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The author reflects on the need and importance of investing time and resources on the career development of early- and mid-career researchers (EMCR) in dementia. Topics include the need to invest in research capacity building, particularly in low- and middle-income countries (LMIC) and the urgency of filling the gaps in the care and prevention practices in relation to dementia around the world.

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: Dementia is a global health challenge. Currently, there is no curative treatment for dementia and therefore risk reduction through lifestyle modifications has become more prominent with high cognitive activity as a promising target. This study explored the association between an individual's need to engage in cognitively stimulating activities, brain damage and cognitive functioning in the Dutch general population. Method: This study used cross‐sectional data from the population‐based cohort The Maastricht Study (N = 4,209; mean age 59.06 ± 8.58 years, 50.11% women). Need For Cogntion (NFC) was measured with the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed and executive functioning and attention. Standardized volumes of white matter hyperintensities (WMH) and cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3 Tesla MRI. Multiple linear regression analysis was used to explore the association between NFC and cognitive functioning, NFC and WMH and NFC and CSF. Binary logistic regression analysis was used to assess the association between NFC and CSVD. Interaction between brain damage or cognitive impairment (a score of <1.5 standard deviation below the mean on any of the three cognitive domains) and NFC on cognitive functioning was tested by including interaction terms in the regression analyses. Result: High NFC was positively associated with cognitive functioning (β: 0.21, p = <0.001) and negatively associated with CSVD (OR: 0.74, p = 0.005). These associations were independent of demographic and somatic factors. A dose‐response relationship between NFC and cognitive functioning was observed. There was no statistically significant association between NFC and WMH or CSF. No interaction between CSVD, WMH or CSF and NFC on cognitive functioning was found. Cognitive impairment did not moderate the association between NFC and cognitive functioning. Conclusion: A high need for engaging in cognitively stimulating activities is associated with better cognitive functioning and less brain damage. This is in line with previous research. These results indicate that, in middle‐aged populations, stimulating cognitive activity may be an opportunity for risk reduction of cognitive decline and dementia. [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]

Background: There is consistent evidence for the contribution of modifiable risk factors to dementia risk, offering opportunities for primary prevention. Yet, most individuals are unaware of these opportunities., Objective: To investigate whether online education about dementia risk reduction may be a low-level means to increase knowledge and support self-management of modifiable dementia risk factors., Methods: A pre-post study was conducted with Dutch community-dwelling individuals who registered for a free e-learning course called "Keep your brain healthy". The e-learning covers seven themes delivered week-by-week covering cognitive and physical activity, diet, and cardiovascular health, amongst others. Participants completed an online survey before starting the e-learning, immediately afterwards, and three months later. The survey covered user experience, knowledge on dementia risk reduction, motivation for, and engagement in, health behaviors., Results: Of the 477 participants (70.9% women, mean age = 63 years), 339 (71.1%) completed the survey immediately after the e-learning, and 241 (50.5%) completed the three-month follow-up survey. User experiences were positive with weekly themes receiving average ratings between 7.9-8.1 out of 10. Improvements over time were seen in knowledge of dementia risk reduction, Mediterranean diet adherence, social contact satisfaction, and motivation for physical activity. Cognitive activity levels and alcohol consumption improved over time in women. Moreover, improvements in knowledge and Mediterranean diet adherence remained present three months after course completion., Conclusions: This e-learning program was positively perceived, increased knowledge of dementia risk reduction, and promoted engagement in brain-healthy lifestyles. The program can easily be implemented as a stand-alone tool or as part of larger dementia risk reduction initiatives.