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Background: \ud Cerebral small vessel disease is a progressive disease of the brain's deep perforating blood vessels. It is usually diagnosed based on lesions seen on brain imaging. Cerebral small vessel disease is a common cause of stroke but can also cause a progressive cognitive decline. As antithrombotic therapy is an established treatment for stroke prevention, we sought to determine whether antithrombotic therapy might also be effective in preventing cognitive decline in people with small vessel disease.\ud \ud Objectives: \ud To assess the effects of antithrombotic therapy for prevention of cognitive decline in people with small vessel disease on neuroimaging but without dementia.\ud \ud Search methods: \ud We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Review Group's Specialised Register, and the Cochrane Stroke Group's Specialised Register; the most recent search was on 21 July 2021. We also searched MEDLINE, Embase, four other databases and two trials registries. We searched the reference lists of the articles retrieved from these searches. As trials with a stroke focus may include relevant subgroup data, we complemented these searches with a focussed search of all antithrombotic titles in the Cochrane Stroke Group database. \ud \ud Selection criteria: \ud We included randomised controlled trials (RCT) of people with neuroimaging evidence of at least mild cerebral small vessel disease (defined here as white matter hyperintensities, lacunes of presumed vascular origin and subcortical infarcts) but with no evidence of dementia. The trials had to compare antithrombotic therapy of minimum 24 weeks' duration to no antithrombotic therapy (either placebo or treatment as usual), or compare different antithrombotic treatment regimens. Antithrombotic therapy could include antiplatelet agents (as monotherapy or combination therapy), anticoagulants or a combination.\ud \ud Data collection and analysis: \ud Two review authors independently screened all the titles identified by the searches. We assessed full texts for eligibility for inclusion according to our prespecified selection criteria, extracted data to a proforma and assessed risk of bias using the Cochrane tool for RCTs. We evaluated the certainty of evidence using GRADE. Due to heterogeneity across included participants, interventions and outcomes of eligible trials, it was not possible to perform meta‐analyses.\ud \ud Main results: \ud We included three RCTs (3384 participants). One study investigated the effect of antithrombotic therapy in participants not yet on antithrombotic therapy; two studies investigated the effect of additional antithrombotic therapy, one in a population already taking a single antithrombotic agent and one in a mixed population (participants on an antithrombotic drug and antithrombotic‐naive participants). Intervention and follow‐up durations varied from 24 weeks to four years.\ud \ud Jia 2016 was a placebo‐controlled trial assessing 24 weeks of treatment with DL‐3‐n‐butylphthalide (a compound with multimodal actions, including a putative antiplatelet effect) in 280 Chinese participants with vascular cognitive impairment caused by subcortical ischaemic small vessel disease, but without dementia. There was very low‐certainty evidence for a small difference in cognitive test scores favouring treatment with DL‐3‐n‐butylphthalide, as measured by the 12‐item Alzheimer’s Disease Assessment Scale‐Cognitive subscale (adjusted mean difference −1.07, 95% confidence interval (CI) −2.02 to −0.12), but this difference may not be clinically relevant. There was also very low‐certainty evidence for greater proportional improvement measured with the Clinician Interview‐Based Impression of Change‐Plus Caregiver Input (57% with DL‐3‐n‐butylphthalide versus 42% with placebo; P = 0.01), but there was no difference in other measures of cognition (Mini‐Mental State Examination and Clinical Dementia Rating) or function. There was no evidence of a difference in adverse events between treatment groups.\ud \ud The SILENCE RCT compared antithrombotic therapy (aspirin) and placebo during four years of treatment in 83 participants with 'silent brain infarcts' who were on no prior antithrombotic therapy. There was very low‐certainty evidence for no difference between groups across various measures of cognition and function, rates of stroke or adverse events.\ud \ud The Secondary Prevention of Subcortical Stroke Study (SPS3) compared dual antiplatelet therapy (clopidogrel plus aspirin) to aspirin alone in 3020 participants with recent lacunar stroke. There was low‐certainty evidence of no effect on cognitive outcomes as measured by the Cognitive Abilities Screening Instruments (CASI) assessed annually over five years. There was also low‐certainty evidence of no difference in the annual incidence of mild cognitive decline between the two treatment groups (9.7% with dual antiplatelet therapy versus 9.9% with aspirin), or the annual stroke recurrence rate (2.5% with dual antiplatelet therapy versus 2.7% with aspirin). Bleeding risk may be higher with dual antiplatelet therapy (hazard ratio (HR) 2.15, 95% CI 1.49 to 3.11; low certainty evidence), but there may be no significant increase in intracerebral bleeding risk (HR 1.52, 95% CI 0.79 to 2.93; low‐certainty evidence).\ud \ud None of the included trials assessed the incidence of new dementia.\ud \ud Authors' conclusions: \ud We found no convincing evidence to suggest any clinically relevant cognitive benefit of using antithrombotic therapy in addition to standard treatment in people with cerebral small vessel disease but without dementia, but there may be an increased bleeding risk with this approach. There was marked heterogeneity across the trials and the certainty of the evidence was generally poor.

