Alzheimer's disease: From immunotherapy to immunoprevention.

Recent Aß-immunotherapy trials have yielded the first clear evidence that removing aggregated Aß from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising antibodies, optimize the timing of intervention, identify early biomarkers, and mitigate potential side effects.

Longitudinal Associations of Diet, Food Insecurity, and Supplemental Nutrition Assistance Program Use with Global Cognitive Performance in Middle-Aged and Older Adults.

BACKGROUND: Diet quality, food access, and food assistance policies may be key modifiable factors related to cognitive decline. OBJECTIVE: We aimed to evaluate whether diet quality, food insecurity, and Supplemental Nutrition Assistance Program (SNAP) use are associated with longitudinal changes in cognition among older adults in the United States. METHODS: Food intake data from the Health Care and Nutrition Study were linked with longitudinal health information from 5 waves of the Health and Retirement Study (2012-2020). The analytic sample (n = 6968) included community-dwelling United States adults aged ≥51 y without cognitive impairment. Global cognition was measured using a telephone-based cognitive status interview (range: 0-27). Diet quality was measured with the Healthy Eating Index, using participants' average intake of 13 dietary components. Questions regarding food access and affordability were used to determine food insecurity and use of SNAP benefits. Linear mixed-effects regression models were used to estimate longitudinal associations between diet-related factors and cognitive score changes. RESULTS: Poorer diets [ß: -0.24; 95% confidence interval (CI): -0.33, -0.15], food insecurity (ß: -1.08; 95% CI: -1.31, -0.85), and SNAP use (ß: -0.57; 95% CI: -0.82, -0.32) were associated with lower baseline cognitive scores. Poorer diets (ß: -0.17; 95% CI: -0.29, -0.05) and food insecurity (ß: -0.23; 95% CI: -0.47, -0.01) were associated with significantly steeper declines in cognitive scores over time, after 8 and 2 y of follow-up, respectively; however, SNAP use was not significantly associated with the rate of cognitive decline over time. Estimates were qualitatively similar when restricting the sample to participants aged ≥65 y. CONCLUSIONS: Results suggest that food access and adherence to healthy diet recommendations may be important elements to maintain cognitive health in aging. SNAP benefits may be insufficient to prevent negative cognitive effects of poor diet and limited access to nutritious foods.

Implementing the National Heart, Lung, and Blood Institute's Strategic Vision in the Division of Cardiovascular Sciences-2022 Update.

Spurred by the 2016 release of the National Heart, Lung, and Blood Institute's Strategic Vision, the Division of Cardiovascular Sciences developed its Strategic Vision Implementation Plan-a blueprint for reigniting the decline in cardiovascular disease (CVD) mortality rates, improving health equity, and accelerating translation of scientific discoveries into better cardiovascular health (CVH). The 6 scientific focus areas of the Strategic Vision Implementation Plan reflect the multifactorial nature of CVD and include (1) addressing social determinants of CVH and health inequities, (2) enhancing resilience, (3) promoting CVH and preventing CVD across the lifespan, (4) eliminating hypertension-related CVD, (5) reducing the burden of heart failure, and (6) preventing vascular dementia. This article presents an update of strategic vision implementation activities within Division of Cardiovascular Sciences. Overarching and cross-cutting themes include training the scientific workforce and engaging the extramural scientific community to stimulate transformative research in cardiovascular sciences. In partnership with other NIH Institutes, Federal agencies, industry, and the extramural research community, Division of Cardiovascular Sciences strategic vision implementation has stimulated development of numerous workshops and research funding opportunities. Strategic Vision Implementation Plan activities highlight innovative intervention modalities, interdisciplinary systems approaches to CVD reduction, a life course framework for CVH promotion and CVD prevention, and multi-pronged research strategies for combatting COVID-19. As new knowledge, technologies, and areas of scientific research emerge, Division of Cardiovascular Sciences will continue its thoughtful approach to strategic vision implementation, remaining poised to seize emerging opportunities and catalyze breakthroughs in cardiovascular sciences.

Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank.

OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta-analysis.

