Is the difference real, is the difference relevant: the minimal detectable and clinically important changes in the Montreal Cognitive Assessment.

Background and aims: The Montreal Cognitive Assessment (MoCA) is a widely used instrument for assessing cognitive function in stroke survivors. To interpret changes in MoCA scores accurately, it is crucial to consider the minimal detectable change (MDC) and minimal clinically important difference (MCID). The aim was to establish the MDC and MCID of the MoCA within 6 months after stroke. Methods: This cohort study analysed data from the EFFECTS trial. The MoCA was administered at baseline and at 6-month follow-up. The MDC was calculated as the upper limit of the 95 % confidence interval of the standard error of the MoCA mean. The MCID was determined using anchor-based and distribution methods. The visual analogue recovery scale of the Stroke Impact Scale (SIS [primary anchor]) and Euro Quality of Life-5 Dimensions index (EQ-5D [confirmatory anchor]) were used as anchors. The distribution-based method, the Cohen benchmark effect size was chosen. Results: In total, 1131 (mean age [SD], 71 [10.6] years) participants were included. The mean (SD) MoCA scores at admission and 6-month follow-up were 22 (5.2) and 25 (4.2), respectively. The MDC of the MoCA was 5.1 points. The anchor method yielded the MCIDs 2 and 1.6 points for SIS and EQ-5D, respectively. Using the distribution method, the MCID for the MoCA was 1 point. Conclusions: Even a small change in MoCA scores can be important for stroke survivors; however, larger differences are required to ensure that any difference in MoCA values is a true change and is not related to the inherent variation in the test. Due to small sample sizes, the results of the anchor analysis need to be interpreted with caution.

Commentary on: physical activity and exercise for mild cognitive impairment and dementia: a collaborative international guideline.

Physical inactivity is an important, but potentially reversible risk factor for dementia and mild cognitive impairment (MCI). There is literature about physical activity and exercise for the prevention and management of dementia and MCI, but this had not been previously synthesized into specific guidelines about this topic. A recent guideline on physical activity and exercise in MCI and dementia was published, authored by several international societies, including lay representatives. In this commentary, we discuss the implications of this guidance for healthcare professionals, caregivers, and lay representatives involved in the care of people with MCI and dementia.The guidelines highlight the importance of physical activity and exercise in cognitively healthy persons and for dementia and MCI, at different stages of these conditions. For primary prevention of dementia, physical activity may be suggested in cognitively healthy persons. In people with MCI, mind-body interventions, such as yoga, have the greatest evidence, whilst the role of physical activity and exercise requires more evidence from high-quality randomized controlled trials. In people living with moderately severe dementia, exercise may be useful for maintaining physical and cognitive function. There are benefits of physical activity and exercise separate from their impact on cognitive outcomes. The guidelines also proposed some questions for future research. In conclusion, there is limited evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia. The guidelines support the promotion of physical activity based on the beneficial effects on almost all facets of health.

Validation of the brain health index in the European Prevention of Alzheimer's Dementia cohort.

Background: Brain Health Index (BHI) assimilates various MRI sequences, giving a quantitative measure of brain health. To date, BHI validation has been cross-sectional and limited to selected populations. Further large-scale validation and assessment of temporal change is required to understand its clinical utility. Aim: Assess 1) relationships between variables associated with cognitive decline and BHI 2) associations between BHI and measures of cognition and 3) longitudinal changes in BHI and relationship with cognitive function. Methods: BHI computation involved Gaussian mixture-model cluster analysis of T1, T2, T2*, and T2 FLAIR MRI data from participants within the European Prevention of Alzheimer's Dementia (EPAD) cohort. Group differences (gender- and health-based) were evaluated using independent samples Welch's t-tests. Relationships between BHI, age and cognitive tests used linear regression. Longitudinal analysis (12/24 months) utilised mixed linear regression models to examine BHI changes, and paired BHI/cognition associations. Results: Data from N = 1496 predominantly Caucasian participants (50-88 years old, 43.32% male) were used. BHI scores were lower in those with diabetes (p < 0.001, d = 0.419), hypertension (p < 0.001, d = 0.375), hypercholesterolemia (p < 0.001, d = 0.193) and stroke (p < 0.05, d = 0.512). APOE was not significantly related to BHI scores. After correction for age, cross-sectional BHI scores were significantly associated with all measures of cognitive function in males, but only the Four Mountains Test (4MT) in females. Longitudinal change in BHI and cognition were not consistently related. Conclusions: BHI is a valid marker of cognitive decline and relatively stable over 1-2 year follow-up periods. Further work should assess temporal changes over a longer duration and determine relationships between BHI and cognition in more diverse populations.

