Parkwood Institute

Abstract Highlights We introduce the TMS-RAT, a reporting (assessment) tool for TMS studies Developed within a community-informed, iterative process rating 333 TMS studies Empirically evaluated for usability, inter-rater, and test-retest reliability A validated subset enables reliable retrospective assessment of reporting The modular structure enables use across a wide range of TMS study designs Background A standardised tool for comprehensive reporting can improve transparency, support consistent documentation, and enable comparison across transcranial magnetic stimulation (TMS) studies. The most used reporting checklist lacks clear definitions of full reporting and was not initially evaluated for usability or inter-rater reliability. A scoping review of studies using this checklist shows that its items are reported only 50% of the time, suggesting that method descriptions are often incomplete. Methods We developed the TMS Reporting Assessment Tool (TMS-RAT), a comprehensive reporting framework that provides clear definitions and examples for its items, covering a wide range of TMS protocols. We tested the usability and reliability of the TMS-RAT by rating all studies published between 1991 and 2025 using afferent conditioning (n = 333), a protocol encompassing many reporting categories identified during tool development. Seventeen independent raters contributed across three development phases, a validation phase, and a retest phase, with naïve raters introduced in each phase. Iterative refinements of the tool were informed by inter-rater reliability, qualitative rater feedback, and consultation with external TMS experts. Results We present two versions of the tool: the 72-item TMS-RAT v1.0, designed to guide comprehensive reporting, and the TMS-RAT v1.1, a subset of 50 items with the highest inter-rater (overall AC1 = 0.78, range = [0.60–0.99]) and test-retest reliability (overall AC1 = 0.82, range = [0.65–1.0]), intended for retrospective evaluation of reporting in systematic reviews, meta-analyses. Conclusion The TMS-RAT is a comprehensive, reliable tool that seeks to improve transparency and reproducibility in TMS research.

Introduction: Recent multidomain intervention trials for dementia show it is possible to improve cognition by targeting combinations of risk factors. We aimed to identify the most prevalent co-occurring risk factor combinations that are strongly associated with low cognition. Methods: This cross-sectional analysis included 30,097 participants aged 45 to 85 in the Canadian Longitudinal Study on Aging. The five most prevalent dyad, triad, and tetrad combinations of 12 modifiable risk factors were identified. Neuropsychological test battery composite Z score was calculated to assess cognition. Multivariable linear regression was used to explore the association between the prevalent combinations of risk factors and cognition. Synergistic interaction between risk factors was assessed using interaction terms. Results: The most prevalent dyadic combination was physical inactivity and sleep disturbance, with hypertension added for the triad, and obesity added for the tetrad. The dyadic combination associated with both high prevalence and the strongest association with low cognition was hearing loss and physical inactivity (prevalence 27%; mean difference −0.12 [95% CI: −0.14 to −0.09]). For the triad, it was hearing loss, physical inactivity, and hypertension (14%; −0.14 [−0.16 to −0.11]), and with the addition of obesity for the tetrad (5.1%; −0.15 [−0.19 to −0.12]). Synergistic interaction was observed between hypertension and physical inactivity (p < 0.001). Conclusion: Prevalent and detrimental combinations of modifiable risk factors for dementia were identified to inform targeted intervention strategies. The synergistic interaction between hypertension and physical inactivity highlights the benefit of addressing both risk factors simultaneously to maximize cognitive benefits.

Abstract INTRODUCTIONWe tested the hypothesis that increased middle cerebral artery velocity (MCA velocity) during complex motor (overground walking) and cognitive tasks (e.g., dual task) is associated with cognitive performance in older adults with varying levels of cognitive ability.METHODSFifty‐six participants (19 females, 75 ± 7 years old) completed a seated single task that assessed working memory performance; a walking single task, assessing overground walking gait speed; and a dual task, combining both. Continuous MCA velocity was collected, and participants completed a Montreal Cognitive Assessment (MoCA).RESULTSHigher MCA velocity was associated with faster gait speed, better working memory performance, and greater MoCA scores (all p &lt; 0.05). Participants with lower MoCA scores had lower MCA velocity (p = 0.052), slower gait speed (p = 0.035), and lower working memory performance (p = 0.016) than people with higher MoCA scores. The hyperemic response of MCA velocity from single task walking to the dual task with increased cognitive load significantly contributed to MoCA scores (p = 0.017).DISCUSSIONThe functional response of cerebral blood flow with these tests suggests vascular properties may be considered a biomarker indicative of subclinical cognitive function during walking tasks.Highlights Mobile devices simultaneously assessed neurovascular coupling and dual‐task cost. Middle cerebral artery velocity (MCA velocity) is negatively associated with dual‐task cost. MCA velocity is associated with gait speed, working memory, and Montreal Cognitive Assessment scores. MCA velocity decreased from controls to mild cognitive impairment to dementia. Novel methodological approach to utilize MCA velocity during overground walking, single‐tasks, and dual‐tasks.

