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Cognitive impairment is independently associated with kidney disease and increases in prevalence with declining kidney function. At the stage where kidney replacement therapy is required, with dialysis or transplantation, cognitive impairment is up to three times more common, and can present at a younger age. This is not a new phenomenon. The cognitive interactions of kidney disease are long recognized from historical accounts of uremic encephalopathy and so-called “dialysis dementia” to the more recent recognition of cognitive impairment in those undergoing kidney replacement therapy (KRT). The understanding of cognitive impairment as an extra-renal complication of kidney failure and effect of its treatments is a rapidly developing area of renal medicine. Multiple proposed mechanisms contribute to this burden. Advanced vascular aging, significant multi-morbidity, mood disorders, and sleep dysregulation are common in addition to the disease-specific effects of uremic toxins, chronic inflammation, and the effect of dialysis itself. The impact of cognitive impairment on people living with kidney disease is vast ranging from increased hospitalization and mortality to decreased quality of life and altered decision making. Assessment of cognition in patients attending for renal care could have benefits. However, in the context of a busy clinical service, a pragmatic approach to assessing cognitive function is necessary and requires consideration of the purpose of testing and resources available. Limited evidence exists to support treatments to mitigate the degree of cognitive impairment observed, but promising interventions include physical or cognitive exercise, alteration to the dialysis treatment and kidney transplantation. In this review we present the history of cognitive impairment in those with kidney failure, and the current understanding of the mechanisms, effects, and implications of impaired cognition. We provide a practical approach to clinical assessment and discuss evidence-supported treatments and future directions in this ever-expanding area which is pivotal to our patients' quality and quantity of life.

Background: Pain is a common problem after stroke and is associated with poor outcomes. There is no consensus on the optimal method of pain assessment in stroke. A review of the properties of tools should allow an evidence based approach to assessment. Objectives: We aimed to systematically review published data on pain assessment tools used in stroke, with particular focus on classical test properties of: validity, reliability, feasibility, responsiveness. Methods: We searched multiple, cross-disciplinary databases for studies evaluating properties of pain assessment tools used in stroke. We assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool. We used a modified harvest plot to visually represent psychometric properties across tests. Results: The search yielded 12 relevant articles, describing 10 different tools (n = 1,106 participants). There was substantial heterogeneity and an overall high risk of bias. The most commonly assessed property was validity (eight studies) and responsiveness the least (one study). There were no studies with a neuropathic or headache focus. Included tools were either scales or questionnaires. The most commonly assessed tool was the Faces Pain Scale (FPS) (6 studies). The limited number of papers precluded meaningful meta-analysis at level of pain assessment tool or pain syndrome. Even where common data were available across papers, results were conflicting e.g., two papers described FPS as feasible and two described the scale as having feasibility issues. Conclusion: Robust data on the properties of pain assessment tools for stroke are limited. Our review highlights specific areas where evidence is lacking and could guide further research to identify the best tool(s) for assessing post-stroke pain. Improving feasibility of assessment in stroke survivors should be a future research target. Systematic Review Registration Number: PROSPERO CRD42019160679 Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019160679.

1.1 Background Greater anticholinergic burden (ACB) increases the risk of mortality in older individuals, yet the strength of this association varies between studies. One possible explanation for this variance is the use of different approaches to quantify ACB. This systematic review (PROSPERO number CRD42019115918) assessed the prognostic utility of ACB-specific measures on mortality in older individuals. 1.2 Methods Multiple cross-disciplinary databases were searched from 2006-2018. Observational studies assessing the association between ACB and mortality utilizing ≥1 ACB measure, involving persons aged ≥65 years were included. Screening and data extraction were performed by two independent reviewers, with disagreements resolved by a third independent reviewer. Risk of bias and quality of evidence were assessed using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Meta-analysis was conducted where appropriate. 1.3 Results Of 19,224 titles, 20 articles describing 18 cohort studies involving 498,056 older individuals were eligible. Eight anticholinergic-specific measures were identified; the Anticholinergic Cognitive Burden Scale (ACBS, n=9) and Anticholinergic Risk scale (ARS, n=8) were most frequently reported. The evidence base was of poor quality, with moderate to high risk of bias. Meta-analysis showed increased mortality risk. 1.4 Conclusions There was a modest association between some ACB measures and mortality, with most evidence derived from the ACBS. Studies comparing different measures within the same population were lacking. Analysis was limited by poor generalizability between studies, specifically regarding heterogeneity in methodology and reporting, as well as high risk of bias for most studies in the evidence base.

