Healthcare professionals' perceptions of challenges in vaccine communication and training needs: a qualitative study.

BACKGROUND: Healthcare professionals (HCPs) can play an important role in encouraging patients and their caregivers to be vaccinated. The objective of this qualitative study was to investigate HCPs' perspectives on challenges in vaccine communication and unmet training needs in this domain. METHODS: Semi-structured interviews were conducted with 41 HCPs (mainly nurses and physicians) with vaccination roles (23 in England; 18 in France), gathering information on: (1) HCPs' approach to vaccine conversations with patients; (2) Challenges of communicating about vaccines; (3) Vaccine-related training and learning resources available to HCPs, and; (4) HCPs' training needs around vaccine communication. RESULTS: HCPs described a range of communication experiences that indicated insufficient time, information, and skills to confidently navigate difficult conversations with vaccine-hesitant patients. Communication skills were especially important to avoid conflict that could potentially damage the patient-provider relationship. Some HCPs interviewed had received communication training, but for most, this training was not specific to vaccination. Although general communication skills were transferable to vaccine conversations, most HCPs welcomed specific training and informational resources to support countering patients' misconceptions or misinformation about vaccines. CONCLUSIONS: HCPs would benefit from training tailored to address vaccine communication with patients, and this should be part of a systemic approach that also provides time and space to have effective vaccine conversations.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

Genetics impact risk of Alzheimer's disease through mechanisms modulating structural brain morphology in late life.

BACKGROUND: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively. METHODS: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants. RESULTS: Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk. CONCLUSIONS: Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.

Waiting to start abortion: A qualitative exploration of narratives of waiting shared in a Reddit community for abortion post-Dobbs leak in 2022.

With the Dobbs leak introducing uncertainty about access and the Dobbs v. Jackson Women's Health Organization decision in June of 2022 overturning the US constitutional right to abortion, delays in accessing desired abortion care are likely growing longer and more common. Timely research on people's experiences waiting to access abortion care is needed. Using data from an abortion subreddit (r/abortion), we analyzed posts that described waiting after having decided to terminate the pregnancy, either by having an in-clinic appointment or ordering medication(s) online for self-managed abortion. Our analysis explored described 1) wait time length, 2) factors contributing to waiting, and 3) impacts of waiting. We used a hybrid inductive and deductive thematic qualitative coding approach to analyze a month-stratified 10% random sample of posts to the r/abortion community in 2022 surrounding the Dobbs leak and decision (May-December, n = 523 posts). Among posts to r/abortion that described waiting to start an abortion (n = 80), wait times ranged from one day to more than a month. Lack of appointment availability and waiting for mailed medications were commonly described as causing delays in accessing in-clinic abortion care and self-managed abortion, respectively. People shared challenges with pregnancy symptoms and feelings of anxiety, fear, isolation, and uncertainty. Posters also commonly described needing additional support while waiting. Overall, waiting to start an abortion was extremely stressful and isolating., with people often waiting weeks between ordering medication or scheduling an appointment and initiating the abortion process. Experiences of waiting to start an abortion and their impacts are of increasing concern as abortion access is further restricted. Additional targeted information and support are needed to mitigate these challenges. Providing timely access is imperative to quality care and overall abortion experiences.

Determinants of Vaccine Hesitancy among African American and Black Individuals in the United States of America: A Systematic Literature Review.

Despite the crucial role the COVID-19 vaccine played in curbing the pandemic, a significant portion of Black and African American individuals expressed hesitancy toward being vaccinated. This review aimed to identify the determinants of COVID-19 vaccine hesitancy among Black and African American individuals in the U.S. The literature search was conducted in December 2022 according to the PRISMA criteria focusing on empirical studies. Data extraction methods, critical appraisal, and secondary thematic analysis were conducted on both quantitative and qualitative studies. Sixteen quantitative studies identified the key factors associated with vaccine hesitancy, such as confidence in vaccine effectiveness, safety, and trust in the healthcare system. Fourteen qualitative studies revealed major themes of mistrust, fear, and information needs, including historical mistrust, concerns about the vaccine development process, and contemporary institutional mistrust. The synthesis of quantitative and qualitative findings derived from this review provides a nuanced understanding of the determinants of vaccine hesitancy in Black and African American communities in the U.S., offering a foundation for the development of evidence-based interventions. Mistrust in the healthcare system, fear, and informational gaps on vaccine safety and effectiveness were identified as significant barriers to vaccination, demanding targeted interventions.

