Dementia Risk Score Research Articles

Dementia risk scores in diverse populations.

Dementia risk scores in diverse populations.

Exploring the Relationship Between CAIDE Dementia Risk and EEG Signal Activity in a Healthy Population

Background: Accounting for dementia risk factors is essential in identifying people who would benefit most from intervention programs. The CAIDE dementia risk score is commonly applied, but its link to brain function remains unclear. This study aims to determine whether the variation in this score is associated with neurophysiological changes and cognitive measures in normative individuals. Methods: The sample comprised 38 participants aged between 54 and 79 (M = 67.05; SD = 6.02). Data were collected using paper-and-pencil tests and electroencephalogram (EEG) recordings in the resting state, channels FP1 and FP2. The EEG signals were analyzed using Power Spectral Density (PSD)-based features. Results: The CAIDE score is positively correlated with the relative power activation of the θ band and negatively correlated with the MMSE cognitive test score, and MMSE variations align with those found in distributions of EEG-extracted PSD-based features. Conclusions: The findings suggest that CAIDE scores can identify individuals without noticeable cognitive changes who already exhibit brain activity similar to that seen in people with dementia. They also contribute to the convergent validity between CAIDE and the risk of cognitive decline. This underscores the importance of early monitoring of these factors to reduce the incidence of dementia.

Dementia risk factors and cognitive function in a nationwide population-based sample aged 65+

Abstract Background Cognitive function is fundamental to healthy aging and independent living. As there is no cure for dementia, prevention of risk factors (e. g. physical inactivity, obesity, hypertension, diabetes, social isolation, depression) is crucial. The aim of our study was to analyze selected dementia risk factors and their association with cognitive function in people aged 65 years and older. Methods Cross-sectional data from the nationally representative examination Study on Health of Older People in Germany (Gesundheit 65+) conducted between 2022-2023 by the Robert Koch Institute (n = 1.493; 48% women; mean age 78.8 years). Cognitive function was assessed by the Letter Digit Substitution Test (LDST), a measure of general speed of information processing, and of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) 10-word list delayed recall (WLR), a measure of memory. Weighted associations between age, sex, education, dementia risk scores and z-standardized test scores were examined using linear regression analysis. Results Higher age, male sex and lower level of education were significantly associated with lower z-scores in both tests (all p < 0.001). In separate models, all adjusted for age, sex and education, social isolation was associated with lower performance on both LDST (ß=-0.22; 95% confidence interval -0.42, -0.01) and CERAD WLR (ß=-0.21; -0.41, -0.01); depressive symptoms were associated with lower LDST z-scores (ß=-0.40; -0.67, -0.13), and physical inactivity with lower CERAD WLR z-scores (ß=-0.12; -0.24, -0.01). Obesity, hypertension, and diabetes were not significantly associated with any test. Conclusions Our findings from this nationwide general population study of old and very old adults show a clustering of reduced cognitive function with social isolation, symptoms of mental health impairments, and physical inactivity in old age which call for coordinated intersectoral health promotion and prevention activities. Key messages • The clustering of reduced cognition with dementia risk factors calls for intersectoral health actions. • Limitations in cognition should only be defined by age-, sex-, and education-specific norms.

A novel electrocardiogram-based model for prediction of dementia: the Atherosclerosis Risk in Communities (ARIC) study

