive, health-literate healthcare organizations. A corresponding diversity of the health workforce is desirable and should be strengthened by national finance and educational programs. Healthcare professionals who interpret for colleagues should be given the necessary time. Further studies are needed to develop appropriate interventions for improving health literacy at individual and organizational levels. Funding for interpreting services should be expanded.

Background: Dementia with Lewy bodies (DLB) is an important cause of dementia with a range of clinical manifestations, including motor, neuropsychiatric, and autonomic symptoms. Compared with more common forms of dementia such as Alzheimer’s disease, DLB has been the focus of significantly fewer treatment studies, often with diverse outcome measures, making comparison and clinical implementation difficult. A core outcome set (COS) can address this by ensuring that data are comparable, relevant, useful, and usable for making the best healthcare decisions. Methods: Using a multi-stage approach, development of the DLB-COS will include the following stages: (1) A systematic review, following PRISMA guidelines to create an initial long list of outcomes; (2) A two-round online Delphi including clinicians, scientists, policymakers, and individuals with lived experience of DLB and their representatives; (3) An online consensus meeting to agree on the final core list of outcomes (the final DLB-COS) for use in research and clinical practice; (4) A literature search to identify appropriate measurement instruments for the DLB-COS outcomes; (5) A final consensus meeting of the professional stakeholders who attended the online consensus meeting to agree on the instruments that should be used to measure the outcomes in the DLB-COS; and (6) Global dissemination. Discussion: This is a multi-stage project to develop a COS to be used in treatment trials for DLB. A DLB-COS will ensure the selection of relevant outcomes and will identify the instruments to be used to measure DLB globally.

Objective To investigate gender differences of health literacy in individuals with a migration background.Design Systematic review and meta-analysis. OVID/MEDLINE, PsycINFO and CINAHL were searched in March 2018 and July 2020.Setting Studies had to provide health literacy data for adult women and men with a migration background, collected with a standardised instrument, or report results that demonstrated the collection of such data. Health literacy data were extracted from eligible studies or requested from the respective authors. Using a random-effects model, a meta-analysis was conducted to assess standardised mean differences (SMDs) of health literacy in men and women. Two researchers independently assessed risk of bias for each included study using the Appraisal Tool for Cross-Sectional Studies.Results Twenty-four studies were included in this systematic review. Thereof, 22 studies (8012 female and 5380 male participants) were included in the meta-analyses. In six studies, gender-specific health literacy scores were reported. The authors of additional 15 studies provided their data upon request and for one further study data were available online. Women achieved higher health literacy scores than men: SMD=0.08, 95% CI 0.002 to 0.159, p=0.04, I2=65%. Another 27 studies reported data on female participants only and could not be included due to a lack of comparable studies with male participants only. Authors of 56 other eligible studies were asked for data, but without success.Conclusion Men with a migration background—while being much less frequently examined—may have lower health literacy than women. As heterogeneity between studies was high and the difference became statistically insignificant when excluding studies with a high risk of bias, this result must be interpreted with caution. There is a paucity of research on the social and relational aspects of gender in relation to health literacy among people with a migration background, especially for men.PROSPERO registration number CRD42018085555.

Background: Multiple sclerosis (MS) is a chronic neurological disease with an uncertain course. Wisdom and self-management are skills that can be used to cope with uncertainty and unpredictable life stresses. The present study aims to identify relevant wisdom and self-management skills for coping with fear of progression (FoP), a widely underdiagnosed real-life fear in response to uncertainty and a risk factor for depression and anxiety in patients with MS (PwMS). Methods: Ninety-two German inpatients aged 24–64 years with predominantly relapsing–remitting MS (72,8%) were included in this study. Correlation analyses and blockwise regression analyses were conducted to evaluate the relationship between wisdom skills (Self-Assessed Wisdom Scale, SAWS) and self-management skills (Questionnaire to Assess Resources and Self-management Skills, FERUS) with FoP (Fear of Progression-Questionnaire, FoP-Q), while controlling for demographic and disease-related variables. Results: Blockwise regression analyses (BRA) revealed the following significant unique predictions for each FoP-Q subscale: age (R change = 0.043), emotional regulation (0.028), and self-efficacy (0.029) on affective reaction; age (0.087) on partnership/family; age (0.055) and self-observation (0.043) on occupation; age (0.040), fatigue (0.057), and self-observation (0.039) on loss of autonomy. Limitations: The cross-sectional design, lack of comparison groups, and exclusive use of self-reports limit the generalizability of this study. Conclusions: Age is the strongest predictor for FoP-Q. Emotional regulation (as wisdom skills), self-observation and self-efficacy (as self-management skills), and fatigue are critical factors in dealing with specific aspects of FoP for PwMS. Larger, prospective, and longitudinal designed studies are needed to specify and replicate the results.