How Do Past Immunization Strategies Compare With the COVID-19 Immunization Rollout: A New Zealand Analysis.

OBJECTIVE: The aim of this study was to compare past New Zealand immunization strategies with the New Zealand coronavirus disease 2019 (COVID-19) immunization roll-out. METHODS: Using the READ document analysis method, 2 New Zealand immunization strategies (for influenza and measles) were analyzed for how the disease, context, vaccine supply and demand, ethical principles (equity, individual autonomy, and maximizing benefits), and the Treaty of Waitangi impacted the immunization programs. The findings were compared with the ongoing COVID-19 mass immunization program in New Zealand, as of October 15, 2021. RESULTS: Several themes common to the case-studies and the COVID-19 pandemic were identified including the importance of equity, obligations under the Treaty of Waitangi, ethical mandates, and preparedness. CONCLUSIONS: Future emergency planning should integrate learnings from other infectious disease responses and immunization programs to avoid repeating mistakes and to create better health outcomes. This study has provided a basis for ongoing research into how an appropriate immunization plan can be developed that incorporates ethical values, the Treaty of Waitangi (in the NZ context), and evidence-based research to increase trust, equity, health, and preparedness for future outbreaks.

Life course plasma metabolomic signatures of genetic liability to Alzheimer's disease.

Mechanisms through which most known Alzheimer's disease (AD) loci operate to increase AD risk remain unclear. Although Apolipoprotein E (APOE) is known to regulate lipid homeostasis, the effects of broader AD genetic liability on non-lipid metabolites remain unknown, and the earliest ages at which metabolic perturbations occur and how these change over time are yet to be elucidated. We examined the effects of AD genetic liability on the plasma metabolome across the life course. Using a reverse Mendelian randomization framework in two population-based cohorts [Avon Longitudinal Study of Parents and Children (ALSPAC, n = 5648) and UK Biobank (n ≤ 118,466)], we estimated the effects of genetic liability to AD on 229 plasma metabolites, at seven different life stages, spanning 8 to 73 years. We also compared the specific effects of APOE ε4 and APOE ε2 carriage on metabolites. In ALSPAC, AD genetic liability demonstrated the strongest positive associations with cholesterol-related traits, with similar magnitudes of association observed across all age groups including in childhood. In UK Biobank, the effect of AD liability on several lipid traits decreased with age. Fatty acid metabolites demonstrated positive associations with AD liability in both cohorts, though with smaller magnitudes than lipid traits. Sensitivity analyses indicated that observed effects are largely driven by the strongest AD instrument, APOE, with many contrasting effects observed on lipids and fatty acids for both ε4 and ε2 carriage. Our findings indicate pronounced effects of the ε4 and ε2 genetic variants on both pro- and anti-atherogenic lipid traits and sphingomyelins, which begin in childhood and either persist into later life or appear to change dynamically.

A brief comparison of polygenic risk scores and Mendelian randomisation.

Mendelian randomisation and polygenic risk score analysis have become increasingly popular in the last decade due to the advent of large-scale genome-wide association studies. Each approach has valuable applications, some of which are overlapping, yet there are important differences which we describe here.

Hypertensive disorders of pregnancy and midlife maternal cognition in a prospective cohort study.

Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of cardiovascular disorders, with recent evidence linking pre-eclampsia with vascular dementia. We examined associations of HDP with cognitive performance measured in midlife, in a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Six cognitive function domains were measured 20 years after pregnancy at a mean age of 51 years. The cognition tests were repeated at clinics in the following two years. Cognitive function domains measured were immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence, and verbal fluency. Exposures were pre-eclampsia, gestational hypertension (GH), and a combined category of any HDP, all compared to normotensive pregnancy. Of 3393 pregnancies included in the analysis, GH was experienced by 417 (12.3%) and pre-eclampsia by 57 (1.7%). GH was associated with lower verbal episodic memory, in the delayed logic memory test (-0.16 SDs; 95% CI -0.30, -0.03; p = .015) and there was weak evidence of an association with the immediate logic memory test (-0.13 SDs; -0.27, 0.001; p = .058). However, we did not see steeper declines by age for women with GH and there was no evidence of associations with other cognitive domains or for pre-eclampsia with any domains. Results were not substantially changed after controlling for midlife blood pressure. Our findings suggest that a history of GH is associated with slightly reduced episodic memory 20 years after pregnancy, but we found no evidence of a quicker age-related decline compared to women with normotensive pregnancies.

Investigation of genetic determinants of cognitive change in later life.

Cognitive decline is a major health concern and identification of genes that may serve as drug targets to slow decline is important to adequately support an aging population. Whilst genetic studies of cross-sectional cognition have been carried out, cognitive change is less well-understood. Here, using data from the TOMMORROW trial, we investigate genetic associations with cognitive change in a cognitively normal older cohort. We conducted a genome-wide association study of trajectories of repeated cognitive measures (using generalised estimating equation (GEE) modelling) and tested associations with polygenic risk scores (PRS) of potential risk factors. We identified two genetic variants associated with change in attention domain scores, rs534221751 (p = 1 × 10-8 with slope 1) and rs34743896 (p = 5 × 10-10 with slope 2), implicating NCAM2 and CRIPT/ATP6V1E2 genes, respectively. We also found evidence for the association between an education PRS and baseline cognition (at >65 years of age), particularly in the language domain. We demonstrate the feasibility of conducting GWAS of cognitive change using GEE modelling and our results suggest that there may be novel genetic associations for cognitive change that have not previously been associated with cross-sectional cognition. We also show the importance of the education PRS on cognition much later in life. These findings warrant further investigation and demonstrate the potential value of using trial data and trajectory modelling to identify genetic variants associated with cognitive change.

Dementia prevention: the Mendelian randomisation perspective.

Understanding the causes of Alzheimer's disease and related dementias remains a challenge. Observational studies investigating dementia risk factors are limited by the pervasive issues of confounding, reverse causation and selection biases. Conducting randomised controlled trials for dementia prevention is often impractical due to the long prodromal phase and the inability to randomise many potential risk factors. In this essay, we introduce Mendelian randomisation as an alternative approach to examine factors that may prevent or delay Alzheimer's disease. Mendelian randomisation is a causal inference method that has successfully identified risk factors and treatments in various other fields. However, applying this method to dementia risk factors has yielded unexpected findings. Here, we consider five potential explanations and provide recommendations to enhance causal inference from Mendelian randomisation studies on dementia. By employing these strategies, we can better understand factors affecting dementia risk.

Effects of in-store marketing on food and beverage purchases: a longitudinal study of households with children.

OBJECTIVE: Most food retailers display foods in prominent locations as a marketing strategy (i.e. 'placement promotions'). We examined the extent to which households with children change their food and beverage purchases in response to these promotions. DESIGN: We analysed a novel dataset of all products promoted in two supermarkets from 2016 to 2017, including promotion dates and locations (e.g. aisle endcaps and front registers). We linked promotions to all purchases from the supermarkets from 2016 to 2017 by a cohort of households with children. We calculated the number of weekly promotions in each of thirteen food and beverage groups (e.g. bread; candy) and used fixed effects regressions to estimate associations between number of weekly promotions and households' weekly food purchases, overall and by Supplemental Nutrition Assistance Program (SNAP) participation. SETTING: Two large supermarkets in Maine, USA. PARTICIPANTS: Eight hundred and twenty-one households with children. RESULTS: Most promotions (74 %) were for less healthy foods. The most promoted food groups were sweet and salty snacks (mean = 131·0 promotions/week), baked goods (mean = 68·2) and sugar-sweetened beverages (mean = 41·6). Households generally did not change their food group purchases during weeks when they were exposed to more promotions for those groups, except that a 1-sd increase in endcap candy promotions (about 1 promotion/week) was associated with $0·19/week (about 14·5 %) increase in candy purchases among SNAP nonparticipants (adjusted P < 0·001). CONCLUSIONS: In-store placement promotions for food groups were generally not associated with purchases of promoted food groups, perhaps because exposure to unhealthy food marketing was consistently high. Substantial changes to in-store food marketing may be needed to promote healthier purchases.