AIMS: The objective of this umbrella review and meta-analysis was to evaluate the effect of diabetes on risk of dementia, as well as the mitigating effect of antidiabetic treatments. MATERIALS AND METHODS: We conducted a systematic umbrella review on diabetes and its treatment, and a meta-analysis focusing on treatment. We searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and the Cochrane Library for systematic reviews and meta-analyses assessing the risk of cognitive decline/dementia in individuals with diabetes until 2 July 2023. We conducted random-effects meta-analyses to obtain risk ratios and 95% confidence intervals estimating the association of metformin, thiazolidinediones, pioglitazone, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, meglitinides, insulin, sulphonylureas, glucagon-like peptide-1 receptor agonists (GLP1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) with risk of dementia from cohort/case-control studies. The subgroups analysed included country and world region. Risk of bias was assessed with the AMSTAR tool and Newcastle-Ottawa Scale. RESULTS: We included 100 reviews and 27 cohort/case-control studies (N = 3 046 661). Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with significant reduction in risk of dementia. When studies examining metformin were divided by country, the only significant effect was for the United States. Moreover, the effect of metformin was significant in Western but not Eastern populations. No significant effect was observed for dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, or insulin, while meglitinides and sulphonylureas were associated with increased risk. CONCLUSIONS: Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with reduced risk of dementia. More longitudinal studies aimed at determining their relative benefit in different populations should be conducted.

Anti-amyloid antibody treatments for Alzheimer's disease.

Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-ß. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-ß is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-ß levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-ß yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease.

Impact of modifications to antidementia drug reimbursement in France: Analysis of the FRA-DEM cohort.

AIMS: Alzheimer's disease and related diseases (ADRD) is a progressive and inexorable disease. In France, acetylcholinesterase inhibitors and memantine were reimbursed for subjects with ADRD, until 2 modifications of their reimbursement rate (2012, 2018). We aimed to study the consequences of these measures on ADRD subjects' healthcare use. METHODS: We analysed data from the FRA-DEM cohort, including subjects with presumed incident ADRD identified since 2011 in the French health insurance system. We studied the healthcare use of subjects identified with incident ADRD in 2011, 2013, 2015, 2017 and 2019, notably the annual number of defined daily doses of various psychotropic groups. We performed 2 multivariate multinomial logistic regressions with the subcohort year as the dependent variable. RESULTS: In total, 165 120 subjects were included. A progressive decrease in exposure to antidementia drugs was observed between 2011 and 2019. Consultations with private neurologists or psychiatrists, and exposure to risperidone, antidepressants and benzodiazepines increased in the 2019 subcohort, following the 2018 reimbursement withdrawal. Meanwhile, the use of nursing/allied healthcare and emergency care increased over the subcohort years, whereas we observed a decrease in general practitioner consultations. CONCLUSION: These results suggest increases in private neurologist or psychiatrist consultations and exposure to recommended drugs after the reimbursement withdrawal, contrary to the fears expressed. However, antidementia drug exposure decreased long before the reimbursement modifications, probably due to the growing evidence of the modest effect of these drugs, and exposure to benzodiazepines increased after the reimbursement withdrawal.

The Effectiveness of the Case Manager-Centered Collaborative Care Model with Computer-Assisted Assessment on Quality Indicators for the Care of Dementia.

INTRODUCTION: This study aimed to investigate the influence of case management and its corresponding computer-assisted assessment system on the quality improvement of dementia care. METHODS: This observational study enrolled 2029 patients and their caregivers at Changhua Christian Hospital in Taiwan. Physicians who made the diagnosis of dementia would introduce the patient and caregiver dyad to the case manager-centered collaborative care team after obtaining agreement. The achievement rates of 11 quality indicators (QIs) comprising timely diagnostic evaluations, regular screens of cognition and neuropsychiatric symptoms, caregiver support, and proper medication prescriptions were counted. Different timeframes (≤4 months, 4 months-1 year, 1-2 years, 2-3 years, or ≥3 years) from diagnosis of dementia to collaborative care intervention were compared. RESULTS: A significantly higher attainment rate was achieved for patients with earlier entry into the collaborative team model, including QIs about timely diagnosis and regular screening, and caregiver support. The QIs regarding dementia medication prescriptions and documentation of the risk of antipsychotics remained similar regardless of the time of entry into the model. The completion rates of QIs also improved after the information system was launched. CONCLUSIONS: Physician-case manager co-management in the setting of a collaborative care model with a computer-assisted assessment system helps improve QI achievement for dementia care.

Increasing awareness for dementia risk reduction through a public awareness campaign in Denmark: A pre-post study.

