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Background and Objectives: Observational research has shown that a substantial proportion of all dementia cases worldwide are attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the Lifestyle for Brain Health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population., Methods: Cross-sectional data were used from the observational population-based cohort of The Maastricht Study. The weighted compound score of LIBRA (including 12 dementia risk and protective factors, e.g., hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, gray matter, and CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in 3 domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SDs below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modeling were used, adjusted for age, sex, education, intracranial volume, and type 2 diabetes., Results: Participants (n = 4,164; mean age 59 years; 49.7% men) with higher LIBRA scores (mean 1.19, range -2.7 to 9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β = 0.051, p = 0.002) and lower scores on information processing speed (β = -0.067, p = 0.001) and executive function and attention (β = -0.065, p = 0.004). Only in men, associations between LIBRA score and volumes of gray matter (β = -0.093, p < 0.001) and CSF (β = 0.104, p < 0.001) and memory (β = -0.054, p = 0.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA score and cognition., Discussion: Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology, and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored., Classification of Evidence: This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores in some cognitive domains and a higher risk of cognitive impairment., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Background: The "LIfestyle for BRAin health" (LIBRA) index was recently updated with three new modifiable factors: hearing impairment, social contact, and sleep (LIBRA2), but has not yet been validated. Objective: Comparison of the performance of both LIBRA versions in predicting dementia risk. Methods: Longitudinal data from the English Longitudinal Study of Ageing (ELSA) and the Maastricht Aging Study (MAAS) were used. The weighted LIBRA (11/12 factors available) and LIBRA2 (14/15 factors available) scores were calculated, with higher scores representing an unhealthier lifestyle. Dementia diagnoses were based on self- or informant reported physician diagnosis, an informant-based cognitive screening tool, registry data or test data. Cox-proportional hazards regression was used to investigate the association between LIBRA(2) scores and dementia risk. Model fit and predictive accuracy were determined using the Akaike information criterion and Harrell's C index. Results: Over an average follow-up of 8.3 years in ELSA and 17.9 years in MAAS, 346 (4.6%) and 120 (8.5%) individuals developed dementia, respectively. In ELSA, a one-point increase in LIBRA2 was associated with an 8% (1.06–1.11) higher dementia risk (LIBRA: 13%, 1.09–1.16). In MAAS, a one-point increase in LIBRA2 was associated with a 6% (1.01–1.12) higher dementia risk (LIBRA: 8%, 0.99–1.16). In ELSA, LIBRA (Harrell's C = 0.68) and LIBRA2 (Harrell's C = 0.67) performed similarly. In MAAS, LIBRA2 (Harrell's C = 0.62) performed better compared to LIBRA (Harrell's C = 0.52) Conclusions: LIBRA2 is a better model for identifying individuals at increased dementia risk and for public health initiatives aimed at dementia risk reduction. [ABSTRACT FROM AUTHOR]

ObjectiveRenal dysfunction has been linked with increased risk for cognitive impairment and dementia, but studies are conflicting. For that reason, the aim of the present systematic review and meta-analysis is to summarize the best available evidence on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia.MethodsMedline, Embase, and Cochrane Database of Systematic Reviews were searched for potential publications until August 1, 2016. Studies were eligible if they fulfilled the following criteria: population-based study, prospective design, ≥100 participants, aged ≥45 years, ≥1 year follow-up, and cognition/dementia outcomes. Where appropriate, random effects meta-analyses were conducted yielding pooled odds ratios (OR) and 95% confidence intervals (CI).ResultsTwenty-two out of 8,494 abstracts fulfilled the eligibility criteria. Sufficient evidence was found for albuminuria, mixed results for estimated glomerular filtration rate (eGFR), insufficient support for cystatin C, and tentative evidence for serum creatinine and creatinine clearance. Meta-analyses of 5 studies representing 27,805 persons showed a 35% increased risk of cognitive impairment or dementia in those with albuminuria (OR 1.35, 95% CI 1.06-1.73, p = 0.015), whereas eGFR

