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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.)

Importance: High visit-to-visit blood pressure variability (BPV) in late life may reflect increased dementia risk better than mean systolic blood pressure (SBP). Evidence from midlife to late life could be crucial to understanding this association., Objective: To determine whether visit-to-visit BPV at different ages was differentially associated with lifetime incident dementia risk in community-dwelling individuals., Design, Setting, and Participants: This cohort study analyzed data from the Adult Changes in Thought (ACT) study, an ongoing population-based prospective cohort study in the US. Participants were 65 years or older at enrollment, community-dwelling, and without dementia. The study focused on a subset of deceased participants with brain autopsy data and whose midlife to late-life blood pressure data were obtained from Kaiser Permanente Washington medical archives and collected as part of the postmortem brain donation program. In the ACT study, participants underwent biennial medical assessments, including cognitive screening. Data were collected from 1994 (ACT study enrollment) through November 2019 (data set freeze). Data analysis was performed between March 2020 and September 2023., Exposures: Visit-by-visit BPV at ages 60, 70, 80, and 90 years, calculated using the coefficient of variation of year-by-year SBP measurements over the preceding 10 years., Main Outcomes and Measures: All-cause dementia, which was adjudicated by a multidisciplinary outcome adjudication committee., Results: A total of 820 participants (mean [SD] age at enrollment, 77.0 [6.7] years) were analyzed and included 476 females (58.0%). A mean (SD) of 28.4 (8.4) yearly SBP measurements were available over 31.5 (9.0) years. The mean (SD) follow-up time was 32.2 (9.1) years in 27 885 person-years from midlife to death. Of the participants, 372 (45.4%) developed dementia. The number of participants who were alive without dementia and had available data for analysis ranged from 280 of those aged 90 years to 702 of those aged 70 years. Higher BPV was not associated with higher lifetime dementia risk at age 60, 70, or 80 years. At age 90 years, BPV was associated with 35% higher dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.02-1.79). Meta-regression of HRs calculated separately for each age (60-90 years) indicated that associations of high BPV with higher dementia risk were present only at older ages, whereas the association of SBP with dementia gradually shifted direction linearly from being incrementally to inversely associated with older ages., Conclusions and Relevance: In this cohort study, high BPV indicated increased lifetime dementia risk in late life but not in midlife. This result suggests that high BPV may indicate increased dementia risk in older age but might be less viable as a midlife dementia prevention target.

Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. HIGHLIGHTS: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches. HIGHLIGHTS: Dementia risk reduction is a global public health priority Population-level approaches change societal conditions to make them less conducive to dementia's modifiable risk factors, and increase exposure to protective factors. Urgent development of population-level approaches is required to reduce the prevalence of, and inequalities in, dementia Action is required from researchers, governments and business, funders, public health professionals, and science communicators., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Use of angiotensin II (ATII)-stimulating antihypertensive medication (AHM), including angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs), has been associated with lower dementia risk. Previous studies had relatively short follow-up periods. The aim of this study is to investigate if these effects are sustained over longer periods., Methods: This post hoc observational analysis was based on data from a dementia prevention trial (preDIVA and its observational extension), among Dutch community-dwelling older adults without prior diagnosis of dementia. Differential associations between AHM classes and incident dementia were studied after 7.0 and 10.4 years, based on the median follow-up durations of dementia cases and all participants., Results: After 7 years, use of ATII-stimulating antihypertensives [hazard ratio = 0.68, 95% confidence interval (CI) = 0.47-1.00], ARBs (hazard ratio = 0.54, 95% CI = 0.31-0.94) and dihydropyridine CCBs (hazard ratio = 0.52, 95% CI = 0.30-0.91) was associated with lower dementia risk. After 10.4 years, associations for ATII-stimulating antihypertensives, ARBs and dihydropyridine CCBs attenuated (hazard ratio = 0.80, 95% CI = 0.61-1.04; hazard ratio = 0.75, 95% CI = 0.53-1.07; hazard ratio = 0.73, 95% CI = 0.51-1.04 respectively), but still suggested lower dementia risk when compared with use of other AHM classes. Results could not be explained by competing risk of mortality., Conclusion: Our results suggest that use of ARBs, dihydropyridine CCBs and ATII-stimulating antihypertensives is associated with lower dementia risk over a decade, although associations attenuate over time. Apart from methodological aspects, differential effects of antihypertensive medication classes on incident dementia may in part be temporary, or decrease with ageing., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study., Design: Qualitative semi-structured interview study, using thematic analysis., Setting: Primary and secondary care in Beijing and Tai'an, China., Participants: Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes., Results: We performed 26 interviews with participants aged 55-86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional., Conclusions: The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD., Trial Registration Number: 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.)

Purpose: Dementia and cardio-metabolic diseases share many risk factors. Management of these risk factors could contribute to successful aging, including the prevention of cardio-metabolic disease and dementia. The increasing use of smartphones offers an opportunity for remote preventive interventions. We provided a systematic review of telephone and smartphone-based interventions targeting the prevention of cognitive decline, dementia cardio-metabolic diseases or their risk factors among adults aged over 50 years., Patients and Methods: We searched Pubmed and the International Clinical Trials Registry Platform for experimental studies. We used the Cochrane risk-of-bias tool (Version 2) for randomized trials or TREND (Transparent Reporting of Evaluations with Nonrandomized Designs) checklists to assess study quality for completed studies., Results: We analyzed 21 completed (3 for cognition, 18 for cardio-metabolic outcomes) and 50 ongoing studies (23 for cognition, 27 for cardio-metabolic outcomes). Smartphone interventions were used in 26 studies (3 completed, 23 ongoing). Other interventions involved telephone vocal support and text messaging. Few studies were at low risk of bias. There were heterogeneous cognitive and cardio-metabolic outcomes. The highest quality studies found no significant effects on cognition, and inconsistent results for HbA1c, blood pressure or physical activity. The lower quality-studies found effects on global cognition, working memory, memory and language and inconsistent results for clinical, biological or behavioral cardio-metabolic outcomes., Conclusion and Implications: Despite the large number of commercially available mobile health applications, the magnitude of the scientific evidence base remains very limited. Based on published studies, the added value of telephone and smartphone tools for the prevention of cardio-metabolic diseases, cognitive decline or dementia is currently uncertain, but, there are several ongoing studies expected to be completed in the coming years., Competing Interests: Dr Sandrine Andrieu reports grants from CHU, Université Paul Sabatier, UMR1295, Toulouse, during the conduct of the study; personal fees from Roche, outside the submitted work. The authors declare no other conflicts of interest relevant to the current work., (© 2022 Andre et al.)