BACKGROUNDDementia risk factors coexist and interact in meaningful ways. Identifying risk profiles can inform prevention strategies.METHODSThis study examined profiles using seven modifiable risk factors and their associations with cognition and sex among older adults at risk of dementia. Risk profiles were identified using principal component analysis, and linear regressions assessed their associations with cognition.RESULTSThree profiles emerged: (1) better sleep and social/psychological health; (2) better diet, physical activity, and vascular health; and (3) better cognitive engagement. Similar profiles were observed in women, except that better cognitive engagement grouped with poorer vascular health. In men, better cognitive engagement grouped with better vascular health and vision/hearing, while lower cognitive engagement was grouped with better sleep and social/psychological health. The lower cognitive engagement profile in men was associated with poorer cognition.DISCUSSIONPrevention strategies should target meaningful combinations of risk factors to improve dementia prevention. Further research is needed to validate and refine these profiles.HighlightsThis study evaluated risk profiles using a broad range of modifiable risk factors.This is the first study to analyze such profiles in a Canadian population, stratified by sex.Risk profiles differed by sex, especially for the cognitive engagement risk factor.In men, lower cognitive engagement profile was associated with poorer cognition.

ObjectiveRehabilitation is important for regaining mobility poststroke. Clinical practice guidelines suggest a high number of repetitive stepping activities to optimize subacute recovery especially when undertaken at intensities that challenge cardiovascular fitness. However, adherence to these guidelines is unclear. The objective of this study was to quantify aerobic minutes and step number in usual care inpatient stroke rehabilitation unit physical therapy sessions across Canada and identify characteristics of participants who met guideline aerobic intensity minutes at a session midpoint in their rehabilitation.MethodsTo gain insight into usual care, we analyzed cross-sectional data from the usual care arm of the Walk ‘n Watch implementation trial; trial sites included Canadian rehabilitation units that were not typically involved in research studies. To be included, medically stable patients were admitted for inpatient stroke rehabilitation, and able to take > 5 steps with a maximum of one person assisting. We assessed a midpoint physical therapy session with a wrist-based heart monitor (aerobic minutes) and ankle-based step counter (step number). Means, histograms, and correlations between aerobic minutes (> 40% heart rate reserve) and steps were calculated.ResultsThere were 166 participants (69 females, age 69 standard deviation (SD)12 years) with stroke (138 Ischemic/ 27 Hemorrhagic) included. Participants had a mean of 10(SD11) aerobic minutes and 985(SD579) steps. The relationship between step number and aerobic minutes was negligible (R2 = 0.003). More participants with ≥20 aerobic minutes in a session were male, with lower 6 Minute Walk Test distance, and have a subcortical stroke location.ConclusionThe number of steps has increased, but aerobic minutes has not changed and remains extremely low compared to published reports in the past several years. Given that increasing activity levels are critical for stroke recovery, further investigation into the potential barriers to achieving targets set by guidelines is recommended.Trial registrationClinicalTrials.gov NCT04238260