Abstract Background Current dementia prediction models, such as the UK Biobank Dementia Risk Score (UKBDRS, 12 variables), are limited by having variables that are difficult to obtain, subjectively measured, and self-reported. Although individual ECG parameters are linked to higher dementia risk, no study has combined multiple ECG parameters to create an ECG model for dementia prediction. Purpose Using data from the ARIC study, a prospective community-based cohort of Black and White participants in the USA that started in 1987-89, we created an ECG model (based on 7 pre-defined ECG parameters linked to dementia) and compared its model discrimination with the UKBDRS. Methods Participants without prevalent dementia from 2 baselines were included: Visit 4 (V4, 1996-98) and V5 (2011-13). Seven ECG parameters were examined: heart rate, abnormal P-wave terminal force in lead V1 (PTFV1), prolonged P wave duration, abnormal P wave axis, advanced interatrial block, left ventricular hypertrophy (LVH, Cornell voltage criteria), and corrected QT interval (QTc). Dementia cases were identified through 2019 using in-person and phone cognitive assessments, hospitalisation codes, and death certificates. Using a backward selection method (keeping variables with P<0.10 and age, since it is an important dementia risk factor), parsimonious Cox regression models were constructed for prediction of dementia over the longest available follow-up (V4: 23 years, V5: 8 years). Model discrimination of the ECG models and UKBDRS variables was evaluated by the Harrell’s C-statistic (95% CI). Results At V4, 11,520 participants (mean age, 62.8 ± 5.7 years; 56% women; 22% Black) were included; 2,427 developed dementia. At V5, 5,667 participants (mean age, 75.4 ± 5.1 years; 59% women; 22% Black) were included; 830 developed dementia. Figures 1 and 2 show the C-statistic (95%) and area under the ROC curve for the ECG model and UKBDRS variables at V4 and V5, respectively. The C-statistic (95% CI) for both ECG models were >0.70 and comparable with the corresponding UKBDRS models. Conclusion For middle-aged and older adults, a dementia prediction model comprising age and 4 ECG variables has good discrimination for dementia that is comparable with the 12-variable UKBDRS model. Since ECG variables are easily obtainable and objectively measured, these ECG models will be easier to adopt than the UKBDRS model. Further work to validate this model in an external cohort and develop a risk score will facilitate clinical translation.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational randomised controlled effectiveness-implementation trial

Abstract Background The expected increase of dementia prevalence in the coming decades will mainly be within low-and middle-income countries and those with low socioeconomic status (SES) in high income countries. Forty percent of dementia is associated with modifiable, lifestyle-related cardiovascular risk factors. Mobile health interventions with remote coaching can help reach underserved high-risk populations globally. 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 persons aged 55-75 years of low SES in UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in CAIDE dementia risk score (including age, education, sex, systolic blood pressure, total cholesterol, BMI, physical exercise) after 12-18 months of intervention. Main implementation outcomes were coverage, acceptability, appropriateness, adoption, feasibility, sustainability, fidelity, and costs using a mixed methods approach. Findings Between 15th January 2021 and 18th April 2023, 1,488 persons were included and randomised (734 intervention, 754 control), with 1,229 (82·6%) available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months, the mean CAIDE score improved by 0·16 points in the intervention group vs. 0·01 in the control group (Mean Difference (MD) 0·16, 95% Confidence Interval (CI) 0·03-0·29). The effect was larger in those who adhered to the intervention (MD 0·27, 95%CI 0·12-0·44) and those planning to change lifestyle (MD 0·33, 95%CI 0·10-0·57). Ten percent of those invited participated; of these, 81% adopted the intervention and 50% continued active participation throughout the study. For the individual components of the CAIDE score, there were no statistically significant differences for systolic blood pressure, total cholesterol and BMI, but in the intervention group physical inactivity was reduced more than in the control group (MD 6·7%, 95%CI 2·1 to 11·2) and more participants quit smoking (MD -3·1%, 95%CI -4·8 to -1·5). Interpretation A coach-supported mHealth intervention to improve lifestyle is modestly effective in reducing dementia risk factors in those with low SES in the UK and any SES in China. Implementation is challenging in these populations, but those reached actively participated. Whether this will result in less cognitive decline and dementia requires a larger RCT with long follow-up.

Dementia risk scores, apolipoprotein E, and risk of Alzheimer's disease: One size does not fit all.

Evaluating the generalizability of dementia risk scores, primarily developed in non-Latinx White (NLW) participants, and interactions with genetic risk factors in diverse populations is crucial for addressing health disparities. We analyzed the association of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) and modified CAIDE (mCAIDE) scores with dementia risk using logistic regression models stratified by race/ethnicity in National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), and assessed their interaction with apolipoprotein E (APOE). Higher CAIDE scores were associated with an increased risk of dementia in Asian, Latinx, and NLW participants but not in Black participants. In contrast, higher mCAIDE scores were also associated with an increased risk of dementia in Black participants. Unfavorable mCAIDE risk profiles exacerbated the apolipoprotein E*ε4 (APOE*ε4) risk effect and attenuated the APOE*ε2 protective effect. Our findings underscore the importance of evaluating the validity of dementia risk scores in diverse populations for their use in personalized medicine approaches to promote brain health. Dementia risk scores demonstrate race/ethnic-specific effects on dementia risk. Unfavorable modifiable risk profiles moderate the effect of APOE on dementia risk. Dementia risk scores need to be validated in diverse populations.