The optimal management of post-stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment and prognosis. These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post-stroke cognitive impairment and most acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on acute MRI brain may help predict cognitive outcomes. These guidelines have highlighted fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research. ispartof: European Stroke Journal vol:6 issue:3 pages:1-177 ispartof: location:England status: Published online

Various informant-based questionnaires are used in clinical practice to screen for pre-stroke cognitive problems. However, there is no guidance on which tool should be preferred. We compared the validity of the two most commonly used informant-based tools.We recruited consecutively admitted stroke patients. Patients' informants completed the Informant Questionnaire for Cognitive Decline in the Elderly Short Form (IQCODE-SF, 16-item) and Ascertain Dementia 8 (AD8). We assessed construct validity (accuracy) against a semi-structured clinical interview for dementia or mild cognitive impairment (MCI), describing test accuracy metrics and comparing area under ROC curves (AUROC). We described criterion validity by evaluating associations between test scores and neuroimaging markers of dementia and overall 'brain frailty'. Finally, we described prognostic validity comparing ROC curves for 18-month clinical outcomes of dementia, death, stroke, and disability.One-hundred-thirty-seven patient-informant dyads were recruited. At usual clinical cut-points, the IQCODE-SF had comparable sensitivity to the AD8 (both = 92%) for pre-stroke dementia, but superior specificity (IQCODE-SF: 82% vs. AD8: 58%). Youden index suggested that the optimal AD8 threshold for diagnosis of dementia is ≥4. The IQCODE-SF demonstrated stronger associations with markers of generalised and medial-temporal lobe atrophy, neurovascular disease, and overall brain frailty. IQCODE-SF also demonstrated greater accuracy for predicting future dementia (IQCODE-SF AUROC = 0.903, 95% CI = 0.798-1.00; AD8 AUROC = 0.821, 95% CI = 0.664-0.977).Both IQCODE-SF and AD8 are valid measures of pre-stroke dementia. Higher cut points for AD8 may improve performance in the acute stroke setting. Based on consistent superiority across a range of validity analyses, IQCODE-SF may be preferable to AD8 for pre-stroke dementia screening.

IntroductionProfiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%–40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.Methods and analysisThe prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness–implementation hybrid design, taking place in the UK and China. People are eligible if they are 55–75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.Ethics and disseminationThe PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London—Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People’s Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.Trial registration numberISRCTN15986016.

To determine variation in diagnostic strategies for diagnosing dementia between Dutch hospitals.Descriptive, retrospective research based on claim data of Dutch health insurers.Information on the use of diagnostic ancillary services carried out from 2015 to 2018 was collected via national-level insurance claims for patients who received a (new) diagnose-coding for dementia in 2018. Hospitals were included in the analysis if they diagnosed50 patients with dementia. We distinguished academic medical centres (AMC), non-academic training hospitals (TH) and general hospitals (GH).In 2018, 20.073 new cases of dementia were diagnosed in 71 hospitals. The percentages of patients undergoing MRI/CT-imaging ranged from 37 to 99% (median 76.7%), neuropsychological-assessment from 0-89% (median 31.8%), cerebrospinal fluid examination from 0-14% (median 2.4%), PET/SPECT-imaging from 0-16% (median 6.2%) and electroencephalography from 1-20% (median 5.8%). Practice variation was comparable in AMCs, THs and GHs and was evidently skewed for PET/SPECT-imaging, electroencephalography and cerebrospinal fluid examination. There were no distinct differences according to case-mix characteristics or hospital volume. The percentage of patients subjected to ancillary diagnostic investigations decreased sharply with increasing age.In the Netherlands, diagnostic ancillary methods used vary widely between hospitals both in frequency and modality. This variation may be driven by limited evidence of diagnostic accuracy and added value of different diagnostic tests, variations in doctor and patient preferences and differences in available diagnostic techniques per hospital. Further exploration of this heterogeneity may help to identify a strategy that combines the most benefit with the least burden.