Background and Objectives: Low values of blood pressure, body mass index (BMI), and non-high-density lipoprotein (HDL) cholesterol have all been associated with increased dementia risk in late life, but whether these risk factors have an additive effect is unknown. This study assessed whether a combination of late-life low values for systolic blood pressure (SBP), BMI, and non-HDL cholesterol is associated with a higher dementia risk than individual low values of these risk factors., Methods: This is a post hoc analysis based on an observational extended follow-up of the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, including community-dwelling individuals, aged 70-78 years and free from dementia at baseline. We assessed the association of baseline low values of SBP, BMI, and non-HDL cholesterol with incident dementia using Cox regression analyses. First, we assessed the respective associations between quintiles of each risk factor and dementia. Second, we explored whether combinations of low values for cardiovascular risk factors increased dementia risk, adjusted for interaction and potential confounders., Results: During a median follow-up of 10.3 years (interquartile range 7.0-10.9 years), 308 of 2,789 participants (11.0%) developed dementia, and 793 (28.4%) died. For all risk factors, the lowest quintile was associated with the highest adjusted risk for dementia. Individuals with 1, 2, and 3 low values had adjusted HRs of 1.18 (95% CI 0.93-1.51), 1.28 (95% CI 0.85-1.93), and 4.02 (95% CI 2.04-7.93), respectively, compared with those without any low values. This effect was not driven by any specific combination of 2 risk factors and could not be explained by competing risk of death., Discussion: Older individuals with low values for SBP, BMI, or non-HDL cholesterol have a higher dementia risk compared with individuals without any low values. Dementia risk was substantially higher in individuals with low values for all 3 risk factors than expected based on a dose-response relationship. This suggests the presence of an overarching phenomenon that involves multiple risk factors simultaneously, rather than resulting from independent effects of each individual risk factor., Trial Registration Information: ISRCTN registry preDIVA: ISRCTN29711771. Date of study submission to ISRCTN registry: February 14, 2006. Recruitment start date: January 1, 2006. doi.org/10.1186/ISRCTN29711771., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be limitations in the existing nutrition clinical trials for dementia prevention. On the basis of this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic, and nutrition assessment tools, biomarkers, and novel clinical trial designs to guide future trial developments. Nutrition-based research has unique challenges that could require testing both more personalised interventions in targeted risk subgroups, identified by nutritional and other biomarkers, and large-scale and pragmatic study designs for more generalisable public health interventions across diverse populations.