Abstract Background The goal is to investigate prognostic factors for change in memory test performance in healthy older adults and to report and discuss the different statistical procedures used for investigating this topic in the literature. Methods Prognostic factors were here understood as any measures that were investigated to estimate change in memory test performance. MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched up to November 2019. Prognostic factor and prognostic factor finding studies investigating prognostic factors on verbal and non-verbal short- and long-term memory after conducting memory training in healthy older adults were included. Risk of bias was assessed using the QUIPS tool. Results Our search yielded 12,974 results. We included 29 studies that address prognostic factors of change in memory test performance, including sociodemographic, (neuro-)psychological, genetic, and biological parameters. Studies showed high variation and methodological shortcomings with regard to the assessment, statistical evaluation, and reporting of the investigated prognostic factors. Included studies used different types of dependent variables (change scores vs. post-test scores) when defining change in memory test performance leading to contradictory results. Age was the only variable investigated throughout most of the studies, showing that older adults benefit more from training when using the change score as the dependent variable. Conclusion Overall, there is a need for adequate reporting in studies of prognostic factors for change in memory test performance. Because of inconsistencies and methodological shortcomings in the literature, conclusions regarding prognostic factors remain uncertain. As a tentative conclusion, one may say that the higher the age of the participant, the more profound the improvement in memory test performance will be after memory training. Trial registration CRD42019127479 .

ObjectiveParkinson's Disease (PD) is associated with both motor and non-motor problems, such as cognitive impairment. Particular focus in this area has been on the relationship between language impairment and decline in other cognitive functions, with the literature currently inconclusive on how the nature and degree of language impairment relate to cognition or other measures of disease severity. In addition, little information is available on how language problems identified in experimental task set-ups relate to competency in self-generated language paradigms such as picture description, monologues or conversations. This study aimed to inform clinical management of language impairment in PD by exploring (1) language performance across a range of experimental as well as self-generated language tasks, (2) how the relationship between these two aspects might be affected by the nature of the cognitive and language assessment; and (3) to what degree performance can be predicted across the language tasks.Methods22 non-demented people with PD (PwPD) and 22 healthy control participants performed a range of cognitive and language tasks. Cognitive tasks included a screening assessment in addition to tests for set shifting, short term memory, attention, as well as letter and category fluency. Language was investigated in highly controlled grammar tasks as well as a Sentence Generation and a Narrative.ResultsThe study highlighted impaired ability in set-shifting and letter fluency in the executive function tasks, and a higher rate of grammatical and lexical errors across all language tasks in the PD group. The performance in the grammar task was linked to set shifting ability, but error rates in Sentence Generation and Narrative were independent of this. There was no relevant relationship between performances across the three language tasks.ConclusionsOur results suggest that there is a link between executive function and language performance, but that this is task dependent in non-demented PwPD. This has implications for the management of language impairment in PD, both for assessment and for designing effective interventions.

Abstract Objectives To investigate the course of activities of daily living (IADL) functioning and possible predictors of performance changes in healthy older adults conducting either a General Cognitive Training (GCT) or a Reasoning Cognitive Training (ReaCT) or no training (control group, CG) over a period of 6 weeks, 3 months, and 6 months. Setting and participants An online, home‐based GCT and ReaCT including n = 2913 healthy participants (GCT: n = 1096; ReaCT: n = 1022; CG: n = 794) aged 60 years and older. Methods Multilevel analysis were calculated to explore the nature of our outcome variables of IADL part A (independence) and part B (difficulty of tasks), and to detect possible predictors for participants’ performance on IADL after CT. Results The random slopes models fitted better for the outcomes IADL Part B in the GCT group (χ2(2) = 18.78, p

Abstract 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.

