Importance:Impairment of working memory (WM), which relies on distributed cortical and subcortical structures, including cerebello-striatal pathways, is a core contributor to functional decline in patients with mild cognitive impairment (MCI) and dementia. Because the striatum is affected early in dementia, whereas the cerebellum remains relatively preserved, the cerebellum may offer support for maintaining striatal function in neurodegenerative diseases. Objective:To evaluate whether sequential cerebellar transcranial magnetic stimulation (TMS) and striatal transcranial temporal interference stimulation (tTIS) enhances WM in patients with MCI, especially those with early striatal degeneration, like MCI with Lewy bodies (MCI-LB). Design, Setting, and Participants:This randomized, quadruple-blind, placebo-controlled, crossover trial was conducted from August 2023 to October 2024 at 1 site in Switzerland and 1 in Czech Republic. Participants included individuals with MCI-LB or amnestic MCI (aMCI) and age-matched healthy controls (HCs). Intervention:Three pseudorandomized single stimulation sessions: (1) cerebellar TMS followed by striatal tTIS, (2) control TMS followed by striatal tTIS, and (3) an active control combining control TMS with control striatal tTIS. Main Outcomes and Measures:The primary outcomes were changes in accuracy and correct answer reaction times in a visual WM task with varying memory loads and distractors. Modulators included resting-state functional connectivity and gray-matter volume in WM-related regions. Linear mixed-effects models were used to examine the main effects of stimulation condition on accuracy and reaction times. Results:Forty-one patients with MCI, including 21 with MCI-LB (16 female [76%]; mean [SD] age, 71.05 [6.84] years) and 20 with aMCI (11 female [55%]; mean [SD] age, 72.30 [7.50] years), and 20 HCs (10 female [50%]; mean [SD] age, 69.5 [4.42] years) were analyzed. In patients with MCI-LB, cerebellar TMS plus striatal tTIS increased accuracy in distractor trials compared with the active control (control TMS plus control tTIS, P < .001; d = -0.77) and striatal tTIS alone (control TMS plus striatal tTIS, P = .004; d = -0.60). Greater accuracy gains were associated with lower putaminal connectivity (r = -0.66; P = .03). In patients with aMCI, cerebellar volumes showed associations with task performance in both distractor trials (cerebellar TMS plus striatal tTIS, R2 = 0.27; P = .02) and high-load trials (control TMS plus striatal tTIS, R2 = 0.24; P = .03), and larger volumes were associated with faster responses; however, significant behavioral differences between active and control stimulation conditions were not observed. No serious adverse events occurred. Conclusions and Relevance:Synergistic dual-target cerebellar TMS and striatal tTIS improved WM in MCI-LB, particularly in patients with lower striatal connectivity, suggesting dual-targeted neuromodulation as a potential therapeutic avenue in neurodegenerative disorders. Trial Registration:ClinicalTrials.gov Identifier: NCT07090681.
ABSTRACT:The Swiss Spinal Cord Injury Cohort Study is a national longitudinal study applying a comprehensive model of research to understand the lived experience of individuals with spinal cord injury. Built on the framework of the International Classification of Functioning, Disability and Health and supported by an inclusive, multistakeholder governance structure, the Swiss Spinal Cord Injury Cohort Study enables biological, clinical, psychosocial, and policy-relevant research. This article presents its governance, delineates why the Swiss Spinal Cord Injury Cohort Study serves as a foundation for a learning health system, identifies emerging research needs in the context of the Swiss National SCI Strategy 2025-2034, and discusses key methodological challenges and opportunities of the Swiss Spinal Cord Injury Cohort Study. The Swiss Spinal Cord Injury Cohort Study represents a pioneering and sustainable model for data-driven, person-centered research, which has positioned itself as a cornerstone of evidence-based policy and practice in Switzerland to foster health, functioning and inclusion of persons with spinal cord injury. Its foundational role in shaping the Swiss National SCI Strategy 2025-2034-and its mandate to support its implementation, monitoring and evaluation-underscore its strategic value. Beyond its national impact, the Swiss Spinal Cord Injury Cohort Study showcases how longitudinal cohort studies can support comprehensive research that tackles aspects relevant to the lives of persons with chronic diseases.