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. Currently, no effective medical treatment exists to cure or to delay the onset of cognitive decline or dementia. Up to 40% of dementia is attributable to potentially modifiable risk factors, which has led to the notion that targeting these risk factors might reduce the incidence of cognitive decline and dementia. Since sporadic dementia is a multifactorial condition, thought to derive from multiple causes and risk factors, multi‐domain interventions may be more effective for the prevention of dementia than those targeting single risk factors. OBJECTIVES: To assess the effects of multi‐domain interventions for the prevention of cognitive decline and dementia in older adults, including both unselected populations and populations at increased risk of cognitive decline and dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), and ClinicalTrials.gov on 28 April 2021. We also reviewed citations of reference lists of included studies, landmark papers, and review papers to identify additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We defined a multi‐domain intervention as an intervention with more than one component, pharmacological or non‐pharmacological, but not consisting only of two or more drugs with the same therapeutic target. We included randomised controlled trials (RCTs) evaluating the effect of such an intervention on cognitive functioning and/or incident dementia. We accepted as control conditions any sham intervention or usual care, but not single‐domain interventions intended to reduce dementia risk. We required studies to have a minimum of 400 participants and an intervention and follow‐up duration of at least 12 months. DATA COLLECTION AND ANALYSIS: We initially screened search results using a ‘crowdsourcing’ method in which members of Cochrane’s citizen science platform identify RCTs. We screened the identified citations against inclusion criteria by two review authors working independently. At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence. We defined high‐certainty reviews as trials with a low risk of bias across all domains other than blinding of participants and personnel involved in administering the intervention (because lifestyle interventions are difficult to blind). Critical outcomes were incident dementia, incident mild cognitive impairment (MCI), cognitive decline measured with any validated measure, and mortality. Important outcomes included adverse events (e.g. cardiovascular events), quality of life, and activities of daily living (ADL). Where appropriate, we synthesised data in random‐effects meta‐analyses. We expressed treatment effects as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: We included nine RCTs (18.452 participants) in this review. Two studies reported incident dementia as an outcome; all nine studies reported a measure for cognitive functioning. Assessment of cognitive functioning was very heterogeneous across studies, ranging from complete neuropsychological assessments to short screening tests such as the mini‐mental state examination (MMSE). The duration of the interventions varied from 12 months to 10 years. We compared multi‐domain interventions against usual care or a sham intervention. Positive MDs and RRs 6 points (MD 0.07, 95%CI ‐0.00 to 0.15). AUTHORS' CONCLUSIONS: We found no evidence that multi‐domain interventions can prevent incident dementia based on two trials. There was a small improvement in cognitive function assessed by a NTB in the group of participants receiving a multi‐domain intervention, although this effect was strongest in trials offering cognitive training within the multi‐domain intervention, making it difficult to rule out a potential learning effect. Interventions were diverse in terms of their components and intensity.

Objectives To examine the association of benzodiazepines and anticholinergic drug usage with the risk of dementia. Design Prospective cohort study. Setting Community-dwelling participants, recruited in family practices in the Netherlands. Participants In total, 3526 individuals aged 70 to 78 years without dementia within 116 participating family practices. Methods Information about drug use was reported at baseline and at 2-year follow-up and was cross-checked with the participants’ electronic health records. Anticholinergic drug exposure was defined by the anticholinergic cognitive burden score. Participants were evaluated for dementia during follow-up assessments every 2 years, supplemented by information from electronic health records and the National Death Registry. Results During a median follow-up of 6.7 years, dementia developed in 233 participants (7%). In participants using benzodiazepines, 6% developed dementia vs 7% in nonusers [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58–1.07]. Persistent usage of benzodiazepines at baseline and after 2-year follow-up did not substantially alter the point-estimate (HR 0.60, 95% CI 0.34–1.10). Use of any anticholinergic drugs was not associated with incident dementia (HR 1.01, 95% CI 0.50–1.10). Dementia risk was significantly increased for participants with persistent drug use with a high anticholinergic cognitive burden score (HR 1.95, 95% CI 1.13–3.38) though this effect was absent when excluding participants taking antidepressants or antipsychotics (HR 0.42, 95% CI 0.06–3.01). Conclusions and Implications In our study population, benzodiazepine usage was not associated with an increased risk of dementia. Persistent high anticholinergic exposure was associated with an increased risk of dementia over 6 years of follow-up, and this association was driven by antidepressant or antipsychotic drug use, suggesting confounding by indication bias contributing to this. Although this observation could ameliorate prescription hesitance, healthcare providers are still advised to carefully weigh the potential benefits of benzodiazepines and anticholinergic drugs against the associated adverse health outcomes.