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research., Methods: The campaign entailed seven recruitment strategies referring to The Dutch Brain Research Registry (DBRR): (1) Facebook advertisements, (2) appearance on national television, (3) newspaper articles, (4) researcher outreach, (5) patient organizations, (6) search engines, and (7) other. For each strategy, we describe the number of individuals (a) registered, (b) potentially eligible, and (c) included in FINGER-NL. Subsequently, the efficiency, defined by the eligibility ratio (eligible/registered), and effectiveness, defined by the inclusion ratio (included/registered) were calculated. Associations between recruitment strategies and sociodemographic factors of underrepresented groups were tested with binomial logistic regressions., Results: The campaign resulted in 13,795 new DBRR registrants, of which n  = 3475 were eligible (eligibility ratio = 0.25) and n  = 1008 were included (inclusion ratio = 0.07). The Facebook advertisements and television appearance resulted in the highest numbers of registrants ( n  = 4678 and n  = 2182) which translated to the highest number of inclusions ( n  = 288 and n  = 262). The appearance on national television (eligibility ratio = 0.35), newspaper articles (0.26), and Facebook campaigns (0.26) were the most efficient strategies. The national television appearance (inclusion ratio = 0.13) was the most effective strategy. The Facebook campaign and appearance on national television performed relatively better in recruiting individuals from underrepresented groups., Discussion: A multipronged recruitment campaign via a national online recruitment registry is efficient and effective in recruiting and prescreening an adequate number of individuals aged 60-79 years with prevention potential for a multi-site intervention trial within a limited time frame of 15 months. Social media advertisements and television are preferred strategies to recruit individuals from underrepresented groups., Highlights: An online brain research registry recruited eligible participants successfully.Mass media recruitment strategies are efficient for reaching large numbers.Direct recruitment through researchers and patient organizations seems more effective.Online registries offer automated prescreening and alternatives for screen-failures.Tailored strategies are needed to reach underrepresented groups to improve diversity., Competing Interests: S.A.M.S. provided consultancy services to Prothena Biosciences, Aribio, and Biogen, and she is part of the Scientific Advisory Board of Cogstate. All funds are paid to the institution. W.M.F. has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. W.M.F. has been an invited speaker at Biogen MAInc, Danone, Eisai, Novonordisk, Web MD Neurology (Medscape), Springer Healthcare, European Brain Council. W.M.F. is consultant to Oxford Health Policy Forum CIC, Roche, Eisai, and Biogen MA Inc. W.M.F. participated on advisory boards of Biogen MAI inc, Roche, and EliLilly. All funding is paid to her institution. W.M.F. is a member of the steering committee of PAVE, and Think Brain Health. W.M.F. was associate editor of Alzheimer, Research & Therapy in 2020/2021. W.M.F. is associate editor at Brain. M.D.Z. is site coordinator of the phase 1/2 ASPIRE‐FTD clinical trial (NCT06064890) sponsored by AviadoBio. L.W., L.M.S., S.B., Y.M., O.R., N.S., J.M.O., E.S., K.D., Y.V.,R.A.A.H., and S.K. report no conflicts of interest. Author disclosures are available in the Supporting Information., (© 2025 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Different aspects of social relationships (e.g., social network size or loneliness) have been associated with dementia risk, while their overlap and potentially underlying pathways remain largely unexplored. This study therefore aimed to (1) discriminate between different facets of social relationships by means of factor analysis, (2) examine their associations with dementia risk, and (3) assess mediation by depressive symptoms., Methods: Thirty-six items from questionnaires on social relationships administered in Wave 2 (2004/2005) of the English Longitudinal Study of Ageing ( n = 7536) were used for exploratory and confirmatory factor analysis. Factors were then used as predictors in Cox proportional hazard models with dementia until Wave 9 as outcome, adjusted for demographics and cardiovascular risk factors. Structural equation modeling tested mediation by depressive symptoms through effect decomposition., Results: Factor analyses identified six social factors. Across a median follow-up time of 11.8 years (IQR = 5.9-13.9 years), 501 people developed dementia. Higher factor scores for frequency and quality of contact with children (HR = 0.88; p = 0.021) and more frequent social activity engagement (HR = 0.84; p < 0.001) were associated with lower dementia risk. Likewise, higher factor scores for loneliness (HR = 1.13; p = 0.011) and negative experiences of social support (HR = 1.10; p = 0.047) were associated with higher dementia risk. Mediation analyses showed a significant partial effect mediation by depressive symptoms for all four factors. Additional analyses provided little evidence for reverse causation., Conclusions: Frequency and quality of social contacts, social activity engagement, and feelings of loneliness are associated with dementia risk and might be suitable targets for dementia prevention programs, partly by lowering depressive symptoms.