Clinical Phenotypes Associated With Cerebral Small Vessel Disease: An Overview of Systematic Reviews.

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (cSVD) causes lacunar and hemorrhagic stroke and is an important contributor to vascular cognitive impairment. Other potential physical and psychological consequences of cSVD have been described across various body systems. Descriptions of cSVD are available in journals specific to those individual body systems, but a comprehensive assessment of clinical manifestations across this disparate literature is lacking. We conducted an overview of systematic reviews describing clinical cSVD phenotypes. METHODS: We searched multidisciplinary databases from inception to December 2023. We included reviews describing concurrent clinical phenotypes in individuals with neuroimaging evidence of cSVD, defined using the STandards for ReportIng Vascular changes on nEuroimaging criteria. We broadly classified phenotypes into cognitive, mood and neuropsychiatric, respiratory, cardiovascular, renal-urinary, peripheral nervous system, locomotor, and gastrointestinal. We included both studies assessing multiple cSVD features and studies examining individual cSVD markers. We extracted risk factor-adjusted effect estimates, where possible, and assessed methodologic quality using the Assessment of Multiple Systematic Reviews-2 tool. RESULTS: After screening 6,156 publications, we included 24 systematic reviews reporting on 685 original studies and 1,135,943 participants. Cognitive and neuropsychiatric phenotypes were examined most often, particularly in relation to white matter hyperintensities (range of risk ratios [RRs] for cognitive phenotypes 1.21-1.49, range of 95% CI 1.01-1.84; for neuropsychiatric, RR 1.02-5.71, 95% CI 0.96-19.69). Two reviews focused solely on perivascular spaces. No reviews assessed lacunes or small subcortical infarcts separately from other cSVD features. Reviews on peripheral nervous system, urinary, or gastrointestinal phenotypes were lacking. Fourteen reviews had high methodologic quality, 5 had moderate quality, and 5 had low quality. Heterogeneity in cSVD definitions and phenotypic assessments was substantial. DISCUSSION: Neuroimaging markers of cSVD are associated with various clinical manifestations, suggesting a multisystem phenotype. However, features classically associated with cSVD, for example, gait, had limited supporting evidence, and for many body systems, there were no available reviews. Similarly, while white matter hyperintensities were relatively well studied, there were limited data on phenotypes associated with other cSVD features. Future studies should characterize the full clinical spectrum of cSVD and explore clinical associations beyond neurocognitive and neuropsychiatric presentations.

An automated flowchart for the Modified Rankin Scale assessment: A multicenter inter-rater agreement analysis.

BACKGROUND AND OBJECTIVE: The Modified Rankin Scale (mRS) is a widely adopted scale for assessing stroke recovery. Despite limitations, the mRS has been adopted as primary outcome in most recent clinical acute stroke trials. Designed to be used by multidisciplinary clinical staff, the congruency of this scale is not consistent, which may lead to mistakes in clinical or research application. We aimed to develop and validate an interactive and automated digital tool for assessing the mRS-the iRankin. METHODS: A panel of five board-certified and mRS-trained vascular neurologists developed an automated flowchart based on current mRS literature. Two international experts were consulted on content and provided feedback on the prototype platform. The platform contained five vignettes and five real video cases, representing mRS grades 0-5. For validation, we invited neurological staff from six comprehensive stroke centers to complete an online assessment. Participants were randomized into two equal groups usual practice versus iRankin. The participants were randomly allocated in pairs for the congruency analysis. Weighted kappa (kw) and proportions were used to describe agreement. RESULTS: A total of 59 professionals completed the assessment. The kw was dramatically improved among nurses, 0.76 (95% confidence interval (CI) = 0.55-0.97) × 0.30 (0.07-0.67), and among vascular neurologists, 0.87 (0.72-1) × 0.82 (0.66-0.98). In the accuracy analysis, after the standard mRS values for the vignettes and videos were determined by a panel of experts, and considering each correct answer as equivalent to 1 point on a scale of 0-15, it revealed a higher mean of 10.6 (±2.2) in the iRankin group and 8.2 (±2.3) points in the control group (p = 0.02). In an adjusted analysis, the iRankin adoption was independently associated with the score of congruencies between reported and standard scores (beta coefficient = 2.22, 95% CI = 0.64-3.81, p = 0.007). CONCLUSION: The iRankin adoption led to a substantial or near-perfect agreement in all analyzed professional categories. More trials are needed to generalize our findings. Our user-friendly and free platform is available at https://www.irankinscale.com/.