Increasing evidence suggests a role for endothelial cell (EC) dysfunction in pathogenesis of cerebral small vessel disease. Commonly used medications including certain antihypertensives and statins have EC-stabilizing effects. We used individual patient data from completed acute stroke trials to assess whether prior exposure to EC-stabilizing medications was associated with lacunar stroke, using lacunar stroke as a clinical proxy for cerebral small vessel disease. Across 12,002 patients with relevant data, 2,855 (24%) had a lacunar stroke presentation. Univariable analyses suggested potential confounding from vascular diseases treated with EC-stabilizing medications. Initial multivariable logistic regression gave conflicting results when describing the independent association of exposure to EC-stabilizing medication and lacunar stroke in the complete population (O.R. 0.87, 95% C.I.: 0.77- 0.98) and limited to those taking any antihypertensive (O.R. 1.51, 95% C.I.: 1.21-1.88). Re-running the analyses including statins in the EC-stabilizing category suggested a beneficial effect of EC-stabilizing medication exposure on lacunar stroke incidence (O.R. 0.83, 95% C.I.: 0.73-0.93). These results align with recent pre-clinical data and would support interventional trials of EC-stabilizing medication for preventing cerebral small vessel disease. Our results also suggest that analyses of EC-stabilizing interventions need to adjust for potential endothelial effects of other co-prescribed medication.

Background Visual impairment affects up to 70% of stroke survivors. We designed an app (StrokeVision) to facilitate screening for common post stroke visual issues (acuity, visual fields, and visual inattention). We sought to describe the test time, feasibility, acceptability, and accuracy of our app-based digital visual assessments against (a) current methods used for bedside screening and (b) gold standard measures. Methods Patients were prospectively recruited from acute stroke settings. Index tests were app-based assessments of fields and inattention performed by a trained researcher. We compared against usual clinical screening practice of visual fields to confrontation, including inattention assessment (simultaneous stimuli). We also compared app to gold standard assessments of formal kinetic perimetry (Goldman or Octopus Visual Field Assessment); and pencil and paper-based tests of inattention (Albert’s, Star Cancelation, and Line Bisection). Results of inattention and field tests were adjudicated by a specialist Neuro-ophthalmologist. All assessors were masked to each other’s results. Participants and assessors graded acceptability using a bespoke scale that ranged from 0 (completely unacceptable) to 10 (perfect acceptability). Results Of 48 stroke survivors recruited, the complete battery of index and reference tests for fields was successfully completed in 45. Similar acceptability scores were observed for app-based [assessor median score 10 (IQR: 9–10); patient 9 (IQR: 8–10)] and traditional bedside testing [assessor 10 (IQR: 9–10); patient 10 (IQR: 9–10)]. Median test time was longer for app-based testing [combined time to completion of all digital tests 420 s (IQR: 390–588)] when compared with conventional bedside testing [70 s, (IQR: 40–70)], but shorter than gold standard testing [1,260 s, (IQR: 1005–1,620)]. Compared with gold standard assessments, usual screening practice demonstrated 79% sensitivity and 82% specificity for detection of a stroke-related field defect. This compares with 79% sensitivity and 88% specificity for StrokeVision digital assessment. Conclusion StrokeVision shows promise as a screening tool for visual complications in the acute phase of stroke. The app is at least as good as usual screening and offers other functionality that may make it attractive for use in acute stroke. Clinical Trial Registration https://ClinicalTrials.gov/ct2/show/NCT02539381.

A measure of treatment effect is needed to assess the utility of any novel intervention in acute stroke. For a potentially disabling condition such as stroke, outcomes of interest should include some measure of functional recovery. There are many functional outcome assessments that can be used after stroke. In this narrative review, we discuss exemplars of assessments that describe impairment, activity, participation, and quality of life. We will consider the psychometric properties of assessment scales in the context of stroke trials, focusing on validity, reliability, responsiveness, and feasibility. We will consider approaches to the analysis of functional outcome measures, including novel statistical approaches. Finally, we will discuss how advances in audiovisual and information technology could further improve outcome assessment in trials.