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Background: Cognitive decline is a major reason for dependence and resource use in long-term care., Objective: We explored whether social activities may prevent cognitive decline of older residents of long-term care facilities., Methods: In a routine care cohort, 3,603 residents of long-term care facilities were assessed on average 4.4 times using the interRAI-Long-Term-Care-Facilities instrument which includes frequency of participation in social activities of long standing interest over the last 30 days and the Cognitive Performance Scale. Linear mixed models repeated measures analyses were performed corrected for age, sex, physical activity, Activities of Daily Living, mood, and health indicators., Results: Social activity was associated with cognitive preservation over time. This association was stronger in those with no or mild cognitive impairment at baseline, relative to those with moderate to severe impairment. Participation in specific social activities such as conversing and helping others showed a similar positive association. The relation between social activity and cognitive impairment appeared to be bi-directional., Conclusions: The protective effects of social activity offer a window of opportunity to preserve cognitive functioning in long-term care residents.

Background: To enable successful inclusion of electroencephalography (EEG) outcome measures in Alzheimer's disease (AD) clinical trials, we retrospectively mapped the progression of resting-state EEG measures over time in amyloid-positive patients with mild cognitive impairment (MCI) or dementia due to AD., Methods: Resting-state 21-channel EEG was recorded in 148 amyloid-positive AD patients (MCI, n = 88; dementia due to AD, n = 60). Two or more EEG recordings were available for all subjects. We computed whole-brain and regional relative power (i.e., theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-13 Hz), beta (13-30 Hz)), peak frequency, signal variability (i.e., theta permutation entropy), and functional connectivity values (i.e., alpha and beta corrected amplitude envelope correlation, theta phase lag index, weighted symbolic mutual information, inverted joint permutation entropy). Whole-group linear mixed effects models were used to model the development of EEG measures over time. Group-wise analysis was performed to investigate potential differences in change trajectories between the MCI and dementia subgroups. Finally, we estimated the minimum sample size required to detect different treatment effects (i.e., 50% less deterioration, stabilization, or 50% improvement) on the development of EEG measures over time, in hypothetical clinical trials of 1- or 2-year duration., Results: Whole-group analysis revealed significant regional and global oscillatory slowing over time (i.e., increased relative theta power, decreased beta power), with strongest effects for temporal and parieto-occipital regions. Disease severity at baseline influenced the EEG measures' rates of change, with fastest deterioration reported in MCI patients. Only AD dementia patients displayed a significant decrease of the parieto-occipital peak frequency and theta signal variability over time. We estimate that 2-year trials, focusing on amyloid-positive MCI patients, require 36 subjects per arm (2 arms, 1:1 randomization, 80% power) to detect a stabilizing treatment effect on temporal relative theta power., Conclusions: Resting-state EEG measures could facilitate early detection of treatment effects on neuronal function in AD patients. Their sensitivity depends on the region-of-interest and disease severity of the study population. Conventional spectral measures, particularly recorded from temporal regions, present sensitive AD treatment monitoring markers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Cognitive training (CT) has been proposed as a treatment option for cognitive impairment in Parkinson's disease (PD). We aimed to assess the efficacy of adaptive, computerized CT on cognitive function in PD., Methods: In this double-blind, randomized controlled trial we enrolled PD patients that experienced substantial subjective cognitive complaints. Over a period of eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control intervention for 45 min each (randomized 1:1). The primary outcome was the accuracy on the Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and analyzed with multivariate mixed-model analyses., Results: The intention-to-treat population consisted of 136 participants (n = 68 vs. n = 68, age M: 62.9y, female: 39.7%). Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance (n = 130): B: -0.06, 95% CI: -0.27 to 0.15, p = 0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 s) faster on difficulty load 4 of this task (secondary outcome): 95% CI: -0.55 to -0.06, p = 0.015. CT did not reduce subjective cognitive complaints. At follow-up, no group differences were found., Conclusions: This study shows no beneficial effect of eight-week computerized CT on the primary outcome (i.e., planning accuracy) and only minor improvements on secondary outcomes (i.e., processing speed) with limited clinical impact. Personalized or ecologically valid multi-modal intervention methods could be considered to achieve clinically meaningful and lasting effects., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Acute hospitalization may lead to posthospital syndrome, but no studies have investigated how this syndrome manifests and geriatric syndromes are often used as synonym. However, studies on longitudinal associations between syndromes and adverse outcomes are scarce. We aimed to analyze longitudinal associations between geriatric syndromes and functional decline (FD), readmission, and mortality., Methods: Prospective cohort study, including 401 acutely hospitalized patients (aged ≥ 70). We performed: (i) logistic regression analyses to assess associations between patterns of geriatric syndromes as they develop over time (between admission and 1 month postdischarge), and FD and readmission; (ii) generalized estimating equations to assess longitudinal associations between geriatric syndromes over five time points (admission, discharge, 1, 2, and 3 months postdischarge) and FD, mortality, and readmission at 3 months postdischarge., Results: After syndrome absent, syndrome present at both admission and 1 month postdischarge was most prevalent. Persistent patterns of apathy (odds ratio [OR] = 4.35, 95% confidence interval [CI] = 1.54-12.30), pain (OR = 3.26, 95% CI = 1.21-8.8), malnutrition (OR = 3.4, 95% CI = 1.35-8.56), mobility impairment (OR = 6.65, 95% CI = 1.98-22.38), and fear of falling (OR = 3.17, 95% CI = 1.25-8.02) were associated with FD. Developing cognitive impairment (OR = 6.40, 95% CI = 1.52-26.84), fatigue (OR = 4.71, 95% CI = 1.03-21.60), and fall risk (OR = 4.30, 95% CI = 1.21-16.57) postdischarge, was associated with readmission; however, only 4%-6% developed these syndromes. Over the course of five time points, mobility impairment, apathy, and incontinence were longitudinally associated with FD; apathy, malnutrition, fatigue, and fall risk with mortality; malnutrition with readmission., Conclusion: Most geriatric syndromes are present at admission and patients are likely to retain them postdischarge. Several geriatric syndromes are longitudinally associated with mortality and, particularly, persistently present syndromes place persons are at risk of FD. Although few persons develop syndromes postdischarge, those developing cognitive impairment, fatigue, and fall risk were at increased readmission risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Cognitive deficits affect up to 70% of all patients with Multiple Sclerosis (MS) and have a significant impact on quality of life. Cognitive assessments need to be performed by a neuropsychologist and are often time-consuming, hampering timely identification and adequate monitoring of cognitive decline in MS., Objective: To develop a time-efficient, unsupervised, digital tool to screen for cognitive deficits in MS., Methods: A digital (adjusted) version of the Brief International Cognitive Assessment for MS, including the Symbol Digit Modalities Test (SDMT, information processing speed), the California Verbal Learning Test (CVLT-II, verbal memory) and the Spatial Recall Test (SPART, visuospatial memory) was developed: Multiple Screener (intellectual property of Sanofi Genzyme). Firstly, the clarity and feasibility of the tool was confirmed by 16 patients with MS (mean age 50.9 years (SD 9.4, range 37-68). Next, in 60 healthy controls (HCs, mean age 44.5 years (SD 14.0, range 18-67), intraclass correlation coefficients (ICC) were calculated to describe how strongly the digital version resembled the paper and pencil-based assessment. Finally, 236 HCs (mean age 42.8 years (SD 12.8, range 18-69) were included to obtain norm scores for each test., Results: ICCs between digital and paper and pencil-based assessment were excellent to good (SDMT (ICC 0.79, confidence interval (CI) 0.67-0.87); CVLT-II (ICC 0.77, CI 0.64-0.85); SPART (ICC 0.61, CI 0.42-0.75)). For each test, a regression-based correction for the effect of age was applied on the raw scores before converting them to norm Z-scores. Additionally, the SDMT scores needed correction for education and the CVLT-II for education and sex (subgroups were created)., Conclusions: Performance on an adjusted, digital version of the BICAMS correlates highly with the standard paper-and-pencil based test scores in HCs. Multiple Screener is an unsupervised, digital tool, with available norm scores, ultimately allowing for easy monitoring of cognitive decline in patients with MS., Competing Interests: Declaration of Competing Interest L. van Dongen, B. Westerik, and J.W. Twisk have nothing to disclose with regard to this work. K. van der Hiele received honoraria for consultancies, presentations and advisory boards from Sanofi Genzyme and Merck Serono. L.H. Visser received honoraria for lectures, grants for research and honoraria for advisory boards from Sanofi Genzyme, Merck Serono, Novartis and Teva. M.M. Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen. L. Douw receives research support from Society in Science (Branco Weiss Fellowship). J.J.G. Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation and has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals. H.E. Hulst receives research support from the Dutch MS Research Foundation, grant number 12-548, and has received compensation for consulting services or speaker honoraria from Sanofi Genzyme, Merck Serono and Biogen Idec., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cognitive dysfunction is highly prevalent in Parkinson's disease (PD) and a large proportion of patients eventually develops PD-related dementia. Currently, no effective treatment is available. Cognitive training is effective in relieving cognitive dysfunctions in several -neurodegenerative- diseases, and earlier small-scale trials have shown positive results for PD. In this randomized controlled trial, we assess the efficacy of online home-based cognitive training, its long-term effects, as well as the underlying neural correlates in a large group of PD patients., Methods: In this double-blind randomized controlled trial we will include 140 non-demented patients with idiopathic PD that experience significant subjective cognitive complaints. Participants will be randomized into a cognitive training group and an active control group. In both groups, participants will individually perform an online home-based intervention for eight weeks, three times a week during 45 min. The cognitive training consists of thirteen games that focus on executive functions, attention and processing speed with an adaptive difficulty. The active control comprises three games that keep participants cognitively engaged without a training component. Participants will be subjected to extensive neuropsychological assessments at baseline and after the intervention, and at six months, one year and two years of follow-up. A subset of participants (40 in each treatment condition) will undergo structural and functional magnetic resonance imaging. The primary outcome of this study is the performance on the Tower of London task. Secondary outcomes are objective and subjective cognitive functioning, conversion to PD-related mild cognitive impairment or dementia, functional and structural connectivity and network topological indices measured with magnetic resonance imaging. None of the outcome measures are part of the cognitive training program. Data will be analyzed using multivariate mixed-model analyses and odds ratios., Discussion: This study is a large-scale cognitive training study in PD patients that evaluates the efficacy in relieving cognitive dysfunction, and the underlying mechanisms. The strengths of this study are the large sample size, the long follow-up period and the use of neuroimaging in a large subsample. The study is expected to have a low attrition and a high compliance rate given the home-based and easily-accessible intervention in both conditions., Trial Registration: ClinicalTrials.gov ID NCT02920632 . Registered September 30, 2016.

Longitudinal studies on the course of neurocognitive functioning of children with ADHD and their unaffected siblings are scarce. Also, it is unclear to what extent that course is related to ADHD outcomes. A carefully phenotyped large sample of 838 Caucasian participants (ADHD-combined type: n = 339, unaffected siblings: n = 271, controls: n = 228; mean age at baseline = 11.4 years, mean age at follow-up = 17.3 years, SD = 3.2) was used to investigate differences in the course of neurocognitive functioning of ADHD affected and unaffected siblings versus controls, and to investigate the relationship between neurocognitive change and ADHD outcomes. At baseline, an aggregated measure of overall neurocognitive functioning and eight neurocognitive measures of working memory, timing (speed/variability), motor control, and intelligence were investigated. Outcomes at follow-up were dimensional measures of ADHD symptom severity and the Kiddie-Global Assessment Scale (K-GAS) for overall functioning. At follow up, affected and unaffected siblings trended to, or fully caught up with performance levels of controls on four (44.4%) and five (55.6%) of the nine dependent variables, respectively. In contrast, performance in remaining key neurocognitive measures (i.e. verbal working memory, variability in responding) remained impaired at follow-up. Change in neurocognitive functioning was not related to ADHD outcomes. Our results question the etiological link between neurocognitive deficits and ADHD outcomes in adolescents and young adults.