Kay Deckers

Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies

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.

Dementia risk in renal dysfunction : a systematic review and meta-analysis of prospective studies

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 m2 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.

Modifiable risk factors for prevention of dementia in midlife, late life and the oldest-old: Validation of the LIBRA index

BACKGROUND Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individuals prevention potential for dementia. OBJECTIVE We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old. METHODS 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individuals LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16). RESULTS In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia. CONCLUSION LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.

Cognitive changes in prevalent and incident cardiovascular disease: a 12-year follow-up in the Maastricht Aging Study (MAAS)

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.

Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis

Aims/Hypothesis Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. Methods Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. Results We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21–1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0–64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. Conclusion/Interpretation This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed.

Lifestyle for Brain Health (LIBRA): a new model for dementia prevention

Modifiable risk factors for dementia were recently identified and compiled in a systematic review. The ‘Lifestyle for Brain Health’ (LIBRA) score, reflecting someones 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.

Lack of associations between modifiable risk factors and dementia in the very old : findings from the Cambridge City over-75s cohort study

ABSTRACT 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 individuals 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.

Obesity and cognitive decline in adults : effect of methodological choices and confounding by age in a longitudinal study

Background and ObjectivesObesity has been associated with increased risk of cognitive impairment or dementia, but recent findings are contradictory, possibly due to methodological differences. The present study tries to clarify these inconsistencies by following the cognitive trajectories of individuals with obesity over 12 years and studying the effect of obesity status (obesity at baseline versus incident obesity at follow-up), chronicity, definition, potential confounding (e.g. age, cardiovascular factors), and non-linear associations.DesignLongitudinal study with 12 years follow-up.SettingCommunity based.Participants1,807 cognitively healthy individuals (aged 24-83) from the Maastricht Aging Study (1992-2004).MeasurementsMemory, executive function and processing speed were assessed at baseline and at 6- and 12-year follow-up. Obesity was defined as having a body mass index (BMI) of ≥ 30.0 kg/m2 or waist circumference (WC) of > 102 cm for men and > 88 cm for women.ResultsAt baseline, 545 persons were obese (BMI: 329 (18%); WC: 494 (27%); both: 278 (15%). They showed faster decline in memory, executive function, and processing speed. Chronic obese showed less widespread impairment than those who regained normal weight. Associations across cognitive domains were weaker for obesity defined by BMI than for WC. At follow-up, 190 developed obesity, and they performed worse on executive function at baseline, but showed less decline compared with participants with normal weight. Yet, age-stratification and post-hoc analyses showed that most of these associations were confounded by age.ConclusionsThis study shows that the association between obesity and cognitive decline was confounded by the effect of age on rate of decline. Future studies should take this into account.

Author response: Dementia risk in renal dysfunction: A systematic review and meta-analysis of prospective studies

We thank Prof. Kawada for the interest in our article,1 and agree that the exact mechanisms underlying the relationship between renal dysfunction and cognitive impairment or dementia are not fully understood. In our article, we discussed several suggested potential mechanisms.1 These might work additively, or synergistically, and include shared vascular risk factors or a direct effect of uremic toxins.1,2

SOCIOECONOMIC INEQUALITIES IN DEMENTIA RISK EXPLAINED BY MODIFIABLE RISK FACTORS: FINDINGS FROM THE ENGLISH LONGITUDINAL STUDY OF AGEING

Background:Differences in dementia risk across the gradient of socioeconomic status exist, but its determinants are not under- stood. Therefore, the aim of this study was to investigate whether differences in socioeconomic status are associated with incident dementia and whether this association is ex- plained by health- and lifestyle-related factors. Methods: 6,346 participants (mean age 1⁄4 64.9, SD 1⁄4 8.6; 55.7% fe- male) were followed up for a maximum of 7 years. Dementia was based on self-reported physician-diagnosed dementia or Alzheimer’s disease at each wave and a score of 3.38 or higher on the shortened version of the IQ-CODE. Socioeco- nomic status was based on wealth defined as household net of debt and included cash, investments, savings and physical wealth. Health- and lifestyle-related factors were captured by a poly-environmental risk score, called the ‘Lifestyle for BRAin Health’ (LIBRA) index. LIBRA consists of a weighted sum score of twelve modifiable risk and protective factors for cognitive decline or dementia. Higher scores indicate higher risk (range -5.9 to +10.3). Cox regression adjusted for age, gender and education and clustering at the household level examined the association between socioeconomic status and time to dementia in a structural equation model including po- tential mediation or effect modification by LIBRA. Results: LIBRA scores decreased with increasing wealth. During a me- dian follow-up of 6.0 years, 192 individuals (3.0%) developed dementia. High socioeconomic status was associated with a decreased dementia risk (highest versus lowest tertile: HR 1⁄4 0.54, 95%CI 1⁄4 0.36-0.79), but this was substantially attenuated after adjusting for differences in LIBRA scores (highest versus lowest tertile: HR 1⁄4 0.77, 95%CI 1⁄4 0.51-1.16). Mediation anal- ysis showed that 58% of the risk difference between the highest and the lowest tertile of wealth was mediated by differences in LIBRA. A one point increase in LIBRA was associated with a 13% increase in dementia risk (HR 1⁄4 1.13, 95%CI 1⁄4 1.07- 1.19) on average (no interaction). Conclusions: Differences in dementia risk between socioeconomic groups can be partly attributed to differences in treatable health- and lifestyle related factors. Future public health campaigns for dementia risk reduction should try hard to reach out to this vulnerable group.