Imaging Biomarkers of VCI: A Focused Update.

Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.

Validation of general pain scores from multidomain assessment tools in stroke.

Purpose: We describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke. Materials and methods: Analyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain. Results: European Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0-10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0-10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0-10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = -0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0-10 NPRS. Discussion: The EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0-10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.

Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults.

CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. DESIGN: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). SETTING: Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS: In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSION: Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.

Seeing the forest (plot) for the trees-the importance of evidence synthesis in older adult care.

Systematically reviewing all the available evidence and then creating summary analyses of the pooled data is the foundation of evidence-based practice. Indeed, this evidence synthesis approach informs much of the care of older adults in hospital and community. It is perhaps no surprise that the journal Age and Ageing is a frequent platform for publishing research papers based on systematic review and synthesis. This research has evolved substantially from the early days of evidence-based medicine and the Cochrane Collaboration. The traditional approach would be a quantitative summary, calculated using pair-wise meta-analysis of randomised controlled trials of drug versus placebo, or a synthesis of observational studies to create summaries of prevalence, associations and outcomes. Methods have evolved and newer techniques such as scoping reviews, test accuracy meta-analysis and qualitative synthesis are all now available. The sophistication of these methods is driven in part by the increasingly complex decisions that need be made in contemporary older adult care. Age and Ageing continues to champion established and novel evidence synthesis approaches, and in the accompanying Collection exemplars of these differing methods are presented and described. Whilst there is marked heterogeneity in the techniques used, the consistent and defining feature of all these papers is the desire to comprehensively, and critically summarise the evidence in order to answer the most pertinent questions regarding older adult care.

Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR).

INTRODUCTION: Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research. METHODS AND ANALYSIS: We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials. TRIAL REGISTRATION NUMBER: NCT06108102.

Long-term psychological outcomes following stroke: the OX-CHRONIC study.

BACKGROUND: Stroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown. METHODS: N = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen's d effect size estimates and percent Minimal Clinically Important Difference changes between time points. RESULTS: On the Montreal Cognitive Assessment 65.3% scored < 26. On the Oxford Cognitive Screen 45.9% had at least one cognitive impairment. Attention (27.1%) and executive function (40%) were most frequently impaired. 23.5% and 22.5% had elevated depression/anxiety respectively. Fatigue (51.4%) and apathy (40.5%) rates remained high, comparable to estimates in the first-year post-stroke. Attention (d = -0.12; 85.8% stable) and depression (d = 0.09, 77.1% stable) were the most stable outcomes. Following alpha-adjustments, only perceptuomotor abilities (d = 0.69; 40.4% decline) and fatigue (d = -0.33; 45.3% decline) worsened over one year. Cognitive impairment, depression/anxiety, fatigue and apathy all correlated with worse quality of life. CONCLUSION: Nearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development.

New horizons in evidence synthesis for older adults.

Evidence synthesis, embedded within a systematic review of the literature, is a well-established approach for collating and combining all the relevant information on a particular research question. A robust synthesis can establish the evidence base, which underpins best practice guidance. Such endeavours are frequently used by policymakers and practitioners to inform their decision making. Traditionally, an evidence synthesis of interventions consisted of a meta-analysis of quantitative data comparing two treatment alternatives addressing a specific and focussed clinical question. However, as the methods in the field have evolved, especially in response to the increasingly complex healthcare questions, more advanced evidence synthesis techniques have been developed. These can deal with extended data structures considering more than two treatment alternatives (network meta-analysis) and complex multicomponent interventions. The array of questions capable of being answered has also increased with specific approaches being developed for different evidence types including diagnostic, prognostic and qualitative data. Furthermore, driven by a desire for increasingly up-to-date evidence summaries, living systematic reviews have emerged. All of these methods can potentially have a role in informing older adult healthcare decisions. The aim of this review is to increase awareness and uptake of the increasingly comprehensive array of newer synthesis methods available and highlight their utility for answering clinically relevant questions in the context of older adult research, giving examples of where such techniques have already been effectively applied within the field. Their strengths and limitations are discussed, and we suggest user-friendly software options to implement the methods described.