OBJECTIVE: It is estimated that about 40% of all dementia cases are potentially attributable to modifiable risk factors, but awareness of this is relatively lacking. METHODS: An 18-months nation-wide public awareness campaign on dementia risk reduction was rolled out in Denmark that combined a mass-media approach with an online risk assessment tool and knowledge bank targeting all inhabitants aged between 40 and 75 years. Campaign effects (increase in awareness and knowledge of modifiable dementia risk and protective factors) were assessed via online surveys in two independent random samples before (n = 1003) and after the campaign (n = 1076). RESULTS: After adjusting for differences in educational level between the two samples, there was no significant difference in awareness of dementia risk reduction between the pre-campaign (66.5% aware) and post-campaign (63.4% aware) sample (probit z = -0.08, p = 0.151). The number of correctly identified risk/protective factors was significantly higher in the post-campaign sample. After adjusting for potential confounding factors, self-reported exposure to the campaign was associated with more awareness, better recognition of risk/protective factors, more motivation for and actual implementation of lifestyle changes. CONCLUSIONS: This mass-media campaign did not increase overall awareness that dementia risk is partly modifiable. However, exposure to the campaign was associated with more awareness and willingness to take action to improve brain health. Future campaigns should tailor messages to specific subgroups to broaden the reach (e.g., males), co-create materials with the target group, and give special attention to the contribution of metabolic/cardiovascular risk factors to dementia risk.

Robust reference group normative data for neuropsychological tests accounting for primary language use in Asian American older adults.

OBJECTIVE: The present study aimed to develop neuropsychological norms for older Asian Americans with English as a primary or secondary language, using data from the National Alzheimer's Coordinating Center (NACC). METHOD: A normative sample of Asian American participants was derived from the NACC database using robust criteria: participants were cognitively unimpaired at baseline (i.e., no MCI or dementia) and remained cognitively unimpaired at 1-year follow-up. Clinical and demographic characteristics were compared between Primary and Secondary English speakers using analyses of variance for continuous measures and chi-square tests for categorical variables. Linear regression models compared neuropsychological performance between the groups, adjusting for demographics (age, sex, and education). Regression models were developed for clinical application to compute demographically adjusted z-scores. RESULTS: Secondary English speakers were younger than Primary English speakers (p < .001). There were significant differences between the groups on measures of mental status (Mini-Mental State Examination, p = .002), attention (Trail Making Test A, Digit Span Forward Total Score, p <.001), language (Boston Naming Test, Animal Fluency, Vegetable Fluency, p < .001), and executive function (Trail Making Test B, p = .02). CONCLUSIONS: Separate normative data are needed for Primary vs. Secondary English speakers from Asian American backgrounds. We provide normative data on older Asian Americans to enable clinicians to account for English use in the interpretation of neuropsychological assessment scores.

Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis.

PURPOSE: We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. METHODS: We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID). RESULTS: We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86). CONCLUSIONS: Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.

The Rapid Access Memory Program for Addressing Concerns of Incipient Dementia in Academic Primary Care Settings.

BACKGROUND: Expedient diagnosis of incipient dementia is often hindered by time constraints in primary care visits, shortage of dementia specialists, and extended waitlists for comprehensive neuropsychological evaluations. METHODS: We developed the Rapid Access Memory Program (RAMP) to improve access of neuropsychological services for older adults presenting to our institutional primary care clinics with concerns of cognitive decline. RAMP provides abbreviated neurocognitive assessment, same-day patient feedback, expedited reporting to referring providers, and is financially self-supported. Here, we describe development of RAMP and clinical outcomes from the first 3 years. RESULTS: Of 160 patients seen, dementia was diagnosed in 30% and Mild Cognitive Impairment in 50%; Alzheimer's disease was the most common suspected etiology. New psychiatric diagnosis was made in about one-third (n = 54). Most frequent recommendations involved medication adjustments (initiating cholinesterase inhibitors, deprescribing anticholinergics), safety (driving, decision-making), and specialist referrals. Additionally, 27 (17%) subsequently enrolled in local research. CONCLUSIONS: Results support feasibility and utility of RAMP for connecting older adults in primary care with neuropsychological services.

Anti-amyloid antibody therapies in Alzheimer's disease.

After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-ß protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-ß lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors. Taken together, a real breakthrough may have been achieved by proving that amyloid-ß reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer's disease drug development.

Assessing the importance of primary care diagnoses in the UK Biobank.