Background: In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement can be an important part of the diagnostic evaluation. Typically clinical decision making about what to do next for a patient incorporates clinical judgement about the diagnosis with severity of symptoms and patient factors, such as their ideas and expectations for treatment. When evaluating patients for dementia, many GPs report using their own judgement to evaluate cognition, using information that is immediately available at the point of care, to decide whether someone has or does not have dementia, rather than more formal tests., Objectives: To determine the diagnostic accuracy of GPs' clinical judgement for diagnosing cognitive impairment and dementia in symptomatic people presenting to primary care. To investigate the heterogeneity of test accuracy in the included studies., Search Methods: We searched MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science Core Collection (ISI Web of Science), and LILACs (BIREME) on 16 September 2021., Selection Criteria: We selected cross-sectional and cohort studies from primary care where clinical judgement was determined by a GP either prospectively (after consulting with a patient who has presented to a specific encounter with the doctor) or retrospectively (based on knowledge of the patient and review of the medical notes, but not relating to a specific encounter with the patient). The target conditions were dementia and cognitive impairment (mild cognitive impairment and dementia) and we included studies with any appropriate reference standard such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification of Diseases (ICD), aetiological definitions, or expert clinical diagnosis., Data Collection and Analysis: Two review authors screened titles and abstracts for relevant articles and extracted data separately with differences resolved by consensus discussion. We used QUADAS-2 to evaluate the risk of bias and concerns about applicability in each study using anchoring statements. We performed meta-analysis using the bivariate method., Main Results: We identified 18,202 potentially relevant articles, of which 12,427 remained after de-duplication. We assessed 57 full-text articles and extracted data on 11 studies (17 papers), of which 10 studies had quantitative data. We included eight studies in the meta-analysis for the target condition dementia and four studies for the target condition cognitive impairment. Most studies were at low risk of bias as assessed with the QUADAS-2 tool, except for the flow and timing domain where four studies were at high risk of bias, and the reference standard domain where two studies were at high risk of bias. Most studies had low concern about applicability to the review question in all QUADAS-2 domains. Average age ranged from 73 years to 83 years (weighted average 77 years). The percentage of female participants in studies ranged from 47% to 100%. The percentage of people with a final diagnosis of dementia was between 2% and 56% across studies (a weighted average of 21%). For the target condition dementia, in individual studies sensitivity ranged from 34% to 91% and specificity ranged from 58% to 99%. In the meta-analysis for dementia as the target condition, in eight studies in which a total of 826 of 2790 participants had dementia, the summary diagnostic accuracy of clinical judgement of general practitioners was sensitivity 58% (95% confidence interval (CI) 43% to 72%), specificity 89% (95% CI 79% to 95%), positive likelihood ratio 5.3 (95% CI 2.4 to 8.2), and negative likelihood ratio 0.47 (95% CI 0.33 to 0.61). For the target condition cognitive impairment, in individual studies sensitivity ranged from 58% to 97% and specificity ranged from 40% to 88%. The summary diagnostic accuracy of clinical judgement of general practitioners in four studies in which a total of 594 of 1497 participants had cognitive impairment was sensitivity 84% (95% CI 60% to 95%), specificity 73% (95% CI 50% to 88%), positive likelihood ratio 3.1 (95% CI 1.4 to 4.7), and negative likelihood ratio 0.23 (95% CI 0.06 to 0.40). It was impossible to draw firm conclusions in the analysis of heterogeneity because there were small numbers of studies. For specificity we found the data were compatible with studies that used ICD-10, or applied retrospective judgement, had higher reported specificity compared to studies with DSM definitions or using prospective judgement. In contrast for sensitivity, we found studies that used a prospective index test may have had higher sensitivity than studies that used a retrospective index test., Authors' Conclusions: Clinical judgement of GPs is more specific than sensitive for the diagnosis of dementia. It would be necessary to use additional tests to confirm the diagnosis for either target condition, or to confirm the absence of the target conditions, but clinical judgement may inform the choice of further testing. Many people who a GP judges as having dementia will have the condition. People with false negative diagnoses are likely to have less severe disease and some could be identified by using more formal testing in people who GPs judge as not having dementia. Some false positives may require similar practical support to those with dementia, but some - such as some people with depression - may suffer delayed intervention for an alternative treatable pathology., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Digital health interventions could help to prevent age-related diseases, but little is known about how older adults engage with such interventions, especially in the long term, or whether engagement is associated with changes in clinical, behavioral, or biological outcomes in this population. Disparities in engagement levels with digital health interventions may exist among older people and be associated with health inequalities., Objective: This study aimed to describe older adults' engagement with an eHealth intervention, identify factors associated with engagement, and examine associations between engagement and changes in cardiovascular and dementia risk factors (blood pressure, cholesterol, BMI, physical activity, diet, and cardiovascular and dementia risk scores)., Methods: This was a secondary analysis of the 18-month randomized controlled Healthy Ageing Through Internet Counselling in the Elderly trial of a tailored internet-based intervention encouraging behavior changes, with remote support from a lifestyle coach, to reduce cardiovascular and cognitive decline risk in 2724 individuals aged ≥65 years, recruited offline in the Netherlands, Finland, and France. Engagement was assessed via log-in frequency, number of lifestyle goals set, measurements entered and messages sent to coaches, and percentage of education materials read. Clinical and biological data were collected during in-person visits at baseline and 18 months. Lifestyle data were self-reported on a web-based platform., Results: Of the 1389 intervention group participants, 1194 (85.96%) sent at least one message. They logged in a median of 29 times, and set a median of 1 goal. Higher engagement was associated with significantly greater improvement in biological and behavioral risk factors, with evidence of a dose-response effect. Compared with the control group, the adjusted mean difference (95% CI) in 18-month change in the primary outcome, a composite z-score comprising blood pressure, BMI, and cholesterol, was -0.08 (-0.12 to -0.03), -0.04 (-0.08 to 0.00), and 0.00 (-0.08 to 0.08) in the high, moderate, and low engagement groups, respectively. Low engagers showed no improvement in any outcome measures compared with the control group. Participants not using a computer regularly before the study engaged much less with the intervention than those using a computer up to 7 (adjusted odds ratio 5.39, 95% CI 2.66-10.95) or ≥7 hours per week (adjusted odds ratio 6.58, 95% CI 3.21-13.49). Those already working on or with short-term plans for lifestyle improvement at baseline, and with better cognition, engaged more., Conclusions: Greater engagement with an eHealth lifestyle intervention was associated with greater improvement in risk factors in older adults. However, those with limited computer experience, who tended to have a lower level of education, or who had poorer cognition engaged less. Additional support or forms of intervention delivery for such individuals could help minimize potential health inequalities associated with the use of digital health interventions in older people., (©Nicola Coley, Laurine Andre, Marieke P Hoevenaar-Blom, Tiia Ngandu, Cathrien Beishuizen, Mariagnese Barbera, Lennard van Wanrooij, Miia Kivipelto, Hilkka Soininen, Willem van Gool, Carol Brayne, Eric Moll van Charante, Edo Richard, Sandrine Andrieu, HATICE study group, PRODEMOS study group. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.05.2022.)

In old age, cognitive functions decline in comparison to performance earlier in life. Subjective memory complaints often cause anxiety. Patient and informant history taking, along with simple additional cognitive tests are usually sufficient to reassure patients or to initiate further diagnostic work-up. Differential diagnoses include depression, delirium, other psychiatric or neurological disorders, metabolic causes, intoxications or side effects of drugs. Physical examination and laboratory tests generally have limited added value. Main reasons for referral are a suspected treatable cause for cognitive decline (e.g. delirium), focal neurological deficit (e.g. stroke), suspected dementia under the age of 65-70 years, additional complex somatic or psychiatric disorders or further work-up in non-native speaking people.

Purpose: Cognitive diagnostic work-up in primary care is not always physically feasible, owing to chronic disabilities and/or travel restrictions. The identification of dementia might be facilitated with diagnostic instruments that are time efficient and easy to perform, as well as useful in the remote setting. We assessed whether the Telephone Interview for Cognitive Status (TICS) might be a simple and accurate alternative for remote diagnostic cognitive screening in primary care., Methods: We administered the TICS (range, 0-41) for 810 of 1,473 older people aged 84.5 (SD, 2.4) years. We scrutinized electronic health records for participants with TICS scores ≤30 and for a random sample of participants with TICS scores >30 for a dementia diagnosis using all data from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial for 8-12 years of follow-up. We used multiple imputation to correct for verification bias., Results: Of the 810 participants, 155 (19.1%) had a TICS score ≤30, and 655 (80.9%) had a TICS score >30. Electronic health records yielded 8.4% (13/154) dementia diagnoses for participants with TICS ≤30 vs none with TICS >30. Multiple imputation for TICS >30 yielded a median of 7/655 (1.1%; interquartile range, 5-8) estimated dementia cases. After multiple imputation, the optimal cutoff score was ≤29, with mean sensitivity 65.4%, specificity 87.8%, positive predictive value 11.9%, negative predictive value 99.0%, and area under the curve 77.4% (95% CI, 56.3%-90.0%)., Conclusions: In the present older population, the TICS performed well as a diagnostic screening instrument for excluding dementia and might be particularly useful when face-to-face diagnostic screening is not feasible in family practice or research settings. The potential reach to large numbers of people at low cost could contribute to more efficient medical management in primary care., (© 2022 Annals of Family Medicine, Inc.)