Abstract Objective The goal of this contribution is to gather and to critically analyze recent evidence regarding the potential of exergaming for Parkinson’s disease (PD) rehabilitation and to provide an up-to-date analysis of the current state of studies on exergame-based therapy in PD patients. Methods We performed our search based on the conclusions of a previous systematic review published in 2014. Inclusion criteria were articles published in the indexed databases Pubmed, Scopus, Sciencedirect, IEEE and Cochrane published since January 1, 2014. Exclusion criteria were papers with a target group other than PD patients exclusively, or contributions not based on exergames. Sixty-four publications out of 525 matches were selected. Results The analysis of the 64 selected publications confirmed the putative improvement in motor skills suggested by the results of the previous review. The reliability and safety of both Microsoft Kinect and Wii Balance Board in the proposed scenarios was further confirmed by several recent studies. Clinical trials present better (n = 5) or similar (n = 3) results than control groups (traditional rehabilitation or regular exercise) in motor (TUG, BBS) and cognitive (attention, alertness, working memory, executive function), thus emphasizing the potential of exergames in PD. Pilot studies (n = 11) stated the safety and feasibility of both Microsoft Kinect and Wii Balance Board, potentially in home scenarios as well. Technical papers (n = 30) stated the reliability of balance and gait data captured by both devices. Related meta-analyses and systematic reviews (n = 15) further support these statements, generally citing the need for adaptation to patient’s skills and new input devices and sensors as identified gaps. Conclusion Recent evidence indicates exergame-based therapy has been widely proven to be feasible, safe, and at least as effective as traditional PD rehabilitation. Further insight into new sensors, best practices and different cognitive stadiums of PD (such as PD with Mild Cognitive Impairment), as well as task specificity, are required. Also, studies linking game parameters and results with traditional assessment methods, such as UPDRS scores, are required. Outcomes for randomized controlled trials (RCTs) should be standardized, and follow-up studies are required, particularly for motor outcomes.

Background: Cognitive Training (CT) may contribute to the maintenance and even enhancement of cognitive functions in healthy older adults. However, the question who benefits most from multi-domain CTs is still highly under-investigated.Objective: The goal is to investigate prognostic factors and models for changes in cognitive test performance in healthy older adults after a multi-domain CT.Methods: The data bases MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched up to July 2019. Studies investigating prognostic factors and/or models on cognitive outcomes (global cognition, memory, attention, executive functions, language, visuo-spatial abilities) after conducting a multi-domain CT in healthy older adults were included. Risk of Bias was assessed using the QUIPS and the PROBAST tool.Results: 23 prognostic factor and model studies were included. Results indicate a high heterogeneity regarding the conducted multi-domain CTs, the investigated prognostic factors, the investigated outcomes, and the used statistical approaches. Age and neuropsychological performance at study entry were the most investigated predictors, yet they show inconsistent results.Conclusion: Data on prognostic factors and models of changes after multi-domain CT are still too rare and inconsistent to draw clear conclusions due to statistical shortcomings and low reporting quality. Approaches for future research are outlined.Registration:https://www.crd.york.ac.uk/prospero/, ID: CRD42020147531

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.

Abstract 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.

Abstract Objectives To investigate predictors of performance changes and their time course in healthy older adults. Design A post hoc analysis of a RCT investigating the effect of reasoning cognitive training (ReaCT) compared to an active control group (CG) during a time course. Setting and participants An online, home‐based RCT including n = 4,310 healthy participants (ReaCT: n = 2,557; CG: n = 1,753) aged 50 years and older. Methods Multiple regression analyses were conducted to investigate predictors (age, sex, education, severity of depression, number of training sessions the participants attended, and neuropsychological baseline values) of the outcome measures grammatical reasoning, working memory, digit vigilance, verbal short‐term memory, and verbal learning at 6 weeks, 3, and 6 months. Results Being female and lower education predicted improvements in grammatical reasoning scores at 6 weeks and 3 months of training. Conclusion and implication Identifying predictors for nonpharmacological interventions may help to set up a personalized medicine approach in order to prevent cognitive decline in healthy older adults.

