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Objectives: Dementia is a clinical diagnosis without curative treatment. It is uncertain whether ancillary testing is beneficial for patients. This study investigates the association between use of diagnostic tests and time to poor outcome and health care costs., Design: Nationwide register-based cohort study using health care reimbursement data in the Netherlands., Setting and Participants: All Dutch hospitals, including 13,312 patients diagnosed with dementia in 2018., Methods: Diagnostic testing included computed tomography or magnetic resonance imaging (CT/MRI), neuropsychological examination (NPE), nuclear imaging (PET/SPECT), electroencephalography (EEG), and cerebrospinal fluid (CSF) testing. We compared time to poor outcome (institutionalization or death) and costs per month from 2018 to 2021 between those who underwent a specific diagnostic test in previous years to controls, propensity score matched for age, sex, type of hospital, and comorbidity., Results: Time to poor outcome in those who underwent CT/MRI, EEG, or CSF testing was similar to those who did not, but was longer for those who underwent NPE. Time to poor outcome was shorter in patients who underwent PET/SPECT. Patients who underwent CSF testing or PET/SPECT had higher mean total health care costs as compared to controls (CSF €248, 95% CI 64-433; PET/SPECT: €315, 95% CI 179-451). NPE during the diagnostic trajectory was associated with lower total health care cost (-€127, 95% CI -62, -193)., Conclusion and Implications: NPE was associated with longer time to poor outcome and lower health care costs, potentially due to confounding by indication. Patients who underwent neuroimaging (CT, MRI, SPECT/PET), CSF testing, or EEG for dementia diagnostics did not experience a longer time to poor outcome or lower health care costs. This emphasizes the importance of clinical examination as anchor for the diagnosis of dementia., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention., Methods: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed., Findings: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found., Interpretation: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up., Funding: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AW received research grants from EU IMI2 (MOPEAD), JPND (ADDITION, EURO-FINGER, PMI-AD), IHI (PROMINENT), and the Swedish VINNOVA program (PREDEM)(all paid to institution) and is licence holder of RUD-instrument (in part); outside the submitted work. RH received research grants from JPND, ZonMW, IMI, H2020 (paid to institution); received consulting fees from Lilly Nederland, iMTA, Biogen Nederlands, Biogen MA, Eisai (paid to institution); is a member of ISPOR special interest group open-source models, IPECAD modelling group and Alzheimer Europe Expert Advisory Panel (unpaid); outside the submitted work. SA received grants from EU (Institutional grant [Horizon 2020 Research and Innovation Programme agreement 779238]); Region Occitanie/Pyrénées-Méditerranée (1901175); the European Regional Development Fund (MP0022856); MSD Avenir Inspire Chairs of Excellence (Alzheimer Prevention in Occitania and Catalonia, EDENIS, KORIAN, Pfizer, and Pierre-Fabre); AXA Personal (current); Biogen Personal (2022); Roche Personal (2021); Leventis foundation (2022); ADI (2022); and has a leadership role in the French Alzheimer association (Scientific Committee); outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: There is increasing interest in the concept of frailty in stroke, including both physical frailty and imaging-evidence of brain frailty. We aimed to establish the prevalence of brain frailty in stroke survivors as well as the concurrent and predictive validity of various frailty measures against long-term cognitive outcomes., Methods: We included consecutively admitted stroke or transient ischaemic attack (TIA) survivors from participating stroke centres. Baseline CT scans were used to generate an overall brain frailty score for each participant. We measured frailty via the Rockwood frailty index, and a Fried frailty screening tool. Presence of major or minor neurocognitive disorder at 18-months following stroke or TIA was established via a multicomponent assessment. Prevalence of brain frailty was established based upon observed percentages within groups defined by frailty status (robust, pre-frail, frail). We assessed the concurrent validity of brain frailty and frailty scales via Spearman's rank correlation. We conducted multivariable logistic regression analyses, controlling for age, sex, baseline education and stroke severity, to evaluate association between each frailty measure and 18-month cognitive impairment., Results: Three-hundred-forty-one stroke survivors participated. Three-quarters of people who were frail had moderate-severe brain frailty and prevalence increased according to frailty status. Brain frailty was weakly correlated with Rockwood frailty (Rho: 0.336; p  < 0.001) and with Fried frailty (Rho: 0.230; p  < 0.001). Brain frailty (OR: 1.64, 95% CI = 1.17-2.32), Rockwood frailty (OR: 1.05, 95% CI = 1.02-1.08) and Fried frailty (OR: 1.93, 95% CI = 1.39-2.67) were each independently associated with cognitive impairment at 18 months following stroke., Conclusions: There appears to be value in the assessment of both physical and brain frailty in patients with ischaemic stroke and TIA. Both are associated with adverse cognitive outcomes and physical frailty remains important when assessing cognitive outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: 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., Objectives: To assess the effects of antithrombotic therapy for prevention of cognitive decline in people with small vessel disease on neuroimaging but without dementia., Search Methods: 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.  SELECTION CRITERIA: 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., Data Collection and Analysis: 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., Main Results: 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. 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. 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. 