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.)

Importance: The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown., Objective: To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association., Design, Setting, and Participants: This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021., Exposures: Baseline systolic BP., Main Outcomes and Measures: All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines., Results: The study analyzed 7 cohort studies with a total of 17 286 participants, among whom 10 393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P = .001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P < .001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P = .03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P < .001) and 166 mm Hg (95% CI, 154-260 mm Hg; P = .02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct., Conclusions and Relevance: This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.

Competing Interests: We declare no competing interests.

Background: Older people with subjective memory complaints (SMC) and Instrumental Activities of Daily Living impairments (IADL-I) have an increased risk of developing dementia. Previous reports suggest that the predictive value of SMC and IADL-I may differ between sexes, leaving possible consequences for personalized risk prediction and prognosis. However, none of these studies addressed the competing risk of death, which may substantially differ between sexes., Objective: We investigated sex-differences in the association between IADL-I, SMC, and incident dementia and mortality as competing risk., Methods: 3,409 community-dwelling older people without dementia (mean age 74.3±2.5), were followed for 6.7 years (median). Baseline SMC were assessed using the 15-item Geriatric Depression Scale memory question, and IADL-I using the Academic Medical Center Linear Disability Score. Potential sex-differences in the predictive value of SMC and IADL-I were assessed using Cox regression models with an interaction term for sex., Results: HRs for isolated SMC and SMC + IADL-I and risk of dementia were higher in women (HR: 2.02, 95% CI = 0.91-4.46, p = 0.08; HR:2.85, 95% CI = 1.65-4.91, p < 0.001) than in men (HR:1.52, 95% CI = 0.86-2.69, p = 0.18; HR:1.24, 95% CI = 0.62-2.49, p = 0.54), but these sex-differences were not significant. Conversely, HRs for isolated IADL-I and risk of mortality were higher in men (HR:1.56, 95% CI = 1.18-2.05, p = 0.002) than in women (HR:1.14, 95% CI = 0.80-1.62, p = 0.48), but again, these sex-differences were not significant., Conclusion: The predictive value of SMC and IADL-I for the risk of dementia and mortality was not significantly modified by sex. However, the competing risk of death for these factors differed considerably between men and women, suggesting it is an essential factor to consider when comparing sex-differences in IADL/dementia risk.