Research on support for relatives of patients with Parkinsonism has mainly focused on caregivers, while preventive offers for non-caregiving relatives are lacking. Thus, the aim of this multicenter pilot study is to develop and assess the feasibility of a preventive psychosocial support program for relatives of patients with Parkinsonism. It specifically focuses on family members of patients who are in an early phase of the disease, are not currently caregiving, and have not yet developed distress symptoms. It includes a telemedicine-based, 6-week preventive psychological short intervention (PPSI). The main objective of this feasibility mixed-methods study is to specify the demand for an early, low-threshold, and low-cost short intervention and to collect feedback based on qualitative and quantitative data of N = 20 relatives. Secondary objectives are an evaluation of the effects of the intervention and an analysis of the study design. Future directions are to further develop the PPSI using these data. This study can serve as a basis for future randomized controlled studies on this intervention, which might fill an important gap in clinical supply.

Cognitive integrity has a multifactorial basis and is essential for quality of life and wellbeing. Several lifestyle programs including those using cognitive training have been developed in the past recent years to preserve cognitive health, but there is still debate about the most effective strategy to be used. We retrospectively analyzed data from 289 healthy participants of the BrainProtect® cognitive training program, developed by the German Association for Memory Training (Bundesverband Gedächtnistraining e.V.). Eight weekly 90- minute sessions of cognitive exercises were holistically structured to include physical exercises and nutrition counseling basing upon social interaction. The large majority (79.9%) of the participants showed improved cognitive scores after the intervention with respect to the baseline, with more than 10/69 points gained. Almost 60% felt their cognitive efficiency increased and an average increase in all cognitive domain explored could be observed. This retrospective analysis of preliminary data suggests that BrainProtect® might improve mental fitness after 8 weeks of multidomain cognition-centered training. These encouraging results need to be confirmed in further randomized studies.

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: 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.

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, ηp2=0.092) and a statistical trend for overall executive functions (p=0.095, ηp2=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, ηp2=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.

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. Trial registration: German Clinical Trial Register (drks.de, DRKS00009379)

Background: The nonmotor symptom spectrum of Parkinson’s disease (PD) includes progressive cognitive decline mainly in late stages of the disease. The aim of this study was to map the patterns of altered structural connectivity of patients with PD with different cognitive profiles ranging from cognitively unimpaired to PD-associated dementia. Methods: Diffusion tensor imaging and neuropsychological data from the observational multicentre LANDSCAPE study were analyzed. A total of 134 patients with PD with normal cognitive function (56 PD-N), mild cognitive impairment (67 PD-MCI), and dementia (11 PD-D) as well as 72 healthy controls were subjected to whole-brain-based fractional anisotropy mapping and covariance analysis with cognitive performance measures. Results: Structural data indicated subtle changes in the corpus callosum and thalamic radiation in PD-N, whereas severe white matter impairment was observed in both PD-MCI and PD-D patients including anterior and inferior fronto-occipital, uncinate, insular cortices, superior longitudinal fasciculi, corona radiata, and the body of the corpus callosum. These regional alterations were demonstrated for PD-MCI and were more pronounced in PD-D. The pattern of involved regions was significantly correlated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total score. Conclusions: The findings in PD-N suggest impaired cross-hemispherical white matter connectivity that can apparently be compensated for. More pronounced involvement of the corpus callosum as demonstrated for PD-MCI together with affection of fronto-parieto-temporal structural connectivity seems to lead to gradual disruption of cognition-related cortico-cortical networks and to be associated with the onset of overt cognitive deficits. The increase of regional white matter damage appears to be associated with the development of PD-associated dementia.