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). None of the included trials assessed the incidence of new dementia., Authors' Conclusions: 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., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: 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., Methods: 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., Results: 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)., Conclusions: 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., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objectives: Individuals with a low socioeconomic status (SES) have an increased risk of cardiovascular disease (CVD) and dementia, partly due to the high prevalence of unhealthy behaviours in this population. Interventions targeting lifestyle-related risk factors can potentially delay or prevent CVD and dementia onset. In this study, we explore the attitudes, experiences and views of low SES older adults on healthy lifestyles for the prevention of CVD and dementia. We also aim to study the potential role for coach-supported mobile health (mHealth) use, facilitating the development of the Prevention of Dementia using Mobile Phone Applications intervention., Design: We performed semi-structured interviews and used thematic analysis to analyse the data., Setting: Recruitment through multiple general practices in the Netherlands., Participants: Dutch non-demented adults aged ≥55, at increased risk of dementia, who possess a smartphone. Participants were purposively sampled on age, sex and history of CVD and diabetes., Results: Between May 2018 and June 2019, we performed 19 interviews. Five main themes were: (1) participants perceived little influence on their future health, (2) the sacrifices of healthy lifestyles outweighed the potential benefits, (3) physical complaints or disease could prompt behaviour change, (4) participants perceived they had limited self-efficacy to change their behaviour and (5) the social network had an important role in behaviour change. Needs regarding mHealth support were an easy-to-use smartphone application with trustworthy health information, which is provided in a non-obligatory way., Conclusions: Low SES older adults may benefit from lifestyle interventions that aim to improve self-efficacy levels by (remote) human support. Appropriateness and attractiveness of such interventions may increase when taking into account the participant's own autonomy, and when emphasising the direct gains of lifestyle changes for daily life. Moreover, involving the social network may be a valuable approach when developing lifestyle interventions for low SES older adults., Trial Registration Number: PRODEMOS trial, ISRCTN15986016; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) may be a promising technique to evaluate the presence of cerebral atherosclerosis. We tested whether the new and easily calculated ASL MRI parameter for vascular and tissue signal distribution - 'spatial coefficient of variation' (ASL-sCoV) - is a better radiological marker for atherosclerotic risk than the more conventional markers of white matter hyperintensity (WMH) volume and cerebral blood flow (ASL-CBF)., Methods: Participants of the preDIVA trial (n = 195), aged 72-80 years with systolic hypertension (>140 mmHg) underwent two MRI scans two to three years apart. WMH volume was derived from 3D FLAIR-MRI; gray matter ASL-CBF and ASL-sCoV from ASL-MRI. Atherosclerotic risk was operationalized as 10-year cardiovascular risk by the Systematic COronary Risk Evaluation Older Persons (SCORE O.P) and calculated at baseline and follow-up. Data were analyzed using linear regression., Results: ASL-CBF was associated with atherosclerotic risk scores at baseline (standardized-beta = -0.26, 95 %CI = -0.40 to -0.13, p < 0.001) but not at follow-up (standardized-beta = -0.14, 95 %CI = -0.33 to 0.04, p = 0.12). ASL-sCoV was associated with atherosclerotic risk scores at both time points (baseline standardized-beta = 0.23, 95 %CI = 0.10 to 0.36, p < 0.0001, follow-up standardized beta = 0.20, 95 %CI = 0.03 to 0.36, p = 0.02). WMH volume was not associated with atherosclerotic risk scores at either time-point. There were no longitudinal associations between changes in MRI parameters and baseline atherosclerotic risk scores., Conclusions: Our findings suggest that ASL-sCoV correlates better with atherosclerotic risk than the more conventional markers ASL-CBF and WMH volume. Our data reaffirm that non-invasive imaging with MRI is highly informative and could provide additional information about cerebrovascular damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China. Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China. Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities. Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes., Competing Interests: AG and MM were employed by Philips VitalHealth. LS and XY were employed by Fuzhou Comvee Network &Technology Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hafdi, Eggink, Hoevenaar-Blom, Witvliet, Andrieu, Barnes, Brayne, Brooks, Coley, Georges, van der Groep, van Marwijk, van der Meijden, Song, Song, Wang, Wang, Wang, Wimo, Ye, van Charante and Richard.)

Background and Purpose: The optimal management of post-stroke cognitive impairment (PSCI) 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 regarding prevention, diagnosis, treatment and prognosis., Methods: Guidelines were developed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations., Results: There was limited randomized controlled trial (RCT) evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Lifestyle interventions and treating vascular risk factors have many health benefits, but a cognitive effect is not proven. We found no evidence regarding routine cognitive screening following stroke, but recognize the importance of targeted cognitive assessment. We describe 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 cognition. The association between PSCI and acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on brain magnetic resonance imaging may help predict cognitive outcomes., Conclusions: These guidelines highlight fundamental areas where robust evidence is lacking. Further definitive RCTs are needed, and we suggest priority areas for future research., (© 2021 European Academy of Neurology and European Stroke Organisation.)