Objectives: This study investigated whether the association between modifiable dementia risk and rate of cognitive decline differs across socioeconomic status (SES) strata. Design, setting and participants: Data were used from Maastricht Aging Study, a prospective cohort study with a 12-year follow-up. The baseline sample consisted of 1023 adults over 40 years old. Measurements: The "LIfestyle for BRAin health" (LIBRA) index was used to assess modifiable dementia risk. Cognitive performance was assessed at baseline, 6 and 12 years, and measured in the domains of information processing speed, executive functioning and verbal memory function. An SES score was calculated from equivalent income and educational level (tertiles). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline. Results: Participants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X2 = 7.08, P = 0.029; vs. high SES: X2 = 9.49, P = 0.009) and verbal memory (vs. middle SES: X2 = 9.28, P < 0.001; vs. high SES: X2 = 16.68, P < 0.001) over 6 years compared to their middle- and high-SES counterparts. Higher (unhealthier) LIBRA scores were associated with more decline in information processing speed (X2 = 12.66, P = 0.002) over 12 years and verbal memory (X2 = 4.63, P = 0.032) over 6 years. No consistent effect modification by SES on the association between LIBRA and cognition was found. Conclusions: Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavorable modifiable risk score suggesting more potential for lifestyle-based interventions. [ABSTRACT FROM AUTHOR]

Background: Dementia risk reduction is a public health priority, but interventions that can be easily implemented in routine care are scarce. Objective: To evaluate the feasibility of integrating dementia risk reduction in regular consultations in primary care and the added value of a dedicated smartphone app ('MyBraincoach'). Methods: 188 participants (40–60 years), with modifiable dementia risk factors were included from ten Dutch general practices in a cluster-randomized trial (NL9773, 06/10/2021). Practices were randomly allocated (1 : 1) to provide a risk-reduction consultation only or to additionally provide the app. During the consultation, participants learned about dementia risk reduction and how to improve their risk profile. The app group received daily microteaching-notifications about their personally relevant risk factors. Feasibility was evaluated after 3 months using questionnaires assessing knowledge on dementia risk reduction and health behavior change. The primary outcome was change in the validated "LIfestyle for BRAin health" (LIBRA) score. In-depth interviews were conducted with participants and primary care providers (PCPs). Results: The interventions were positively perceived, with 72.0% finding the consultation informative and 69.2% considering the app useful. Drop-out was low (6.9%). LIBRA improved similarly in both groups, as did Mediterranean diet adherence and body mass index. Knowledge of dementia risk reduction increased, but more in the app group. Interviews provided insight in participants' and PCPs' needs and wishes. Conclusions: Integrating dementia risk reduction in primary care, supported by a smartphone app, is a viable approach towards dementia risk reduction. Larger trials are needed to establish (cost-)effectiveness. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances have been linked with cognitive decline and a higher risk of dementia. However, there is a lack of studies with sufficient follow-up duration, a detailed neuropsychological assessment and adequate control of main confounders. Objective: To investigate the relation between self-reported sleep quality and cognitive decline over 12 years in cognitively healthy individuals from the general population. Methods: We used data from the Maastricht Aging Study (MAAS), a Dutch population-based prospective cohort study of 1,823 community-dwelling adults aged 24 to 82 years at baseline. Cognitive performance was measured at baseline, 6 and 12 years on verbal memory, executive functions, and information processing speed. Sleep quality was assessed at baseline using the sleep subscale score of the 90-item Symptom Checklist (SCL-90). Additional modifiable dementia risk factors were summarized in the LIfestyle for BRAin health (LIBRA) risk score. Weighted linear mixed models tested the association between continuous scores and tertiles of subjective sleep quality and change in cognitive performances over time. Models were adjusted for age, gender, educational level, LIBRA, and use of hypnotic (sleep) medication. Results: Worse sleep quality was associated with faster decline in processing speed. At older age (≥65 years), it was also associated with faster decline in verbal memory. Association were independent of other modifiable dementia risk factors and use of hypnotic medication. Directionally similar but non-significant associations were found between worse sleep quality and executive functions. Conclusions: In this population-based study across the adult age range, poor self-reported sleep was associated with accelerated cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods: We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score. Results: During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)]. Conclusions: Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist. [ABSTRACT FROM AUTHOR]