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., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Several modifiable lifestyle risk factors for dementia have been identified, but it is unclear how much the Norwegian public knows about the relationship between lifestyle and brain health. Therefore, this study aimed to investigate knowledge about modifiable dementia risk and protective factors and beliefs and attitudes towards dementia and dementia risk reduction in a randomly selected subsample of the Norwegian population., Methods: The total sample (n = 1435) included individuals aged 40-70 years from four counties (Oslo, Innlandet, Nordland and Trøndelag) in Norway. Two online questionnaires were used to measure (1) awareness about dementia risk reduction and (2) an individual`s motivation to change behaviour for dementia risk reduction (MOCHAD-10)., Results: Of the participants, 70% were aware of the potential of dementia risk reduction in general. Physical inactivity (86%), cognitive inactivity (84%) and social isolation (80%) were the most frequently recognised dementia risk factors. On the other hand, diabetes (26%), coronary heart disease (19%), hearing loss (18%) and chronic kidney disease (7%) were less often recognised as dementia risk factors. Comparing men and women, the only significant difference was that women were more likely to report parents with dementia as a risk factor compared to men. Gender, age and educational differences were seen in beliefs and attitudes towards dementia prevention:women reported more negative feelings and attitudes towards dementia than men;those aged 40-49 years - more likely than older age groups - reported that 'knowing family members with dementia' or 'having risk factors' made them believe they had to change their lifestyle and behaviour., Conclusions: The results indicate that 70% of the Norwegian public are aware of the potential for dementia risk reduction in general. However, there are major gaps in existing knowledge, particularly for cardiovascular risk factors such as hypertension, coronary heart disease, hypercholesterolemia and metabolic factors (diabetes, obesity). These findings underline the importance of further informing the Norwegian public about lifestyle-related risk and protective factors of dementia. Differences in beliefs and attitudes towards dementia risk prevention by age, gender and education require tailored public risk reduction interventions., (© 2022. The Author(s).)

This study evaluates a public health campaign initiated by the Alzheimer Center Limburg of Maastricht University. The aim was to increase awareness of the influence of a healthy lifestyle on lowering the risk of dementia in community-dwelling inhabitants of the Province of Limburg (aged 40 - 75 years). The campaign used mass media and public events, supported by a campaign website and mobile application (MijnBreincoach app).  An additional district-oriented approach was chosen in the municipalities of Roermond, Landgraaf and Brunssum, in which local stakeholders were involved in the design and execution of campaign-related events. Population-level difference in awareness before and after the campaign was assessed in two independent samples. No pre-post difference was observed in the level of awareness of dementia risk reduction. An additional analyses in the post-campaign sample revealed that the group that reported to have heard of the campaign, was more often aware of dementia risk reduction and reported higher motivation for behavioural change than the group that had not heard of the campaign. The district-oriented approach resulted in better recognition of campaign-material and the mobile application. With regard to the individual lifestyle factors, healthy diet and physical activity were identified more often post-campaign. Cognitive activity was identified most often at both pre- and post-assessment, but there was no increase in awareness after the campaign.