Background: Combining cognitive training (CT) with physical activity (CPT) has been suggested to be most effective in maintaining cognition in healthy older adults, but data are scarce and inconsistent regarding long-term effects (follow-up; FU) and predictors of success.Objective: To investigate the 1-year FU effects of CPT versus CT and CPT plus counseling (CPT+C), and to identify predictors for CPT success at FU.Setting and Participants: We included 55 healthy older participants in the data analyses; 18 participants (CPT group) were used for the predictor analysis.Interventions: In a randomized controlled trial, participants conducted a CT, CPT, or CPT+C for 7 weeks.Outcome Measures: Overall cognition, verbal, figural, and working memory, verbal fluency, attention, planning, and visuo-construction.Results: While within-group comparisons showed cognitive improvements for all types of training, only one significant interaction Group × Time favoring CPT in comparison to CPT+C was found for overall cognition and verbal long-term memory. The most consistent predictor for CPT success (in verbal short-term memory, verbal fluency, attention) was an initial low baseline performance. Lower education predicted working memory gains. Higher levels of insulin-like growth factor 1 (IGF-1) and lower levels of brain-derived neurotrophic factor at baseline (BDNF) predicted alternating letter verbal fluency gains.Discussion: Within-group comparisons indicate that all used training types are helpful to maintain cognition. The fact that cognitive and sociodemographic data as well as nerve growth factors predict long-term benefits of CPT contributes to the understanding of the mechanisms underlying training success and may ultimately help to adapt training to individual profiles.Clinical Trial Registration: WHO ICTRP (http://apps.who.int/trialsearch/), identifier DRKS00005194.

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.

BACKGROUND:Given the high prevalence of cognitive impairment in Parkinson's disease (PD), cognitive screening is important in clinical practice. The Montreal Cognitive Assessment (MoCA) is a frequently used screening test in PD to detect mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PD-D). However, the proportion in which the subtests are represented in the MoCA total score does not seem reasonable. We present the development and preliminary evaluation of an empirically based alternative scoring system of the MoCA which aims at increasing the overall diagnostic accuracy. METHODS:In study 1, the MoCA was administered to 40 patients with PD without cognitive impairment (PD-N), PD-MCI, or PD-D, as defined by a comprehensive neuropsychological test battery. The new MoCA scoring algorithm was developed by defining Areas under the Curve (AUC) for MoCA subtests in a Receiver Operating Characteristic (ROC) and by weighting the subtests according to their sensitivities and specificities. In study 2, an independent sample of 24 PD patients (PD-N, PD-MCI, or PD-D) was tested with the MoCA. In both studies, diagnostic accuracy of the original and the new scoring procedure was calculated. RESULTS:Diagnostic accuracy increased with the new MoCA scoring algorithm. In study 1, the sensitivity to detect cognitive impairment increased from 62.5% to 92%, while specificity decreased only slightly from 77.7% to 73%; in study 2, sensitivity increased from 68.8% to 81.3%, while specificity stayed stable at 75%. CONCLUSION:This pilot study demonstrates that the sensitivity of the MoCA can be enhanced substantially by an empirically based weighting procedure and that the proposed scoring algorithm may serve the MoCA's actual purpose as a screening tool in the detection of cognitive dysfunction in PD patients better than the original scoring of the MoCA. Further research with larger sample sizes is necessary to establish efficacy of the alternate scoring system.

A high percentage of Parkinson’s disease (PD) patients show cognitive impairments in addition to the cardinal motor symptoms. These deficits primarily concern executive functions most probably linked to dysfunctions in prefrontal regions due to decreased dopaminergic transmission in fronto-striatal loops. To investigate possible associations between decision-making and executive functions in PD, we examined 20 non-demented PD patients and 20 healthy control subjects with a neuropsychological test battery and the Game of Dice Task. In this computerised decision-making task, the rules for gains and losses and the winning probabilities are obvious and stable. Thus, strategic components besides feedback processing might influence decision-making in this task. We found that PD patients were impaired in the Game of Dice task performance and that the frequency of disadvantageous choices correlated with both executive functions and feedback processing. We suggest that decision-making deficits of PD patients in explicit gambling situations might be associated with dysfunctions in two different fronto-striatal loops: the limbic-orbitofrontal-striatal loop, involved in feedback processing, and the dorsolateral prefrontal-striatal loop, involved in executive functions.