Prevalence, Trajectory, and Predictors of Poststroke Pain: Retrospective Analysis of Pooled Clinical Trial Data Set.

BACKGROUND: Poststroke pain remains underdiagnosed and inadequately managed. To inform the optimum time to initiate interventions, we examined prevalence, trajectory, and participant factors associated with poststroke pain. METHODS: Eligible studies from the VISTA (Virtual International Stroke Trials Archives) included an assessment of pain. Analyses of individual participant data examined demography, pain, mobility, independence, language, anxiety/depression, and vitality. Pain assessments were standardized to the European Quality of Life Scale (European Quality of Life 5 Dimensions 3 Level) pain domain, describing no, moderate, or extreme pain. We described pain prevalence, associations between participant characteristics, and pain using multivariable models. RESULTS: From 94 studies (n>48 000 individual participant data) in VISTA, 10 (n=10 002 individual participant data) included a pain assessment. Median age was 70.0 years (interquartile range [59.0-77.1]), 5560 (55.6%) were male, baseline stroke severity was National Institutes of Health Stroke Scale score 10 (interquartile range [7-15]). Reports of extreme pain ranged between 3% and 9.5% and were highest beyond 2 years poststroke (31/328 [9.5%]); pain trajectory varied by study. Poorer independence was significantly associated with presence of moderate or extreme pain (5 weeks-3 months odds ratio [OR], 1.5 [95% CI, 1.4-1.6]; 4-6 months OR, 1.7 [95% CI, 1.3-2.1]; >6 months OR, 1.5 [95% CI, 1.2-2.0]), and increased severity of pain (5 weeks-3 months: OR, 1.2 [95% CI, 1.1-1.2]; 4-6 months OR, 1.1 [95% CI, 1.1-1.2]; >6 months, OR, 1.2 [95% CI, 1.1-1.2]), after adjusting for covariates. Anxiety/depression and lower vitality were each associated with pain severity. CONCLUSIONS: Between 3% and 9.5% of participants reported extreme poststroke pain; the presence and severity of pain were independently associated with dependence at each time point. Future studies could determine whether and when interventions may reduce the prevalence and severity of poststroke pain.

Comparing Research Priority-Setting Partnerships for Older Adults Across International Health Care Systems: A Systematic Review.

OBJECTIVES: Priority setting partnerships (PSPs) attempt to shape the research agenda to address the needs of local populations of interest. We reviewed the PSPs for older adults, with a focus on exemplar health care systems: United Kingdom (UK; publicly funded), United States (private health insurance-based), South Korea (national health insurance-based), and Africa (out-of-pocket). DESIGN: Systematic review. SETTING AND PARTICIPANTS: We searched databases and sources (January 2011-October 202l; updated in February 2023) for PSPs of older adults' health care. METHODS: Based on the British geriatric medicine curriculum, we extracted and categorized the PSP topics by areas and the research priorities by themes, and generated evidence maps depicting and comparing the research gaps across the systems. We evaluated PSP quality using the Nine Common Themes of Good Clinical Practice. RESULTS: We included 32 PSPs (United Kingdom: n = 25; United States: n = 7; South Korea and Africa: n = 0) and identified priorities regarding 27 conditions or service arrangements in the United Kingdom and 9 in the United States (predominantly in neurology/psychiatry). The UK priorities focused on treatments and interventions whereas the US on prognostic/predictive factors. There were notable research gaps within the existing PSPs, including common geriatric conditions like continence and frailty. The PSP quality evaluation revealed issues around lacking inclusion of ethnic minorities. CONCLUSIONS AND IMPLICATIONS: Research priorities for older adult health care vary internationally, but certain health care systems/countries have no available PSPs. Where PSPs are available, fundamental aspects of geriatric medicine have not been included. Future researchers should conduct prioritizations in different countries, focus on core geriatric syndromes, and ensure the inclusion of all relevant stakeholder groups.