Strategies to reduce dementia risk are needed to minimize the burden of this growing public health concern. Most individuals are not aware that dementia risk reduction is possible, let alone how this could be achieved. Health education, such as public awareness campaigns on the topic of dementia risk reduction, can meet this need. A public health campaign (including social media and offering an online individual risk assessment tool) was carried out over a 7-month period in Flanders, Belgium. Impact was assessed in two independent online surveys, before (n = 1003) and after the campaign (n = 1008), in representative samples of adults aged 40-75 years. Questions regarding personal needs, wishes and barriers were also included. After the campaign, more individuals (10.3%) were aware that dementia risk reduction is possible than before the campaign, and more individuals correctly identified 10 out of 12 surveyed modifiable dementia risk and protective factors. However, no differences were observed in low-educated individuals. Further, specific differences in potential needs, wishes and barriers for future campaigns or interventions were observed between demographic strata. The majority of the respondents (89%) indicated that they would welcome more information on improving their brain-health. More than half (54%) also believed that they lacked the necessary knowledge to make brain-healthy behavior changes. In conclusion, effective public awareness campaigns on the topic of dementia risk reduction are feasible and timely, given the state of the evidence. Special efforts need to be made to develop effective campaigns, tailored towards low-educated individuals., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Alzheimer's disease (AD) biomarkers such as amyloid, p-tau and neuronal injury markers have been associated with affective symptoms in cognitively impaired individuals, but results are conflicting., Methods: CINAHL, Embase, PsycINFO and PubMed were searched for studies evaluating AD biomarkers with affective symptoms in mild cognitive impairment and AD dementia. Studies were classified according to AT(N) research criteria., Result: Forty-five abstracts fulfilled eligibility criteria, including in total 8,293 patients (41 cross-sectional studies and 7 longitudinal studies). Depression and night-time behaviour disturbances were not related to AT(N) markers. Apathy was associated with A markers (PET, not CSF). Mixed findings were reported for the association between apathy and T(N) markers; anxiety and AT(N) markers; and between agitation and irritability and A markers. Agitation and irritability were not associated with T(N) markers., Discussion: Whereas some AD biomarkers showed to be associated with affective symptoms in AD, most evidence was inconsistent. This is likely due to differences in study design or heterogeneity in affective symptoms. Directions for future research are given., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: With 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 Findings: We 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., Conclusions: These 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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AEA is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. CB is a member of the Editorial Board of PLOS Medicine. HB is on the Advisory Board of Nutricia Australia. MG was on Biogen Inc’s “Patient Journey Advisory Group” in 2016 and 2017. NS reports personal fees from Merck Consumer Health and the NIH outside the submitted work. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. PSS received grant funding from the NIH/NIA (USA) and the NHMRC (Australia), as well as philanthropic funding through The Dementia Momentum. He is on the Australian Advisory Board of Biogen Pharmaceuticals. All other authors have declared that no competing interests exist.

Objective: APOE status has been associated to affective symptoms in cognitively impaired subjects, with conflicting results., Methods: Databases CINAHL, Embase, PsychINFO and PubMed were searched for studies evaluating APOE genotype with affective symptoms in MCI and AD dementia. Symptoms were meta-analyzed separately and possible sources of heterogeneity were examined., Results: Fifty-three abstracts fulfilled the eligibility criteria. No association was found between the individual symptoms and APOE ε4 carriership or zygosity. For depression and anxiety, only pooled unadjusted estimates showed positive associations with between-study heterogeneity, which could be explained by variation in study design, setting and way of symptom assessment., Conclusions: There is no evidence that APOE ε4 carriership or zygosity is associated with the presence of depression, anxiety, apathy, agitation, irritability or sleep disturbances in cognitively impaired subjects. Future research should shift its focus from this single polymorphism to a more integrated view of other biological factors., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Modifiable risk factors for dementia were recently identified and compiled in a systematic review. The 'Lifestyle for Brain Health' (LIBRA) score, reflecting someone's potential for dementia prevention, was studied in a large longitudinal population-based sample with respect to predicting cognitive change over an observation period of up to 16 years., Methods: Lifestyle for Brain Health was calculated at baseline for 949 participants aged 50-81 years from the Maastricht Ageing Study. The predictive value of LIBRA for incident dementia and cognitive impairment was examined by using Cox proportional hazard models and by testing its relation with cognitive decline., Results: Lifestyle for Brain Health predicted future risk of dementia, as well as risk of cognitive impairment. A one-point increase in LIBRA score related to 19% higher risk for dementia and 9% higher risk for cognitive impairment. LIBRA predicted rate of decline in processing speed, but not memory or executive functioning., Conclusions: Lifestyle for Brain Health (LIBRA) may help in identifying and monitoring risk status in dementia-prevention programmes, by targeting modifiable, lifestyle-related risk factors. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: Renal 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., Methods: Medline, 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)., Results: Twenty-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 <60 mL/min/1.73 m 2 showed no significant association (OR 1.28, 95% CI 0.99-1.65, p = 0.063). No meta-analyses could be done for serum creatinine, creatinine clearance, or cystatin C., Conclusions: The overall evidence for an association between renal dysfunction and cognitive impairment or dementia is modest. Evidence suggests that albuminuria is associated with higher odds of developing cognitive impairment or dementia., (© 2016 American Academy of Neurology.)