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 <1 favour multi-domain interventions over control interventions. For incident dementia, there was no evidence of a difference between the multi-domain intervention group and the control group (RR 0.94, 95% CI 0.76 to 1.18; 2 studies; 7256 participants; high-certainty evidence). There was a small difference in composite Z-score for cognitive function measured with a neuropsychological test battery (NTB) (MD 0.03, 95% CI 0.01 to 0.06; 3 studies; 4617 participants; high-certainty evidence) and with the Montreal Cognitive Assessment (MoCA) scale (MD 0.76 point, 95% CI 0.05 to 1.46; 2 studies; 1554 participants), but the certainty of evidence for the MoCA was very low (due to serious risk of bias, inconsistency and indirectness) and there was no evidence of an effect on the MMSE (MD 0.02 point, 95% CI -0.06 to 0.09; 6 studies; 8697participants; moderate-certainty evidence). There was no evidence of an effect on mortality (RR 0.93, 95% CI 0.84 to 1.04; 4 studies; 11,487 participants; high-certainty evidence). There was high-certainty evidence for an interaction of the multi-domain intervention with ApoE4 status on the outcome of cognitive function measured with an NTB (carriers MD 0.14, 95% CI 0.04 to 0.25, noncarriers MD 0.04, 95% CI -0.02 to 0.10, P for interaction 0.09). There was no clear evidence for an interaction with baseline cognitive status (defined by MMSE-score) on cognitive function measured with an NTB (low baseline MMSE group MD 0.06, 95% CI 0.01 to 0.11, high baseline MMSE group MD 0.01, 95% CI -0.01 to 0.04, P for interaction 0.12), nor was there clear evidence for an effect in participants with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score > 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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: High blood pressure and blood pressure variability are potential, modifiable risk factors of poststroke dementia. We aimed to investigate the association between achieved blood pressure, blood pressure variability and poststroke dementia., Methods: We studied 17 064 patients with noncardioembolic ischemic stroke included in the Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) trial. We analysed the data as a single observational cohort. We studied mean achieved SBP and DBP and blood pressure variability defined as coefficient of variation (SD/mean∗100). The association between blood pressure and dementia was investigated with logistic regression analysis, correcting for sociodemographic factors and cardiovascular risk factors., Results: During 39 818 person-years of follow-up, 817 patients were diagnosed with dementia (2.1 per 100 person-years). We found a significant nonlinear association between mean SBP and the risk of dementia, implying a U-shaped association between mean SBP and dementia. Mean SBP of 120-129 mmHg was associated with a significantly higher risk of dementia than 130-139 mmHg [odds ratio (OR) 1.28; 95% confidence interval (95% CI) 1.03-1.58]. There was no indication of a U-shaped association between mean DBP and dementia, and no significant association between mean DBP categories and dementia. Higher blood pressure variability was associated with an increased risk of dementia (OR 1.06 per point increase, 95% CI 1.02-1.04), independent of mean SBP., Conclusion: Among patients with a recent noncardioembolic ischemic stroke, there appears to be a U-shaped association between achieved SBP and dementia. High blood pressure variability is associated with an increased risk of poststroke dementia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous estimates of the lifetime risk of dementia are restricted to older age groups and may suffer from selection bias. In this study, we estimated the lifetime risk of dementia starting at birth using nationwide integral linked health register data., Methods: We studied all deaths in The Netherlands in 2017 (n = 147 866). Dementia was assessed using the cause-of-death registration, individually linked with registers covering long-term care, specialized mental care, dispensed medicines, hospital discharges and claims, and primary care. The proportion of deaths with dementia was calculated for the total population and according to age at death and sex., Results: According to all data sources combined, 24.0% of the population dies in the presence of dementia. This proportion is higher for females (29.4%) than for males (18.3%). Using multiple causes of death only, the proportion with dementia is 17.9%. Sequential addition of long-term care and hospital discharge data increased the estimate by 4.0 and 1.5%-points, respectively. Further addition of dispensed medicines, hospital claims and specialized mental care data added another 0.6%-points. Among persons who die at age ≤65-70 years, the proportion with dementia is ≤6.2%. After age 70, the proportion rises sharply, with a peak of 43.9% for females and 33.1% for males at age 90-95 years., Conclusions: Around one-fourth of the Dutch population is diagnosed with dementia at some point in life and dies in the presence of dementia. It is a major challenge to arrange optimal care for this group., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: To systematically review and synthesize the evidence on differential associations between antihypertensive medication (AHM) classes and the risk of incident dementia., Design: Systematic review and random effects frequentist network meta-analysis. Embase, MEDLINE, and the Cochrane library were searched from origin to December 2019., Setting and Participants: Randomized controlled trials (RCTs) and prospective cohort studies that compared associations of different AHM classes with incident all-cause dementia and/or Alzheimer's disease over at least 1 year of follow-up., Measures: All cause dementia and/or Alzheimer's disease., Results: Fifteen observational studies and 7 RCTs were included. Data on AHM classes were available for 649,790 participants and dementia occurred in 19,600 (3.02%). Network meta-analysis showed that in observational studies, treatment with either calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs) was associated with lower dementia risks than treatment with other antihypertensives: CCBs vs angiotensin converting enzyme inhibitors (ACE inhibitors) (HR=0.84, 95% CI 0.74-0.95), beta blockers (HR=0.83, 95% CI 0.73-0.95) and diuretics (HR=0.89, 95% CI 0.78-1.01) and ARBs vs ACE inhibitors (HR=0.88, 95% CI 0.81-0.97), beta blockers (HR=0.87, 95% CI 0.77-0.99), and diuretics (HR=0.93, 95% CI 0.83-1.05). There were insufficient RCTs to create a robust network based on randomized data alone., Conclusions and Implications: Recommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia. If corroborated in a randomized setting, these findings reflect a low-cost and scalable opportunity to reduce dementia incidence worldwide., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Profiles 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 Analysis: The 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 Dissemination: The 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 Number: ISRCTN15986016., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis.", Methods: We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 ± 2.5) years., Results: After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease., Conclusions: Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Although not designed as such, dementia risk scores might be useful surrogate outcomes for dementia prevention trials. Their suitability may be improved by using continuous scoring systems, taking into account all changes in risk factors, not only those crossing cut-off values., Methods: In three large multidomain dementia prevention trials with 1.5 to 2 years of follow-up (Multidomain Alzheimer Preventive Trial, Prevention of Dementia by Intensive Vascular Care and Healthy Ageing Through Internet Counselling in the Elderly) we assessed (1) responsiveness (sensitivity to change) and (2) actual and simulated intervention effects of the original and crude/weighted z-score versions of the cardiovascular risk factors, aging and incidence of dementia, and Lifestyle for Brain Health scores., Results: All versions of the risk scores were generally responsive, and able to detect small though statistically significant between-group differences after multidomain interventions. Simulated intervention effects were well detected in z-score versions as well as in the original scores., Discussion: Dementia risk scores and their z-score versions show potential as surrogate outcomes. How changes in risk scores affect dementia remains to be determined., (© 2020 the Alzheimer's Association.)

Objectives: Prevention of cardiovascular disease (CVD) and dementia is a key health priority among older adults. Understanding individuals' attitudes to, the prevention of these conditions, particularly when delivered through novel eHealth tools, could help in designing effective prevention programmes. The aim of the study was to explore the attitudes of older adults at increased risk of CVD and dementia regarding engagement in eHealth self-management prevention programmes, and to describe the facilitators and barriers., Design: A qualitative research approach was used. Data were collected through eight focus groups in Finland, France and the Netherlands. Data were analysed following the principles of grounded theory., Setting and Participants: Forty-four community-dwellers aged 65+ at risk of CVD were recruited from a previous trial cohort in Finland, and through general practices in France and the Netherlands., Results: The study identified three categories: access to reliable information, trust in the healthcare providers and burden and stigma of dementia. A core category was also identified: the interactive process of the three categories influencing engagement in self-management prevention programme. The categories were interconnected through an interactive process and influenced by the local healthcare culture and context which shaped them differently, becoming either facilitators or barriers to engage in eHealth self-management prevention programmes., Conclusions: The study emphasises the importance of considering the interactions between the identified categories in this study, grounded in the local healthcare culture and context in further developments of eHealth self-management interventions that aim to prevent CVD and dementia., Trial Registration Number: ISRCTN48151589., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m 2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m 2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative., (© 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

An unhealthy lifestyle increases the risk of dementia. Two observational studies explored whether targeted health and lifestyle interventions could attenuate or even offset increased genetic risk. Results from these observational studies are inconclusive. However, after the age of 60, favourable lifestyle behaviours may have less impact in groups with high genetic risk. This might inspire researchers and clinicians to determine genetic risk prior to offering preventive interventions. However, this raises important ethical concerns and practical difficulties. Lifestyle interventions should take place irrespective of genetically determined risk of dementia.

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., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data., Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data., Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age., Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals., Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454., (© 2019 American Academy of Neurology.)