External validation of dementia prediction models in Black or African American and White older adults: A longitudinal population-based study in the United States.

Identifying people at high risk of Alzheimer's disease (AD) dementia allows for timely intervention, which, if successful, will result in preventing or delaying the onset of the disease. Utilizing data from the Chicago Health and Aging Project (CHAP; n=2130), we externally evaluated four risk-prediction models for AD dementia, including Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), Australian National University Alzheimer's Disease Risk Index (ANU-ADRI), Brief Dementia Screening Indicator (BDSI), and Dementia Risk Score (DRS), in Black or African American and White adults. BDSI had the highest discriminate abilities for AD dementia (c-statistics of 0.79 in Black and 0.77 in White adults), followed by ANU-ADRI, within the age range and follow-up period of the original development cohort. CAIDE had the lowest discriminating power (c-statistic≤0.55). With increasing follow-up periods (i.e., 10-15 years), the discrimination abilities for all models declined. Because of racial disparities in AD dementia and longer preclinical and prodromal stages of disease development, race-specific models are needed to predict AD risk over 10 years. Utilizing risk-prediction models to identify individuals at higher risk of Alzheimer's disease (AD) dementia could benefit clinicians, patients, and policymakers. Clinicians could enroll high-risk individuals in clinical trials to test new risk-modifiable treatments or initiate lifestyle modifications, which, if successful, would slow cognitive decline and delay the onset of the disease. Current risk-prediction models had good discriminative power during the first 6 years of follow-up but decreased with longer follow-up time. Acknowledging the longer preclinical phase of AD dementia development and racial differences in dementia risk, there is a need to develop race-specific risk-prediction models that can predict 10 or 20 years of risk for AD and related dementias.

Development and validation of the Florey Dementia Risk Score web-based tool to screen for Alzheimer's disease in primary care

It is estimated that ∼60% of people with Alzheimer's disease (AD) are undetected or undiagnosed, with higher rates of underdiagnosis in low-to middle-income areas with limited medical resources. To promote health equity, we have developed a web-based tool that utilizes easy-to-collect clinical data to enhance AD detection rate in primary care settings. This study was leveraged on the data collected from participants of the Australian Imaging, Biomarker & Lifestyle (AIBL) study and the Religious Orders Study and Memory and Aging Project (ROSMAP). The study included three phases: (1) constructing and evaluating a model on retrospective cohort data (1407 AIBL participants), (2) performing simulated trials to assess model accuracy (30 AIBL participants) and missing data tolerability (30 AIBL participants), and (3) external evaluation using a non-Australian dataset (500 ROSMAP participants). The auto-score machine learning algorithm was employed to develop the Florey Dementia Risk Score (FDRS). All the simulated trials and evaluation were performed using a web-based FDRS tool. FDRS achieved an area under the curve (AUC) of approximately 0.82 [95% CI, 0.75-0.88], with a sensitivity of 0.74 [0.60-0.86] and a specificity of 0.73 [0.70-0.79]. The accuracy of the simulated pilot trial for 30 AIBL participants with complete record was 87% (26/30 correct), while it only slightly decreased (80.0-83.3%, depending on imputation methods) for another 30 AIBL participants with one or two missing data. FDRS achieved an AUC of 0.82 [0.77-0.86] of 500 ROSMAP participants. The FDRS tool offers a potential low-cost solution to AD screening in primary care. The present study warrants future trials of FDRS for optimization and to confirm its generalizability across a more diverse population, especially people in low-income countries. National Health and Medical Research Council, Australia (GNT2007912) and Alzheimer's Association, USA (23AARF-1020292).