Maternal vaccination provision in NHS maternity trusts across England.

BACKGROUND: Vaccinations for seasonal influenza and pertussis have been recommended for pregnant women in England since 2010 and 2012, respectively. Uptake rates are suboptimal with large regional variations. To improve uptake, from 2016 onwards maternity trusts were commissioned to offer pertussis (and other) vaccinations in addition to these being available in primary care. Since 2021, Covid-19 vaccination has also been recommended for pregnant women. Overall maternal vaccination rates are routinely available, but not the relative provision by maternity trusts. We aimed to describe the national picture of maternity trust provision of maternal vaccinations, including how the maternity trust vaccination programme has progressed. METHODS: Cross-sectional survey plus comparisons with 2017-18 figures for maternity trust provision of pertussis vaccination, and with UKHSA data for total pertussis vaccination. RESULTS: Twelve NHS commissioners participated (from 13/06/22 to 31/03/23) providing data for 120 (of a total 124) maternity trusts across England. All 120 (100%) trusts were commissioned to deliver influenza, and 107 (89%) to deliver pertussis vaccinations, though not all actually administered the vaccines; 29% offered Covid-19 vaccinations. For 2021-22 we found a mean of 25% (range 0-81.3%) women were vaccinated for pertussis (a large increase compared with previous estimates for 2017-18); and 11% (range 0-74.2%) for influenza, via their maternity trust. Commissioners reported a negative impact of the pandemic on routine vaccination provision. There was indication of efficiency by vaccinating women attending for other appointments. There are diverse mechanisms for reporting pertussis and influenza vaccinations administered at maternity trusts back to primary care, which may be inefficient for maternity staff workload and accuracy of data transfer (especially for pertussis). CONCLUSION: A high proportion of maternity trusts provide both pertussis and influenza vaccinations, despite a negative impact of the pandemic. Reasons for large between-trust variation in vaccination rates should be explored to improve uptake and equity.

The bidirectional effects between cognitive ability and brain morphology: A life course Mendelian randomization analysis.

Introduction: Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area. Methods: Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years). Results: The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability. Discussion: Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.

Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study.

BACKGROUND: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). METHODS: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. FINDINGS: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46-0.84), lower levels of body mass index (BMI) (ß = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (ß = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (ß = -0.29, 95% CI = -0.39 to -0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. INTERPRETATION: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. FUNDING: Funding information is provided in the Acknowledgements.

Artificial intelligence for dementia genetics and omics.

Genetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible omics signatures that differentiate between dementia subtypes? Can high-dimensional omics data identify improved biomarkers? How can genetics inform our understanding of causal status of dementia risk factors? And which biological processes are altered by dementia-related genetic variation? Artificial intelligence (AI) and machine learning approaches give us powerful new tools in helping us to tackle these challenges, and we review possible solutions and examples of best practice. However, their limitations also need to be considered, as well as the need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine. HIGHLIGHTS: We have identified five key challenges in dementia genetics and omics studies. AI can enable detection of undiscovered patterns in dementia genetics and omics data. Enhanced and more diverse genetics and omics datasets are still needed. Multidisciplinary collaborative efforts using AI can boost dementia research.

International adaptation and validation of the Pro-VC-Be: measuring the psychosocial determinants of vaccine confidence in healthcare professionals in European countries.