Background: Health- and lifestyle factors account for a substantial part of all dementia cases, which opens the opportunity for primary prevention. However, the required behavioral change is complex and involves targeting multiple risk factors. mHealth interventions can potentially contribute to improving motivation in a low-cost and scalable way. Objective: To explore usage patterns, appreciation, and beliefs and attitudes regarding dementia risk reduction during the use of the MyBraincoach mobile app. Methods: Participants were community-dwelling middle-aged adults from the Netherlands and used either the standard (education) or extended (education+motivational triggers) app version for three months. Two panel studies were combined in this paper. Chi-square tests, t-tests and linear mixed models were used, adjusted for age, sex, and education. Results: Of all participants (n = 299, 50.2% male), 167 (55.9%) had installed the app. The most reported reason for non-use was technical problems (47%). Those who used the app were at baseline already more positive about dementia risk reduction than those who did not use the app. Of all users who completed the evaluation (n = 102), 78.4% (n = 80) stated that the app provided a positive approach towards brain health and 80.4% (n = 82) felt better informed. Younger (<60y) and lower educated participants evaluated the app most positively. Conclusion: Usage of the app was low, but users showed more positive beliefs and attitudes regarding dementia risk reduction. Most users evaluated the app positively and stated to have gained knowledge on the topic. Improving the use of the app must keep high priority in future studies. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular disease (CVD) has been suggested to accelerate cognitive decline and to be a risk factor for dementia, but still little is known about the cognitive course after a first cardiovascular event. Therefore, the present study aims to investigate the cognitive trajectories in both prevalent and incident CVD over a 12-year time period in the general population. Methods and results Cognitively healthy participants (age 24–82 years, n  = 1823) of a prospective cohort study were serially assessed at baseline, 6 and 12 years. Verbal memory, executive function, and information processing speed were analysed in adults with prevalent, incident, and no CVD. Random effects models were used to test the association between CVD and change in cognitive function over time. At baseline, participants with prevalent CVD showed more decline in memory and information processing speed than healthy controls. Participants with incident CVD also showed more decline in these cognitive domains, but this was only significant in the follow-up period from 6 to 12 years. Associations were more pronounced in participants aged younger than 65 years at baseline, and in sub-analyses with angina pectoris or myocardial infarction as the most prevalent CVD conditions. Conclusion Prevalent and incident CVD predict cognitive decline in middle-aged individuals. Findings for incident CVD suggest that the onset of decline is linked in time with the vascular event itself. Timely CVD management may delay the onset of decline. [ABSTRACT FROM AUTHOR]

Background: The total number of people affected by dementia worldwide is increasing rapidly. Recent studies provided evidence for the contribution of modifiable risk and protective factors to dementia risk. Although healthcare professionals could play an essential role in informing the general public about the relationship between lifestyle and dementia, it is unclear what they know about this relationship. Therefore, this study assesses the awareness of dementia risk reduction among current and future healthcare professionals. Design and methods: An online survey was carried out among 182 healthcare students from Maastricht University and 20 general practitioners (GPs) and practice nurses in Limburg, The Netherlands. The survey assessed the knowledge about risk and protective factors of dementia and identified needs, wishes and barriers concerning dementia risk reduction strategies. Results: The majority of current (75.0%) and future (81.9%) healthcare professionals indicated that dementia risk reduction is possible. Among students, awareness of cardiovascular risk factors of dementia (e.g., coronary heart disease (44.5%), hypertension (53.8%)) was low. Most participants (>70.0%) would like to receive more information about dementia risk reduction. Conclusions: The majority of current and future healthcare professionals were aware of the relationship between lifestyle and dementia risk. However, there are still substantial gaps in knowledge regarding individual dementia risk factors. Given the essential role of healthcare professionals in providing lifestyle advice, there is a need to increase awareness by providing educational programs focused on dementia risk reduction. [ABSTRACT FROM AUTHOR]

Introduction: Individuals in early dementia prevention trials may differ in how much they benefit from interventions depending on their initial risk level. Additionally, modifiable dementia risk scores might be used as surrogate/intermediate outcomes. Methods: In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated in post hoc analyses (N = 1207) whether the cognitive benefits of the 2‐year multi‐domain lifestyle intervention differed by baseline dementia risk measured with the "LIfestyle for BRAin Health" (LIBRA) score. We also investigated intervention effects on change in LIBRA score over time. Results: Overall, higher baseline LIBRA was related to less cognitive improvement over time. This association did not differ between the intervention and control groups. The intervention was effective in decreasing LIBRA scores over time, regardless of baseline demographics or cognition. Discussion: The cognitive benefit of the FINGER intervention was similar across individuals with different LIBRA scores at baseline. Furthermore, LIBRA may be useful as a surrogate/intermediate endpoint and surveillance tool to monitor intervention success during trial execution. [ABSTRACT FROM AUTHOR]