Carrying a variation in the gene for β-glucocerebrosidase is a major risk factor for Parkinson disease dementia (PDD), and raising β-glucocerebrosidase levels lowers α-synuclein in cell and animals. Ambroxol is a chaperone for β-glucocerebrosidase, which increases the levels of β-glucocerebrosidase. To examine the safety and tolerability of ambroxol in PDD, test the efficacy of ambroxol in improving or slowing the progression of cognitive deficits, and acquire pharmacological data. This was a 52-week, phase 2, double-blind, placebo-controlled, randomized clinical trial conducted from February 2015 to June 2023. The study took place at a single center and was referral based. Included were patients with PDD who were older than 50 years, had Parkinson disease for at least 1 year before cognitive impairment, had mild to moderate dementia, were taking stable medications, and had a study partner. Ambroxol low dose (525 mg per day), high dose (1050 mg per day), or placebo. Safety and tolerability outcomes were adverse events. Primary efficacy outcomes were the Alzheimer Disease Assessment Scale-cognitive subscale, version 13 (ADAS-Cog-13) and Clinician's Global Impression of Change (CGIC). A total of 75 patients were screened, and 55 were randomized. Thirty-one individuals received ambroxol, with 8 patients (mean [SD] age, 78.8 [3.4] years, all male) in the low-dose group and 22 patients (mean [SD] age, 70.7 [7.6]; 19 male [86.4%]) in the high-dose group. One patient was excluded from the high-dose group due to a diagnosis of progressive supranuclear palsy. A total of 24 patients (mean [SD] age, 72.7 [6.3] years; 19 male [79.2%]) were included in the placebo group. Participants receiving ambroxol (23 of 193 adverse events [12%]) showed more gastrointestinal adverse events than those receiving placebo (9 of 172 adverse events [5%]). Statistical analyses compared ambroxol high dose vs placebo. There was no evidence to suggest differences between groups on primary or secondary outcomes. Mean (SD) ambroxol high-dose concentrations were 7.48μM (3.17μM; 95% CI, 6.08-8.87μM) in plasma and 0.73μM (0.07μM; 95% CI, 0.64-0.81μM) in cerebrospinal fluid at the end of titration. Mean (SD) β-glucocerebrosidase levels were higher at week 26 (ambroxol, 12.45 [1.97] nmol/h/mg; 91% CI, 11.54-13.36 nmol/h/mg); placebo, 8.50 [1.96] nmol/h/mg; 91% CI, 7.65-9.34 nmol/h/mg; P = .05) in the ambroxol group compared with placebo. Results of this randomized clinical trial reveal that ambroxol was safe, well-tolerated, and demonstrated target engagement. However, the effect of ambroxol on cognition was not confirmed. ClinicalTrials.gov Identifier: NCT02914366.

Purpose This scoping review aims to explore the components of existing self-management interventions involving care partners of individuals with neurodegenerative movement disorders (NMDs). The review seeks to describe the key components, categorize different types and approaches using the PRISMS taxonomy. Methods A comprehensive search was conducted in five databases: SCOPUS, CINAHL, MEDLINE, PsycINFO, and Embase. Articles were included if they involved self-management interventions for adult care partners of individuals with NMDs. Data extraction was guided by the PRISMS, TEDSS and TIDieR frameworks, focusing on intervention characteristics, components, outcome measures, theories, and formats. Results The review included 34 articles, with most interventions targeting Parkinson’s Disease. Interventions varied widely in structure, delivery format, setting and content. Psychological and internal strategies were the most frequently utilized components. Notably, only 11 interventions were specifically designed for care partners. Conclusion This scoping review provides key insights into the diverse elements of self-management interventions for NMDs, including their structure, delivery format, and components. It highlights the lack of comprehensive dyadic interventions that support both individuals with NMDs and their care partners. Future research should explore the integration of personalization, communication training and dyadic coping strategies.

Cerebral lateralization of written language, much like oral language, is predominantly left lateralized. However, handwriting has been the primary focus in lateralization studies. The cerebral lateralization of typing-a widely used method of writing-remains unexamined. This preregistered study aimed to explore the cerebral lateralization of typing versus handwriting and to investigate possible handedness-related differences. We hypothesized that (i) cerebral lateralization would not differ between the two writing methods after movement correction and (ii) both handwriting and typing would show weaker lateralization in left-handers compared to right-handers. To investigate this, we used functional transcranial Doppler (fTCD) ultrasound, a reliable method for assessing cerebral lateralization during language tasks that remains unaffected by movement artifacts, such as those generated by handwriting and typing. A total of 24 left-handers and 30 right-handers participated, performing written word generation through both handwriting and typing on a computer keyboard while undergoing fTCD assessment. We applied a Bayesian framework for our analysis, as it enables us to demonstrate the absence of a difference (i.e., no difference between two variables), which is not possible with the use of p values (estimated under the frequentist framework). Our results provided evidence supporting the absence of a difference in cerebral lateralization between handwriting and typing after movement correction. However, we found no conclusive evidence to either support or refute a difference in lateralization between left-handers and right-handers, suggesting that more research is needed to clarify the role of handedness in cerebral lateralization for different writing methods.