In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

A recent survey shows a steady growth in the number of memory clinics in the Netherlands over the last two decades. It appears there is considerable variation in both the organization of care and the type of diagnostic work-up that is provided. Over time, the memory clinic population has also changed; 22% of patients present with subjective memory complaints, a three-fold increase. Although the current dementia guidelines leave much room for individualized diagnostic trajectories, the results suggest a lack of consensus on the indication for the different diagnostic tests. More insight is needed in the causes of variation, before discussing to what extent this variation is acceptable or perhaps even desirable considering the widely differing patient populations. In the meantime, patients and carers deserve a more prominent role in the diagnostic process, to ensure that the quest for a timely diagnosis will go hand in hand with appropriate use of memory clinics.

Background: Studies on the association between depression and dementia risk mostly use sum scores on depression questionnaires to model symptomatology severity. Since individual items may contribute differently to this association, this approach has limited validity., Methods: We used network analysis to investigate the functioning of individual Geriatric Depression Scale (GDS-15) items, of which, based on studies that used factor analysis, 3 are generally considered to measure apathy (GDS-3A) and 12 depression (GDS-12D). Functional disability and future dementia were also included in our analysis. Data were extracted from 3229 participants of the Prevention of Dementia by Intensive Vascular care trial (preDIVA), analyzed as a single cohort, yielding 20,542 person-years of observation. We estimated a sparse network by only including connections between variables that could not be accounted for by variance in other variables. For this, we used a repeated L1 regularized regression procedure., Results: This procedure resulted in a selection of 59/136 possible connections. GDS-3A items were strongly connected to each other and with varying strength to several GDS-12D items. Functional disability was connected to all three GDS-3A items and the GDS-12D items "helplessness" and "worthlessness". Future dementia was only connected to the GDS-12D item "memory problems", which was in turn connected to the GDS-12D items "unhappiness" and "helplessness" and all three GDS-3A items., Conclusion: Network analysis reveals interesting relationships between GDS items, functional disability and dementia risk. We discuss what implications our results may have for (future) research on the associations between depression and/or apathy with dementia.

Purpose: Family physicians need simple yet comprehensive algorithms to discriminate between community-dwelling older persons who are at increased risk of dementia and those who are not. We aimed to investigate associations between incident dementia and responses to a single question regarding subjective memory complaints (SMC) combined with scores on 2 simple memory tests that are easy to use in the primary care setting., Methods: Analyses were based on data from 3,454 community-dwelling older persons who participated in the 6- to 8-year Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, yielding 21,341 person-years of observation. Participants were considered a single cohort. We used Cox models to assess separate and combined associations of SMC, an imperfect score on the Mini-Mental State Examination delayed recall item (MMSE-5), and an imperfect score on the Visual Association Test (VAT) with future dementia., Results: Subjective memory complaints alone were associated with future dementia (hazard ratio [HR] = 3.01; 95% CI, 2.31-3.94; P <.001), as were the MMSE-5 (HR = 2.14; 95% CI, 1.59-2.87; P <.001) and VAT (HR = 3.19; 95% CI, 2.46-4.13; P <.001) scores. After a median follow-up of 6.7 years, the occurrence of dementia ranged from 4% to 30% among persons with SMC, depending on the MMSE-5 and VAT scores. These test scores did not substantially alter the association with future dementia for persons without SMC., Conclusions: In persons with SMC, the strength of the association between future dementia and an imperfect MMSE-5 score depends substantially on the VAT score., (© 2019 Annals of Family Medicine, Inc.)

Objectives: To evaluate whether discontinuation of antihypertensive medication in community-dwelling older people is associated with a reduction in memory complaints and/or incident dementia., Design: Prospective observational cohort study within the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial., Setting and Participants: Community-dwelling participants (aged 70-78 years at baseline) who underwent 2-yearly assessments during 6-8 years of follow-up., Measures: Cox regression analyses of the relation between discontinuation of antihypertensive medication during the study and change in subjective memory complaints, incident dementia, and mortality., Results: Dementia occurred more often in participants discontinuing antihypertensive treatment (13.4% vs 6.2%, P = .02); mortality was similar (16.5% vs 13.9%, P = .52). Discontinuation of antihypertensive medication was associated with a double dementia hazard [hazard ratio (HR) (95% confidence interval) = 2.15 (1.15-4.03)], which somewhat attenuated after adjustment for sex, blood pressure, number of antihypertensives and other medications [HR = 1.92 (1.01-3.65)], and additionally for stroke, cardiovascular disease, diabetes, smoking, memory complaints, and MMSE score [HR = 1.79 (0.93-3.44)]. Antihypertensive discontinuation was associated with an approximately 50% higher hazard of dementia and/or mortality combined [HR = 1.58 (1.04-2.40); model 2: HR = 1.64 (1.07-2.51); model 3: HR = 1.49 (0.96-2.30)]. Antihypertensive discontinuation was not associated with change in memory complaints [odds ratio (95% confidence interval) = 0.96 (0.55-1.67)]. Subgroup and sensitivity analyses addressing possible sources of bias and confounding gave similar results., Conclusions/implications: Our results suggest that antihypertensive withdrawal in community-dwelling older people does not preserve cognition and may in fact increase dementia risk. This is not due to reduced mortality as competing risk. Additional analyses suggest results are unlikely to be explainable by confounding, reverse causality, or observational biases. Studies with person-specific reasons for antihypertensive discontinuation may be able to exclude reverse causality completely. Given the beneficial effects of antihypertensive medication on cardiovascular risk, observational data may be the best currently obtainable on the pressing issue of when withdrawal of antihypertensives in older people is acceptable and what consequences need to be weighed., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable., Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo., Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms., Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Early 2018 saw the release of new diagnostic guidance on Alzheimer's disease from the National Institute on Ageing and the Alzheimer's Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer's disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term 'Alzheimer's disease'; and the potential for a research framework to influence clinical practice., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies., Objective: To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia., Data Sources: Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases., Study Selection: Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia., Data Extraction and Synthesis: PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second., Main Outcomes and Measures: Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models., Results: The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1.32-2.50; I2 = 76%; n = 12), the hazard ratio was 2.39 (95% CI, 1.27-4.51; I2 = 90%; n = 7), and the odds ratio was 17.14 (95% CI, 1.91-154.0; I2 = 60%; n = 2). Subgroup analyses, meta-regression, and individual study results suggested the association between apathy and dementia weakened with increasing follow-up time, age, and cognitive impairment. Meta-regression adjusting for apathy definition and follow-up time explained 95% of heterogeneity in mild cognitive impairment., Conclusions and Relevance: Apathy was associated with an approximately 2-fold increased risk of dementia in memory clinic patients. Moderate publication bias may have inflated some of these estimates. Apathy deserves more attention as a relevant, cheap, noninvasive, and easily measureable marker of increased risk of incident dementia with high clinical relevance, particularly because these vulnerable patients may forgo health care.