BACKGROUND: Healthcare professionals (HCPs) play an important role in vaccination; those with low confidence in vaccines are less likely to recommend them to their patients and to be vaccinated themselves. The study's purpose was to adapt and validate long- and short-form versions of the International Professionals' Vaccine Confidence and Behaviors (I-Pro-VC-Be) questionnaire to measure psychosocial determinants of HCPs' vaccine confidence and their associations with vaccination behaviors in European countries. RESEARCH DESIGN AND METHODS: After the original French-language Pro-VC-Be was culturally adapted and translated, HCPs involved in vaccination (mainly GPs and pediatricians) across Germany, Finland, France, and Portugal completed a cross-sectional online survey in 2022. A 10-factor multigroup confirmatory factor analysis (MG-CFA) of the long-form (10 factors comprising 34 items) tested for measurement invariance across countries. Modified multiple Poisson regressions tested the criterion validity of both versions. RESULTS: 2,748 HCPs participated. The 10-factor structure fit was acceptable to good everywhere. The final MG-CFA model confirmed strong factorial invariance and showed very good fit. The long- and short-form I-Pro-VC-Be had good criterion validity with vaccination behaviors. CONCLUSION: This study validates the I-Pro-VC-Be among HCPs in four European countries; including long- and short-form tools for use in research and public health.

Estimating Dementia Risk Using Multifactorial Prediction Models.

Importance: The clinical value of current multifactorial algorithms for individualized assessment of dementia risk remains unclear. Objective: To evaluate the clinical value associated with 4 widely used dementia risk scores in estimating 10-year dementia risk. Design, Setting, and Participants: This prospective population-based UK Biobank cohort study assessed 4 dementia risk scores at baseline (2006-2010) and ascertained incident dementia during the following 10 years. Replication with a 20-year follow-up was based on the British Whitehall II study. For both analyses, participants who had no dementia at baseline, had complete data on at least 1 dementia risk score, and were linked to electronic health records from hospitalizations or mortality were included. Data analysis was conducted from July 5, 2022, to April 20, 2023. Exposures: Four existing dementia risk scores: the Cardiovascular Risk Factors, Aging and Dementia (CAIDE)-Clinical score, the CAIDE-APOE-supplemented score, the Brief Dementia Screening Indicator (BDSI), and the Australian National University Alzheimer Disease Risk Index (ANU-ADRI). Main Outcomes and Measures: Dementia was ascertained from linked electronic health records. To evaluate how well each score predicted the 10-year risk of dementia, concordance (C) statistics, detection rate, false-positive rate, and the ratio of true to false positives were calculated for each risk score and for a model including age alone. Results: Of 465 929 UK Biobank participants without dementia at baseline (mean [SD] age, 56.5 [8.1] years; range, 38-73 years; 252 778 [54.3%] female participants), 3421 were diagnosed with dementia at follow-up (7.5 per 10 000 person-years). If the threshold for a positive test result was calibrated to achieve a 5% false-positive rate, all 4 risk scores detected 9% to 16% of incident dementia and therefore missed 84% to 91% (failure rate). The corresponding failure rate was 84% for a model that included age only. For a positive test result calibrated to detect at least half of future incident dementia, the ratio of true to false positives ranged between 1 to 66 (for CAIDE-APOE-supplemented) and 1 to 116 (for ANU-ADRI). For age alone, the ratio was 1 to 43. The C statistic was 0.66 (95% CI, 0.65-0.67) for the CAIDE clinical version, 0.73 (95% CI, 0.72-0.73) for the CAIDE-APOE-supplemented, 0.68 (95% CI, 0.67-0.69) for BDSI, 0.59 (95% CI, 0.58-0.60) for ANU-ADRI, and 0.79 (95% CI, 0.79-0.80) for age alone. Similar C statistics were seen for 20-year dementia risk in the Whitehall II study cohort, which included 4865 participants (mean [SD] age, 54.9 [5.9] years; 1342 [27.6%] female participants). In a subgroup analysis of same-aged participants aged 65 (±1) years, discriminatory capacity of risk scores was low (C statistics between 0.52 and 0.60). Conclusions and Relevance: In these cohort studies, individualized assessments of dementia risk using existing risk prediction scores had high error rates. These findings suggest that the scores were of limited value in targeting people for dementia prevention. Further research is needed to develop more accurate algorithms for estimation of dementia risk.