Blood-based multivariate methylation risk score for cognitive impairment and dementia.

The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P=2.0×10-3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning=2.47) and Parkinson's disease (hazard ratio for MCI/dementia=2.59). Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level.

Potential for reducing dementia risk: association of the CAIDE score with additional lifestyle components from the LIBRA score in a population at high risk of dementia

Objectives Various dementia risk scores exist that assess different factors. We investigated the association between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score and modifiable risk factors in the Lifestyle for Brain Health (LIBRA) score in a German population at high risk of Alzheimer’s disease. Method Baseline data of 807 participants of AgeWell.de (mean age: 68.8 years (SD = 4.9)) were analysed. Stepwise multivariable regression was used to examine the association between the CAIDE score and additional risk factors of the LIBRA score. Additionally, we examined the association between dementia risk models and cognitive performance, as measured by the Montreal Cognitive Assessment. Results High cognitive activity (β = −0.016, p < 0.001) and high fruit and vegetable intake (β = −0.032, p < 0.001) correlated with lower CAIDE scores, while diabetes was associated with higher CAIDE scores (β = 0.191; p = 0.032). Although all were classified as high risk on CAIDE, 31.5% scored ≤0 points on LIBRA, indicating a lower risk of dementia. Higher CAIDE and LIBRA scores were associated with lower cognitive performance. Conclusion Regular cognitive activities and increased fruit and vegetable intake were associated with lower CAIDE scores. Different participants are classified as being at-risk based on the dementia risk score used.

Dementia Risk Scores, APOE, and risk of Alzheimer disease: one size does not fit all.

Evaluating the generalizability of dementia risk scores, primarily developed in non-Latinx White (NLW) participants, and interactions with genetic risk factors in diverse populations is crucial for addressing health disparities. We analyzed the association of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) and modified CAIDE (mCAIDE) scores with dementia risk using logistic regression models stratified by race/ethnicity in NACC and ADNI, and assessed their interaction with APOE. Higher CAIDE scores were associated with an increased risk of dementia in Asian, Latinx, and NLW participants but not in Black participants. In contrast, higher mCAIDE scores were also associated with an increased risk of dementia in Black participants. Unfavorable mCAIDE risk profiles exacerbated the APOE*ε4 risk effect and attenuated the APOE*ε2 protective effect. Our findings underscore the importance of evaluating the validity of dementia risk scores in diverse populations for their use in personalized medicine approaches to promote brain health.

Modifiable and Non-Modifiable Risk Factors for Dementia Among Non-Hispanic White and Black Populations Aged 50-64 in the United States, 2006-2016.

Non-Hispanic Black populations (NHB) have a significantly higher prevalence of dementia than non-Hispanic Whites in the U.S., and the underlying risk factors may play a role in this racial disparity. We aimed to calculate risk scores for dementia among non-Hispanic White (NHW) and non-Hispanic Black populations aged 50-64years over a period of 10years, and to estimate potential differences of scores between NHW and NHB. The Health and Retirement Study from 2006 to 2016 was used to calculate the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score, a validated score for predicting dementia risk. Weighted average CAIDE score, as well as CAIDE score for modifiable factors hypertension, obese, hypercholesterolemia, physical inactivity), and non-modifiable factors (age, sex, education) were calculated for adults aged 50-64years with normal cognition for 2006-2008, 2010-2012, 2014-2016. The associations of race with CAIDE score and elevated CAIDE score were examined. A total of 10,871 participants were included in the analysis. The CAIDE score showed declining trends for NHB from 2006 to 2016, while NHB consistently had a higher total CAIDE score and CAIDE score for modifiable factors from 2006 to 2016, but not for non-modifiable factors. NHB had a higher level of dementia risk factors than NHW among adults aged 50-64years in the U.S. from 2006 to 2016, and the difference is attributable to modifiable risk factors, which holds promise for risk reduction of dementia.

Association of modified dementia risk score with cerebrospinal fluid biomarkers and cognition in adults without dementia.

This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation. Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline. The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aβ42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aβ42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001). The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

Effects of a multidomain intervention against cognitive decline on dementia risk profiles - Results from the AgeWell.de trial.

Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention. Secondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication, and physical, social, and cognitive activity) in older adults with increased dementia risk. We analyzed data from n=461 participants with complete information on risk/protective factors comprised by LIBRA at the 24-month follow-up. Intervention effects on LIBRA and LIBRA components were assessed using generalized linear models. The intervention reduced LIBRA scores, indicating decreased dementia risk at follow-up (b=-0.63, 95% confidence interval [CI]: -1.14, -0.12). Intervention effects were particularly due to improvements in diet (odds ratio [OR]: 1.60, 95% CI: 1.16, 2.22) and hypertension (OR: 1.61, 95% CI: 1.19, 2.18). The AgeWell.de intervention reduced dementia risk. However, several risk factors did not improve, possibly requiring more intensive interventions. The AgeWell.de intervention reduced dementia risk according to LIfestyle for BRAin health (LIBRA) scores. Beneficial effects on LIBRA are mainly due to changes in diet and blood pressure. A pragmatic lifestyle intervention is apt to reduce dementia risk in an at-risk population.

The Importance of Knowledge on Dementia Risk Factors in the General Public: A Cross-Sectional Study.

The purpose of this study was to determine the influence of knowledge and beliefs on beneficial behaviors and dementia risk scores. A online survey was conducted among Chinese community residents over 18 years old. Multivariate logistic regression was used to identify the impact of knowledge and beliefs on dementia risk scores and beneficial behaviors. The respondents were 760 adults (mean age = 47.6 years, 60.8% female). Knowledge and beliefs were associated with cognitive activities (knowledge, odds ratio [OR] = 1.04; beliefs, OR = 1.17) and dementia risk scores (knowledge, OR = 0.95; beliefs, OR = 0.82). Additionally, lower perceived susceptibility (OR = 1.68; 95% CI, 1.04 to 2.72) and higher perceived benefits (OR = 0.68; 95% CI, 0.57 to 0.80) were associated with lower dementia risk scores. Knowledge and beliefs can promote beneficial behaviors and reduce dementia risk. In particular, perceptions of dementia susceptibility and benefits should be enhanced, which will greatly reduce dementia risk in the general public.

A Pilot Study of BRAIN BOOTCAMP, a Low-Intensity Intervention on Diet, Exercise, Cognitive Activity, and Social Interaction to Improve Older Adults’ Dementia Risk Scores

BackgroundLittle is known about the impact of short, low-intensity multidomain dementia risk reduction interventions in older adults.ObjectivesTo examine the effectiveness and feasibility of a low-intensity multidomain lifestyle intervention on dementia risk and dementia literacy in Australian older adults.DesignSingle-group pre-post design.SettingCommunity-dwelling.ParticipantsA total of 853 older Australians (Mean age=73.3 years, SD=6.1) recruited from the community.InterventionA 3-month dementia risk reduction program, BRAIN BOOTCAMP, including education, personalised risk information, physical cues for healthier choices and goal setting and planning to target four modifiable risk factors of diet, exercise, cognitive activity and social interaction in older adults.MeasurementsThe ‘LIfestyle for BRAin health’ (LIBRA) index was used to assess participants’ modifiable dementia risk based on 12 factors, with higher scores indicating greater risk. Dementia literacy was measured using a modified questionnaire derived from Dutch and British surveys, encompassing knowledge, risk reduction, and awareness aspects. Paired t-tests were used to compare dementia risk scores and dementia literacy before and after the program. Multivariate regressions were performed to identify sociodemographic and psychological factors associated with change in the LIBRA index.ResultsProgram attrition was high (58.3%). Participants who completed the program had decreased dementia risk scores (Cohen’s d=0.59, p<0.001), increased dementia literacy and awareness (Cohen’s d=0.64, p<0.001) and increased motivation to change lifestyle behaviors (Cohen’s d=0.25–0.52, p<0.016). Participants with higher motivational beliefs had greater dementia risk reduction.ConclusionsImproving older adults’ motivation and knowledge may help modify lifestyle behaviors to reduce dementia risk. However, program attrition remains a challenge, suggesting the need for strategies to enhance participant engagement and retention in such interventions.

