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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 Hearing loss (HL) and visual loss (VL) are recently identified as promising dementia risk factors, but long-term studies with adequate control of other modifiable dementia risk factors are lacking. This 25-year follow-up study investigated the association between objectively measured HL and VL with cognitive decline and incident dementia. Methods 1823 participants (age 24–82 years) of the Maastricht Aging Study were assessed at baseline, 6, 12 and 25 years. Baseline HL was defined as pure-tone hearing loss ≥20 dB at frequencies of 1, 2 and 4 kHz and VL as binocular, corrected visual acuity <0.5. Associations with cognitive decline (verbal memory, information processing speed, executive function) and incident dementia were tested using linear mixed models and Cox proportional hazard models, respectively. Analyses were adjusted for demographics and 11 modifiable dementia risk factors (LIfestyle for BRAin health index). Results Participants with HL (n  = 520, 28.7%) showed faster decline in all cognitive domains than participants without HL. No consistent association was found for VL (n  = 58, 3.2%), but below-average visual acuity (<1) showed significant associations with information processing speed and executive function. No significant associations with dementia risk were found. Findings were independent of demographics and modifiable dementia risk factors. Conclusions HL predicts faster cognitive decline but not dementia risk in adults aged 24–82 years. VL shows no consistent associations, though below-average visual acuity is linked to faster cognitive decline. This study supports HL as an independent risk factor for cognitive decline. Future studies should further evaluate the roles of HL and VL in dementia risk reduction. [ABSTRACT FROM AUTHOR]

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]

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: Our work shows the potential of employing blood‐derived DNA methylation data in the assessment of dementia risk. Highlights: 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. [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: High cognitive activity possibly reduces the risk of cognitive decline and dementia. Aims: To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment. Method: Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors. Results: Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes. Conclusions: A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health. [ABSTRACT FROM AUTHOR]

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta‐analyses with a two‐round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. Highlights: An umbrella review was combined with opinions of 18 dementia experts.Various candidate targets for dementia risk reduction were identified.Experts prioritized hearing impairment, social contact, and sleep.Re‐assessment of dementia risk scores is encouraged.Future work should evaluate the predictive validity of updated risk scores. [ABSTRACT FROM AUTHOR]