Background: Dementia prevalence is increasing as populations live longer, with no cure and the costs of caring exceeding many other conditions. There is increasing evidence for modifiable risk factors which, if addressed in mid-life, can reduce the risk of developing dementia in later life. These include physical inactivity, low cognitive activity, mid-life obesity, high blood pressure, and high cholesterol. This study aims to assess the acceptability and feasibility and impact of giving those in mid-life, aged between 40 and 60 years, an individualised dementia risk modification score and profile and access to personalised on-line health information and goal setting in order to support the behaviour change required to reduce such dementia risk. A secondary aim is to understand participants' and practitioners' views of dementia prevention and explore the acceptability and integration of the Innovative Midlife Intervention for Dementia Deterrence (In-MINDD) intervention into daily life and routine practice., Methods/design: In-MINDD is a multi-centre, primary care-based, single-blinded randomised controlled feasibility trial currently being conducted in four European countries (France, Ireland, the Netherlands and the UK). Participants are being recruited from participating general practices. Inclusion criteria will include age between 40 and 60 years; at least one modifiable risk factor for dementia risk (including diabetes, hypertension, obesity, renal dysfunction, current smoker, raised cholesterol, coronary heart disease, current or previous history of depression, self-reported sedentary lifestyle, and self-reported low cognitive activity) access to the Internet. Primary outcome measure will be a change in dementia risk modification score over the timescale of the trial (6 months). A qualitative process evaluation will interview a sample of participants and practitioners about their views on the acceptability and feasibility of the trial and the links between modifiable risk factors and dementia prevention. This work will be underpinned by Normalisation Process Theory., Discussion: This study will explore the feasibility and acceptability of a risk profiler and on-line support environment to help individuals in mid-life assess their risk of developing dementia in later life and to take steps to alleviate that risk by tackling health-related behaviour change. Testing the intervention in a robust and theoretically informed manner will inform the development of a future, full-scale randomised controlled trial., Trial Registration: ISRCTN Registry: ISRCTN 98553005 (DOI: 10.1186/ISRCTN98553005).

Objective: Dementia has a multifactorial etiology, but the importance of individual health and lifestyle related risk factors is often uncertain or based on few studies. The goal of this paper is to identify the major modifiable risk factors for dementia as a first step in developing an effective preventive strategy and promoting healthy late life cognitive functioning., Methods: A mixed-method approach combined findings from a systematic literature review and a Delphi consensus study. The literature search was conducted in PubMed and updated an earlier review by the United States National Institutes of Health from 2010. We reviewed the available evidence from observational epidemiological studies. The online Delphi study asked eight international experts to rank and weigh each risk factor for its importance for dementia prevention., Results: Out of 3127 abstracts, 291 were included in the review. There was good agreement between modifiable risk factors identified in the literature review and risk factors named spontaneously by experts. After triangulation of both methods and re-weighting by experts, strongest support was found for depression, (midlife) hypertension, physical inactivity, diabetes, (midlife) obesity, hyperlipidemia, and smoking, while more research is needed for coronary heart disease, renal dysfunction, diet, and cognitive activity., Conclusions: Findings provide good support for several somatic and lifestyle factors and will be used to inform the design of a new multicenter trial into dementia prevention., (Copyright © 2014 John Wiley & Sons, Ltd.)