The UK Biobank has made general practitioner (GP) data (censoring date 2016-2017) available for approximately 45% of the cohort, whilst hospital inpatient and death registry (referred to as "HES/Death") data are available cohort-wide through 2018-2022 depending on whether the data comes from England, Wales or Scotland. We assessed the importance of case ascertainment via different data sources in UKB for three diseases that are usually first diagnosed in primary care: Parkinson's disease (PD), type 2 diabetes (T2D), and all-cause dementia. Including GP data at least doubled the number of incident cases in the subset of the cohort with primary care data (e.g. from 619 to 1390 for dementia). Among the 786 dementia cases that were only captured in the GP data before the GP censoring date, only 421 (54%) were subsequently recorded in HES. Therefore, estimates of the absolute incidence or risk-stratified incidence are misleadingly low when based only on the HES/Death data. For incident cases present in both HES/Death and GP data during the full follow-up period (i.e. until the HES censoring date), the median time difference between an incident diagnosis of dementia being recorded in GP and HES/Death was 2.25 years (i.e. recorded 2.25 years earlier in the GP records). Similar lag periods were also observed for PD (median 2.31 years earlier) and T2D (median 2.82 years earlier). For participants with an incident GP diagnosis, only 65.6% of dementia cases, 69.0% of PD cases, and 58.5% of T2D cases had their diagnosis recorded in HES/Death within 7 years since GP diagnosis. The effect estimates (hazard ratios, HR) of established risk factors for the three health outcomes mostly remain in the same direction and with a similar strength of association when cases are ascertained either using HES only or further adding GP data. The confidence intervals of the HR became narrower when adding GP data, due to the increased statistical power from the additional cases. In conclusion, it is desirable to extend both the coverage and follow-up period of GP data to allow researchers to maximise case ascertainment of chronic health conditions in the UK.

Dementia care landscape in Nepal: Understanding the context, barriers, and opportunities for the development of a national dementia care plan.

OBJECTIVE: This study was conducted to comprehensively understand the context, barriers, and opportunities for improving dementia care, treatment, and support. The objective is to guide the development of a national dementia care plan. METHODOLOGY: This document review was conducted by analyzing literature available in the public domain, including scientific publications, project documents/reports, media reports, and hospital records. Additionally, annual reports published by the Department of Health Services, national census and demographic and health survey reports, Old Age Homes, and other relevant government reports were examined. Firsthand information was gathered from relevant stakeholders based on the World Health Organization's situational analysis framework for dementia plans. This framework encompasses four domains: Policy context (national ministries, legislation, policies, strategies, plans related to dementia, mental health, aging, and disability), service delivery assessment (health and social care workforces, services, support and treatment programmes, and promotion of awareness and understanding), and epidemiological indicators (prevalence and incidence rates of dementia, risk factors). Ethical clearance was obtained from the Institutional Review Committee (IRC) of B.P. Koirala Institute of Health Sciences (IRC no.2658/023). RESULTS: Existing policies in Nepal inadequately address the needs of people with dementia and their caregivers. Concerning health services, the Government of Nepal provides financial subsidies to individuals diagnosed with dementia; however, numerous hurdles impede access to care. These obstacles include geographical and structural barriers, an inefficient public healthcare system, weak governance, financial constraints, low awareness levels, stigma, and inadequate workforce. Furthermore, the absence of robust nationally representative epidemiological studies on dementia in Nepal hampers the development of evidence-based plans and policies. Similarly, there are no interventions targeted at caregivers of people with dementia, and no initiatives for dementia prevention are in place. CONCLUSIONS: This review underscores the urgent need to formulate a comprehensive national dementia care plan to address the growing challenges. Key priority action areas include the integration of dementia care into primary healthcare services, training workforce to provide the care, increasing awareness, mitigating stigma, developing caregiver support programs, and initiating high-quality research to inform evidence-based policymaking.

Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study.

BACKGROUND: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. SETTING: Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. METHODS: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). RESULTS: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. CONCLUSIONS: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.

Why to test for dementia: perspectives of patients, significant others and general practitioners.