Introduction Health literacy (HL) is defined as the ability to access, understand, evaluate and apply health-related information, which can influence individuals’ health outcomes. Blue-collar workers, who often have lower educational attainment and experience language barriers, are at increased risk of limited HL. This systematic review aims to assess the prevalence of limited HL among blue-collar workers to inform the development of appropriate interventions for its improvement.Methods and analysis The systematic review will assess the prevalence of limited HL among blue-collar workers. We will include all quantitative study designs using any instrument for measuring general HL. We will exclude studies that focus on specific types of HL and specific health conditions. We have performed a literature search from inception up to 30 April 2025, in the Medline, Embase, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) databases. We will also search eligible articles from Google Scholar and Open Grey as sources of unpublished studies/gray literature. Two independent reviewers will conduct the primary screening of articles, data extraction and quality assessment (using the Cochrane risk-of-bias tool for randomised trials and risk of bias in non-randomised studies of exposure), with a third individual available to resolve conflicts. We will assess heterogeneity using the χ² test and I² test. If there is sufficient homogeneity, we will pool studies in a meta-analysis or summarise the findings narratively if heterogeneity is too high. We will use a random effects model for our analysis, and we will use funnel plots to evaluate potential publication bias. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the certainty of findings.Ethics and dissemination Ethical approval will not be required for this review as there is no primary data collection involving humans. The results will be published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration number CRD42024597732.
This pilot study examined longitudinal changes in psychological distress and biomarkers related to stress, inflammation, and biological aging during the first inpatient rehabilitation after Spinal Cord Injury (SCI). We analyzed data from 120 participants in the SwiSCI inception cohort at two timepoints: the beginning of the first post-injury rehabilitation and discharge. A subset of 50 participants representing four distress patterns (high chronic, low, transient, increasing distress) underwent biomarker analyses, including measurements of immune and inflammatory proteins and whole-blood transcriptomic profiling. The results showed that psychological distress, depression, and protein carbonyl content decreased significantly by discharge. In contrast, cortisol levels and telomere length showed no significant changes. Proteomic analyses revealed a broad downregulation of inflammatory proteins (e.g., IFN-γ, IL-10, LIF) at discharge, whereas transcriptomic profiles did not differ between timepoints. The high chronic distress group showed lower expression of six genes involved in adaptive immunity, neural development and apoptosis. Psychological distress was not linearly associated with global biomarker profiles. However, CXCL1 and IL-7 showed low-to-moderate correlations with depression and anxiety, respectively. This pilot study demonstrates the feasibility of integrating psychological and molecular data to investigate biological response following SCI. The findings are exploratory and need validation in larger studies with longer follow-up periods.
INTRODUCTION:The length of stay (LOS) for inpatient SCI rehabilitation varies widely worldwide, including high-income countries. Understanding the individual factors that influence LOS at the country level provides valuable insights for optimizing rehabilitation services and resource allocation. Currently, representative data on LOS in rehabilitation following SCI in Switzerland are lacking. OBJECTIVE:To provide a population-based description of rehabilitation LOS and its determinants after SCI in Switzerland. METHODS:This study utilized data from the Swiss Spinal Cord Injury inception cohort, comprising individuals admitted to specialized rehabilitation between 2020 and 2023. Missingness was addressed using multiple imputation. Flexible parametric survival models were employed to identify significant relationships between rehabilitation LOS and the following determinants: patient and lesion characteristics, comorbidity status, functional independence at admission, common secondary health conditions (urinary tract infection, decubitus ulcers, and pneumonia), LOS in acute care, and rehospitalization. RESULTS:The main analysis included 831 individuals with SCI, revealing a median LOS of 139 days (IQR 79.0-189.0). Independent associations with rehabilitation LOS identified in the fully adjusted model included age at SCI, level and lesion severity, urinary tract infections, decubitus ulcers, and functional independence at admission. Additionally, pneumonia and rehospitalization were significantly associated with LOS in supplementary expanded analyses based on a larger sample size with increased power. CONCLUSION:This study described the LOS for SCI rehabilitation in Switzerland and identified critical patient- and lesion-related determinants. The insights gained are instrumental for healthcare providers and policymakers in enhancing the efficiency and quality of SCI rehabilitation services.