Background: Selecting high-risk participants for dementia prevention trials based on a modifiable dementia risk score may be advantageous, as it increases the opportunity for intervention. We studied whether a multi-domain intervention can prevent all-cause dementia and cognitive decline in older people across three different levels of a modifiable dementia risk score., Methods: Prevention of Dementia by Intensive Vascular Care (preDIVA) is a randomised controlled trial studying the effect of multi-domain vascular care during 6-8 years on incident all-cause dementia in community-dwelling people aged 70-78 years. For this post hoc analysis, we stratified preDIVA participants in tertiles based on their baseline LIfestyle for BRAin Health (LIBRA) index, a modifiable dementia risk score. With Cox proportional hazards regression, the intervention effect on dementia was assessed. The effect on cognition was measured every 2 years with the Mini-Mental State Examination and Visual Association Test., Results: Dementia developed in 220 of 3274 (6.7%) participants. In participants with a low, intermediate and high LIBRA index, the hazard ratio (HR) of the intervention on incident dementia was respectively 0.71 (95% CI 0.45-1.12), 1.06 (95% CI 0.66-1.69) and 1.02 (95% CI 0.64-1.62). Also, when adding the non-modifiable risk factors age, education and sex to the index, results were comparable (respectively HR 0.88, 95% CI 0.54-1.43; HR 0.91, 95% CI 0.57-1.47; HR 0.92, 95% CI 0.59-1.41). There was no statistically significant intervention effect on cognition during follow-up across the LIBRA groups., Conclusions: In the preDIVA study population aged 70-78 years, the LIBRA modifiable dementia risk score did not identify a (high-)risk group in whom the multi-domain intervention was effective in preventing dementia or cognitive decline., Trial Registration: International Standard Randomised Controlled Trial Number registry, ISRCTN29711771 . Registered on 14 February 2006.

Purpose: The Mini-Mental State Examination (MMSE) is one of the most widely used instruments to screen for cognitive deficits; however, this instrument alone is not sensitive enough to detect early symptoms of dementia. We aimed to investigate whether additionally using the Visual Association Test (VAT) improves the predictive value of the MMSE score for development of dementia., Methods: Analyses were based on data from 2,690 primary care patients aged 70 to 78 years who participated in the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial. We assessed change in the 30-point MMSE score over 2 years and the VAT score at 2 years-dichotomized as perfect (6 points) or imperfect (≤5 points)-and evaluated the predictive values of these tests for a diagnosis of dementia in the subsequent 4 to 6 years. Data were analyzed with logistic regression analysis., Results: Patients having a decline of 2 points or more in total MMSE score over 2 years had an odds ratio of 3.55 (95% CI, 2.51-5.00) for developing dementia. Patients having the same decline in MMSE score plus an imperfect VAT score had an odds ratio of 9.55 (95% CI, 5.89-15.41) for developing dementia. A 1-point decline in MMSE score increased odds of dementia only when the VAT score was imperfect. Dementia risk for patients with a 2- or 3-point decrease in MMSE score and a perfect VAT score did not differ significantly from the average risk of the cohort as a whole., Conclusions: Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia. This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified., Competing Interests: Conflicts of interest: authors report none., (© 2018 Annals of Family Medicine, Inc.)

Objective: To assess whether apathy and depressive symptoms are independently associated with incident dementia during 6-year follow-up in a prospective observational population-based cohort study., Methods: Participants were community-dwelling older people in the Prevention of Dementia by Intensive Vascular Care trial, aged 70-78 years, without dementia at baseline. Apathy and depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Dementia during follow-up was established by clinical diagnosis confirmed by an independent outcome adjudication committee. Hazard ratios (HRs) were calculated using Cox regression analyses. Given its potentially strong relation with incipient dementia, the GDS item referring to memory complaints was assessed separately., Results: Dementia occurred in 232/3,427 (6.8%) participants. Apathy symptoms were associated with dementia (HR 1.28, 95% confidence interval [CI] 1.12-1.45; p < 0.001), also after adjustment for age, sex, Mini-Mental State Examination score, disability, and history of stroke or cardiovascular disease (HR 1.21, 95% CI 1.06-1.40; p = 0.007), and in participants without depressive symptoms (HR 1.26, 95% CI 1.06-1.49; p = 0.01). Depressive symptoms were associated with dementia (HR 1.12, 95% CI 1.05-1.19), also without apathy symptoms (HR 1.16, 95% CI 1.03-1.31; p = 0.015), but not after full adjustment or after removing the GDS item on memory complaints., Conclusions: Apathy and depressive symptoms are independently associated with incident dementia in community-dwelling older people. Subjective memory complaints may play an important role in the association between depressive symptoms and dementia. Our findings suggest apathy symptoms may be prodromal to dementia and might be used in general practice to identify individuals without cognitive impairment at increased risk of dementia., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: High visit-to-visit variability (VVV) in blood pressure (BP) is associated with cerebrovascular lesions on neuroimaging., Objective: Our primary objective was to investigate whether VVV is associated with incident all-cause dementia. As a secondary objective, we studied the association of VVV with cognitive decline and cardiovascular disease (CVD)., Methods: We included community-dwelling people (age 70-78 year) from the 'Prevention of Dementia by Intensive Vascular Care' (preDIVA) trial with three to five 2-yearly BP measurements during 6-8 years follow-up. VVV was defined using coefficient of variation (CV; SD/mean×100). Cognitive decline was assessed using the Mini-Mental State Examination (MMSE). Incident CVD was defined as myocardial infarction or stroke. We used a Cox proportional hazard regression and mixed-effects model adjusted for sociodemographic factors and cardiovascular risk factors., Results: In 2,305 participants (aged 74.2±2.5), mean systolic BP over all available visits was 150.1 mmHg (SD 13.6), yielding a CV of 9.0. After 6.4 years (SD 0.8) follow-up, 110 (4.8%) participants developed dementia and 140 (6.1%) CVD. Higher VVV was not associated with increased risk of dementia (hazard ratio [HR] 1.00 per point CV increase; 95% confidence interval [CI] 0.96-1.05), although the highest quartile of VVV was associated with stronger decline in MMSE (β -0.09, 95% CI -0.17 to -0.01). Higher VVV was associated with incident CVD (HR 1.07; 95% CI 1.04-1.11)., Conclusion: In our study among older people, high VVV is not associated with incident all-cause dementia. It is associated with decline in MMSE and incident CVD.

This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosis.

Objective: Use of antihypertensive medication (AHM) is potentially associated with a reduced risk of dementia. Both calcium channel blockers (CCBs) and angiotensin receptor blockers (ARBs) are suggested to have a more pronounced protective effect. We aimed to study the association between different classes of AHM and dementia in older people., Methods: A subgroup of community-dwelling older people using AHM included in the 'Prevention of Dementia by Intensive Vascular Care' randomized controlled trial was studied. Incident dementia rates in participants with different AHM classes (mono and combination therapy) were compared with dementia rates in participants with any other AHM., Results: At baseline, 1951 participants (55.3%) used AHM [mean age, 74.4 year (SD 2.5); mean SBP, 156.4 mmHg (SD 21.5)]. In total, 986 participants (50.5%) used β-blockers, 798 diuretics (40.9%), 623 angiotensin- converting enzyme inhibitors (31.9%), 522 CCBs (26.8%), and 402 ARBs (20.6%). After 6.7 years (interquartile range 6.0-7.3) of follow-up, 136 participants (7.0%) developed dementia. Both use of CCBs [hazard ratio 0.56, 95% confidence interval (95% CI) 0.36-0.87] and ARBs (hazard ratio 0.60, 95% CI 0.37-0.98) were independently associated with a decreased risk of dementia. The association of CCBs with dementia was most apparent in participants without a history of cardiovascular disease (hazard ratio 0.38, 95% CI 0.18-0.81) and with uncontrolled hypertension (hazard ratio 0.26, 95% CI 0.11-0.61). SBP was not significantly lower in participants using CCBs or ARBs., Conclusion: Both use of CCBs and ARBs are independently associated with a decreased risk of dementia in older people.

Objectives: To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years., Design: Secondary analysis., Setting: One hundred sixteen general practices in the Netherlands., Participants: Community-dwelling individuals aged 70 to 78 (N = 2,994)., Intervention: Nurse-led multidomain intervention targeting cardiovascular risk factors to prevent dementia., Measurements: The associations between participant baseline sociodemographic (age, sex, education), clinical (medical history, disability, cardiovascular risk), neuropsychiatric (depressive symptoms (Geriatric Depression Scale-15), and cognitive (Mini-Mental State Examination)) characteristics and dropout from the trial and nonadherence to the trial intervention were explored using multilevel logistic regression models., Results: Older age, poorer cognitive function, more symptoms of depression, and greater disability were the most important determinants of dropout of older people. The presence of cardiovascular risk factors was not associated with dropout but was associated with nonadherence. Being overweight was a risk factor for nonadherence, whereas people with high blood pressure or a low level of physical exercise adhered better to the intervention. The association between poorer cognitive function and symptoms of depression and dropout was stronger in the control group than in the intervention group, and vice versa for increased disability., Conclusion: In a large dementia prevention trial with 6-year follow-up, dropout was associated with older age, poorer cognitive function, symptoms of depression, and disability at baseline. These findings can help to guide the design of future dementia prevention trials in older adults. The associations found between cardiovascular risk factors and nonadherence need to be confirmed in other older populations receiving cardiovascular prevention interventions., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Background and Purpose: This study aimed to evaluate the effect of a nurse-led multidomain cardiovascular intervention on white matter hyperintensity (WMH) progression and incident lacunar infarcts in community-dwelling elderly with hypertension., Methods: The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. General practices were assigned by computer-generated randomization to 6-year nurse-led, multidomain intensive vascular care or standard care. Of 3526 preDIVA participants, 195 nondemented participants with a systolic blood pressure ≥140 mm Hg were consecutively recruited to undergo magnetic resonance imaging at 2 to 3 and 5 to 6 years after baseline. WMH volumes were measured automatically, lacunar infarcts assessed visually, blinded to treatment allocation., Results: One hundred and twenty-six participants were available for longitudinal analysis (64 intervention and 62 control). Annual WMH volume increase in milliliter was similar for intervention (mean=0.73, SD=0.84) and control (mean=0.70, SD=0.59) participants (adjusted mean difference, -0.08 mL; 95% confidence interval, -0.30 to 0.15; P =0.50). Analyses suggested greater intervention effects with increasing baseline WMH volumes ( P for interaction=0.03). New lacunar infarcts developed in 6 (9%) intervention and 2 (3%) control participants (odds ratio, 2.2; 95% confidence interval, 0.4-12.1; P =0.36)., Conclusions: Nurse-led vascular care in hypertensive community-dwelling older persons did not diminish WMH accumulation over 3 years. However, our results do suggest this type of intervention could be effective in persons with high WMH volumes. There was no effect on lacunar infarcts incidence but numbers were low., Clinical Trial Information: URL: http://www.isrctn.com/ISRCTN29711771. Unique identifier: ISRCTN29711771., (© 2017 American Heart Association, Inc.)

Background: Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands., Methods and Findings: A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data., Conclusions: Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come.