BACKGROUND: This study aims to provide greater insight into the current decision-making process on diagnostic testing for dementia by exploring the expectations, needs and experiences of patients with memory complaints, significant others and general practitioners (GPs). METHODS: We performed semi-structured interviews with patients (>60 years) who consulted their GP on memory complaints, significant others and GPs. Participants were recruited until data saturation was reached in thematic analysis of interview transcripts. RESULTS: We performed 51 interviews (patients n = 20, significant others n = 15, GPs n = 16). Thematic analysis revealed four themes: (i) 'drivers to (not) testing', i.e. need to act on symptoms, beliefs on the necessity and expected outcomes of diagnostic testing; (ii) 'patient preferences and context are critical in the actual decision', i.e. in the actual decision-making process interpretation of symptoms, GPs' desire to meet patient preferences, social context and healthcare system dynamics guided the decision; (iii) 'need for individualised communication in the decision-making process', i.e. for patients feeling heard was a prerequisite for decision-making and GPs tailored communication strategies to individual patients and (iv) 'GP practice and barriers to shared decision-making (SDM)', i.e. although GPs value SDM in the decision on diagnostic testing for dementia, patients express limited awareness of the decision and options at stake. CONCLUSIONS: Decision-making on diagnostic testing for dementia is a multifactorial and preference-guided process for all involved stakeholders, but decisions are often not explicitly jointly made. Development of patient decision aids could facilitate better involvement and more informed choices by patients.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

Harnessing Speech-Derived Digital Biomarkers to Detect and Quantify Cognitive Decline Severity in Older Adults.

INTRODUCTION: Current cognitive assessments suffer from floor/ceiling and practice effects, poor psychometric performance in mild cases, and repeated assessment effects. This study explores the use of digital speech analysis as an alternative tool for determining cognitive impairment. The study specifically focuses on identifying the digital speech biomarkers associated with cognitive impairment and its severity. METHODS: We recruited older adults with varying cognitive health. Their speech data, recorded via a wearable microphone during the reading aloud of a standard passage, were processed to derive digital biomarkers such as timing, pitch, and loudness. Cohen's d effect size highlighted group differences, and correlations were drawn to the Montreal Cognitive Assessment (MoCA). A stepwise approach using a Random Forest model was implemented to distinguish cognitive states using speech data and predict MoCA scores based on highly correlated features. RESULTS: The study comprised 59 participants, with 36 demonstrating cognitive impairment and 23 serving as cognitively intact controls. Among all assessed parameters, similarity, as determined by Dynamic Time Warping (DTW), exhibited the most substantial positive correlation (rho = 0.529, p < 0.001), while timing parameters, specifically the ratio of extra words, revealed the strongest negative correlation (rho = -0.441, p < 0.001) with MoCA scores. Optimal discriminative performance was achieved with a combination of four speech parameters: total pause time, speech-to-pause ratio, similarity via DTW, and intelligibility via DTW. Precision and balanced accuracy scores were found to be 88.1 ± 1.2% and 76.3 ± 1.3%, respectively. DISCUSSION: Our research proposes that reading-derived speech data facilitates the differentiation between cognitively impaired individuals and cognitively intact, age-matched older adults. Specifically, parameters based on timing and similarity within speech data provide an effective gauge of cognitive impairment severity. These results suggest speech analysis as a viable digital biomarker for early detection and monitoring of cognitive impairment, offering novel approaches in dementia care.

Healthcare professionals' experiences and views of providing continence support and advice to people living at home with dementia: "That's a carer's job".

BACKGROUND: People living with dementia at home and their family carers often feel unsupported by healthcare professionals in managing continence problems. In turn, primary and community-based healthcare professionals have reported lacking specific knowledge on dementia-continence. This study aimed to understand more about healthcare professionals' experiences and views of supporting people living with dementia experiencing continence problems, as part of developing acceptable resources. Having a nuanced understanding of unmet need would facilitate the design of engaging resources that enable healthcare professionals to provide more effective continence support to people living with dementia at home. METHODS: Semi-structured interviews were conducted with a range of healthcare professionals (n = 31) working in primary and community care in the South of England in 2023. Transcribed interviews were uploaded to NVivo 12, then analysed inductively and deductively using a thematic framework. RESULTS: Continence-related conversations were avoided by many healthcare professionals due to lack of dementia-continence specific knowledge. Many considered that continence problems of people living with dementia were largely outside their remit once a physical cause had been ruled out. This contributed to a lack of priority and proactivity in raising the subject of continence in their consultations. Challenges to providing support included limited consultation time and lack of access to specialist services with availability to support individuals. CONCLUSION: There is substantial scope to support primary and community-based healthcare professionals in their provision of continence-related support and advice to people living at home with dementia. This includes addressing knowledge deficits, enhancing confidence and instilling a sense of accomplishment.