Objective: As no causal treatment for dementia is available yet, the focus of dementia research is slowly shifting towards prevention strategies. Therefore, this study aimed to examine the predictive accuracy of the "LIfestyle for BRAin Health" (LIBRA) score, a weighted compound score of 12 modifiable risk and protective factors, for dementia and mild cognitive impairment (MCI) in midlife and late-life, and in individuals with high or low genetic risk based on presence of the apolipoprotein (APOE) ε4 allele.Methods: The LIBRA score was calculated for participants from the Finnish Cardiovascular Risk Factors, Aging and Dementia (CAIDE) population-based study examined in midlife (n = 1024) and twice in late-life (n = 604) up to 30 years later. Diagnoses of MCI and dementia were made according to established criteria. Cox proportional hazards models were used to assess the association between LIBRA and risk of dementia and MCI in models adjusted for sex and education (age as timescale).Results: Higher midlife LIBRA scores were related to higher risk of dementia (hazard ratio [HR] = 1.27; 95% confidence interval [CI], 1.13-1.43) and MCI (unadjusted model: HR = 1.12; 95% CI, 1.03-1.22) up to 30 years later. Higher late-life LIBRA scores were related to higher risk of MCI (HR = 1.11; 95% CI, 1.00-1.25), but not dementia (HR = 1.02; 95% CI, 0.84-1.24). Higher late-life LIBRA scores were related to higher dementia risk among apolipoprotein E (APOE) ε4 non-carriers.Conclusions: Findings emphasize the importance of modifiable risk and protective factors for dementia prevention. [ABSTRACT FROM AUTHOR]

Background: Differences in dementia risk across the gradient of socioeconomic status (SES) exist, but their determinants are not well understood.Objective: This study investigates whether health conditions and lifestyle-related risk factors explain the SES inequalities in dementia risk.Methods: 6,346 participants from the English Longitudinal Study of Ageing were followed up from 2008/2009 until 2014/2015. We used Cox regression adjusted for age, gender, wealth/education, and clustering at the household level to examine the association between SES markers (wealth, education) and time to dementia in a structural equation model including potential mediation or effect modification by a weighted compound score of twelve modifiable risk and protective factors for dementia ('LIfestyle for BRAin health' (LIBRA) score).Results: During a median follow-up of 6 years, 192 individuals (3.0%) developed dementia. LIBRA scores decreased with increasing wealth and higher educational level. A one-point increase in the LIBRA score was associated with a 13% increase in dementia risk (hazard ratio (HR) = 1.13, 95% confidence interval 1.07-1.19). Higher wealth was associated with a decreased dementia risk (HR = 0.58, 0.39-0.85). Mediation analysis showed that 52% of the risk difference between the highest and lowest wealth tertile was mediated by differences in LIBRA (indirect effect: HR = 0.75, 0.66-0.85). Education was not directly associated with dementia (HR = 1.05, 0.69-1.59), but was a distal risk factor for dementia by explaining differences in wealth and LIBRA scores (indirect effect high education: HR = 0.92, 0.88-0.95).Conclusion: Socioeconomic differences in dementia risk can be partly explained by differences in modifiable health conditions and lifestyle factors. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between modifiable risk and protective factors and severe cognitive impairment and dementia in the very old. Additionally, the present study tests the predictive validity of the 'LIfestyle for BRAin health' (LIBRA) score, an index developed to assess an individual's dementia prevention potential. Method: Two hundred seventy-eight individuals aged 85 years or older from the Cambridge City over-75s cohort study were followed-up until death. Included risk and protective factors were: diabetes, heart disease, hypertension, depression, smoking, low-to-moderate alcohol use, high cognitive activity, and physical inactivity. Incident severe cognitive impairment was based on the Mini-Mental State Examination (score: 0-17) and incident dementia was based on either post-mortem consensus clinical diagnostic assessments or death certificate data. Logistic regressions were used to test whether individual risk and protective factors and the LIBRA score were associated with severe cognitive impairment or dementia after 18 years follow-up. Results: None of the risk and protective factors or the LIBRA score was significantly associated with increased risk of severe cognitive impairment or dementia. Sensitivity analyses using a larger sample, longer follow-up period, and stricter cut-offs for prevalent cognitive impairment showed similar results. Conclusion: Associations between well-known midlife risk and protective factors and risk for severe cognitive impairment or dementia might not persist into very old age, in line with suggestions that targeting these factors through lifestyle interventions should start earlier in life. [ABSTRACT FROM AUTHOR]