CAIDE Score, Alzheimer's Disease Pathology, and Cognition in Cognitively Normal Adults: The CABLE Study.

Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score serves as a credible predictor of an individual's risk of dementia. However, studies on the link of the CAIDE score to Alzheimer's disease (AD) pathology are scarce. To explore the links of CAIDE score to cerebrospinal fluid (CSF) biomarkers of AD as well as to cognitive performance. In the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, we recruited 600 cognitively normal participants. Correlations between the CAIDE score and CSF biomarkers of AD as well as cognitive performance were probed through multiple linear regression models. Whether the correlation between CAIDE score and cognitive performance was mediated by AD pathology was researched by means of mediation analyses. Linear regression analyses illustrated that CAIDE score was positively associated with tau-related biomarkers, including pTau (p < 0.001), tTau (p < 0.001), as well as tTau/Aβ42 (p = 0.008), while it was in negative association with cognitive scores, consisting of MMSE score (p < 0.001) as well as MoCA score (p < 0.001). The correlation from CAIDE score to cognitive scores was in part mediated by tau pathology, with a mediation rate varying from 3.2% to 13.2% . A higher CAIDE score, as demonstrated in our study, was linked to more severe tau pathology and poorer cognitive performance, and tau pathology mediated the link of CAIDE score to cognitive performance. Increased dementia risk will lead to cognitive decline through aggravating neurodegeneration.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational, randomised, controlled effectiveness–implementation trial

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. 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. 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. 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. EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. For the Mandarin translation of the abstract see Supplementary Materials section.

Social Environment, Lifestyle, and Genetic Predisposition With Dementia Risk: A Long-Term Longitudinal Study Among Older Adults.

The role of social environment, that is, the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. We developed a novel polysocial risk score for dementia based on 19 SDOH among 5199 participants in the Health and Retirement Study, United States, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. The study participants (mean age = 73.4 years, SD = 8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1089 participants developed dementia. Every 1-point increase in the polysocial risk score (ranging from 0 to 10) was associated with a 21.6% higher risk (adjusted hazard ratio [aHR] = 1.21, 95% confidence intervals [95% CI] = 1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43%-60% lower risk of developing dementia (p < .001). In addition, African Americans were 1.3 times (aHR = 2.28, 95% CI = 1.96-2.66) more likely to develop dementia than European Americans, other things being equal. An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.

The Role of Genomic-Informed Risk Assessments in Predicting Dementia Outcomes.

By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health. To develop a genomic-informed risk assessment composed of family history, genetic, and clinical risk factors and, in turn, evaluate how the risk assessment predicted incident dementia. This longitudinal study included data from two clinical case-control cohorts with an average of 6.6 visits. Secondary analyses were conducted from July 2023 - March 2024. Data were previously collected across multiple US locations from 1994 to 2023. Older adults aged 55+ with whole-genome sequencing and dementia-free at baseline. An additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, APOE genotype, and an AD polygenic risk score. The risk of progression to all-cause dementia was evaluated using Cox-proportional hazard models (hazard ratios with 95% confidence intervals [OR 9%CI]). A total of 3,429 older adults were included (aged 75 ± 7 years; 59% female; 75% non-Latino White, 15% Black, 5.2% Latino, 3.6% other, and 0.4% Asian; 27% MCI), with 751 participants progressing to dementia. The most common high-risk indicator was a family history of dementia (56%), followed by APOE*ε4 genotype (36%), high mCAIDE score (34%), and high AD-PRS (11%). Most participants had at least one high-risk indicator, with 39% having one, 32% two, 9.8% three, and 1% four. The presence of 1, 2, 3, or 4 risk indicators was associated with a doubling (HR = 1.72, CI: 1.34-2.22, p = 2.5e-05), tripling (HR = 3.09, CI: 2.41-3.95, p = 4.4e-19), quadrupling (HR = 4.46, CI: 3.34-5.94, p = 2.2e-24), and a twelvefold increase (HR = 12.15, CI: 7.33-20.14, p = 3.2e-22) in dementia risk. We found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia.