Early-life Education Research Articles

Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence

BackgroundDementia and cognitive impairment can be attributed to genetic and modifiable factors. Considerable evidence emerged in modifiable factors and urgently requires standardized evaluation. We conducted an umbrella review to evaluate the strength and validity of the existing evidence. MethodsWe searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors. For each association, we analyzed the summary effect size, 95 % confidence interval, 95 % prediction interval, heterogeneity, small study effect and excess significance bias. Mendelian randomization studies were descriptively reviewed further exploring the causality of the associations. ResultsIn total, 12,015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, BMI, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for that of midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified causal relationships of education and plasma glucose with Alzheimer's disease. LimitationsLow quality of the studies included. ConclusionsModifiable risk factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Our results support a valuable rationale for future experimental designs to establish further evidence for the associations in larger populations.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.

Do Personality Traits Influence the Association Between Depression and Dementia in Old Age?

Depression and personality traits are independent predictors of dementia or cognitive impairment. Despite the well-established relationship between these two psychosocial factors and dementia, no research has been documented on how personality traits can influence dementia in older adults exhibiting depressive symptoms. This study explores the influence of personality traits on the association between change in depression and dementia in old age. A population-based longitudinal cohort study involving two waves of data collected 5 years apart, containing 2210 American older adults, from the National Social Life, Health, and Aging Project to explore if personality traits influence how change in depression predicts the development of dementia. We assessed these relationships while adjusting for sociodemographic characteristics. Change in depression increased the likelihood of dementia at T2 by 4.2% (AOR = 1.04, p = 0.019) in the co-variate adjusted model. Personality traits, overall, did not influence how depression predicts the development of dementia. However, agreeableness individually nullified the effect of depression on the development of dementia, whereas extraversion was the only personality trait that significantly predicted dementia. Prosocial behaviors should be promoted in old age as these appear to be protective. In addition, early life education and a strong social support can keep the depression–dementia spectrum at bay in old age.

Trajectories of K-12 Schools and Demographic Differences: Evidence From 2017 Life History Mail Survey

Besides information about the highest degree, little information about early-life education is available in most population surveys. This study identified the trajectories of K-12 education history among older adults in the Health and Retirement Study born between 1930 and 1960, and examined the associations with demographic variables. Drawing on 2017 Spring and Fall Life History Mail Survey (LHMS; n = 3,206), we used sequence analysis to determine and classify trajectories of school types across the education history. We identified five trajectories: 1) always private school with White students, 2) always public school with White students, 3) always public school with Non-White students, 4) mostly private school with Non-White students, and 5) no report of school types. The trajectories showed that changes in school type (i.e. private to public) often happened in grade 9. Changes rarely happened across race/ethnicity groups (i.e. mostly White to mostly non-White). We used multinomial logistic regression to examine the relationship between demographic variables and education trajectories. We found that compared to Black participants, White participants were significantly less likely to be in mostly Non-White schools (public and private schools, p<0.001). The 1940s and 1950s cohort were more likely to join mostly White private schools than the 1930s cohort (odds ratio: 1.70 for 1940s and 1.62 for 1950s separately, p<0.005). Our findings illustrate a novel application of sequence analysis with life history data, as well as new evidence on recial segregation in early-life education within the last century.

Effects of education and occupational status on incident dementia: A COSMIC collaborative cohort study

AbstractBackgroundEducation and occupational status are expected to protect against dementia, but the research findings have been inconsistent. This project aimed to examine 1) the unique contributions of education and occupational status to incident dementia, and 2) the mediating effects of occupational status on the association between education and dementia across diverse cohorts.MethodEducation and occupational status were harmonized as binary variables (education: ‘High school completion or above’ vs. ‘Less than high school completion; occupational status: ‘Mid to high status’ vs. ‘Low status’) due to the potential threshold effects and availability across datasets. Clinical diagnosis of dementia was used as an outcome. Using a Coordinated Analysis with 9 international datasets from 7 countries over 4 continents (Table 1; Australia, Germany, Italy, South Korea, Spain, and USA), the Cox proportional hazard regression model was applied to each dataset with participants’ age as the reference point, followed by meta‐analysis to provide the weighted summary effect sizes. Mediation analysis was conducted using the causal mediation approach with survival data (VanderWeele, 2011).ResultWe used data from 10,203 participants whose baseline age ranged from 58 to 103 years. Higher levels of education and occupational status were independently associated with decreased risk of incident dementia (Table 2; HR=0.70, 95% CI=[0.54, 0.92] for education; HR=0.79, HR=[0.66, 0.94] for occupational status). Heterogeneity across datasets was moderate for the education model (I 2=37%) and low for the occupation model (I 2= 0%). For the mediation analysis, the indirect effect was marginally significant (HR=0.94, 95% CI=[0.87, 1.00]) and 12% of the effect of education was mediated by occupational status.ConclusionUsing datasets from wide geographical regions, we found that both early life education and adulthood occupational status were independently predictive of incident dementia. Occupational status showed a weak mediating effect on the association between education and dementia. This finding suggests the importance of dementia prevention efforts in any stage of life course. Policy needs to prioritize early life education (possibly up to secondary education) and also target individuals with low occupational status to deliver dementia prevention and intervention.

What do young Australian adults know about modifiable risk factors for dementia?

BackgroundThere are well established modifiable risk factors for late-life dementia. These risk factors account for over 30% of population attributable dementia risk and accrue over the lifespan. Young adults have the greatest potential to reduce their own risk for dementia. This study aimed to investigate what young Australian adults know about dementia and its risk factors, and further, how they estimated these risks.MethodsAn online survey promoted through various social media platforms was completed by 604 young Australian adults aged 18–44 years of age.ResultsSeventy percent of participants had a limited understanding of dementia (identifying cognitive or functional impairment), 25% had a good understanding, with 5% having no understanding. Twenty percent of respondents thought there were no modifiable risk factors for dementia. Less the half of participants agreed with two of the nine established dementia risk factors (hearing loss in midlife and education in early life), with over half of participants agreeing to the remaining seven risk factors. Females consistently judged the risks conferred by the nine established dementia risk factors to be higher than males. Those who were lonely judged the dementia risk conferred by loneliness to be higher than those who were not lonely; and smokers judged the dementia risk conferred by smoking to be less than non-smokers.ConclusionYoung adults have the greatest potential to change their dementia risk, and these findings show that there are important gaps in knowledge of dementia and its risk factors in this group.

Association Between Components of Cognitive Reserve and Serum BDNF in Healthy Older Adults

Background: The brain-derived neurotrophic factor (BDNF) protein has been shown to have a prominent role in neuron survival, growth, and function in experimental models, and the BDNF Val66Met polymorphism which regulates its expression has been linked to resilience toward the effects of aging on cognition. Cognitively stimulating activity is linked to both increased levels of BDNF in the brain, and protection against age-related cognitive decline. The aim of this study was to investigate the associations between serum BDNF levels, the BDNF Val66Met genotype, and components of cognitive reserve in early and mid-life, measured with the Lifetime of Experiences Questionnaire (LEQ).Methods: Serum BDNF levels were measured cross-sectionally in 156 participants from the Tasmanian Healthy Brain Project (THBP) cohort, a study examining the potential benefits of older adults engaging in a university-level education intervention. Multiple linear regression was used to estimate serum BDNF’s association with age, education, gender, BDNF Val66Met genotype, later-life university-level study, and cognitively stimulating activities measured by the LEQ.Results: Serum BDNF in older adults was associated with early life education and training, increasing 0.007 log(pg/ml) [95%CI 0.001, 0.012] per unit on the LEQ subscale. Conversely, education and training in mid-life were associated with a −0.007 log(pg/ml) [−0.012, −0.001] decrease per unit on the LEQ subscale. Serum BDNF decreased with age (−0.008 log(pg/ml) [−0.015, −0.001] per year), and male gender (−0.109 log(pg/ml) [−0.203, −0.015]), but mean differences between the BDNF Val66Met polymorphisms were not significant (p = 0.066). All effect sizes were small, with mid-life education and training having the largest effect size ( = 0.044).Conclusion: Education in both early and mid-life explained small but significant amounts of variance in serum BDNF levels, more than age or gender. These effects were opposed and independent, suggesting that education at different stages of life may be associated with different cognitive and neural demands. Education at different stages of life may be important covariates when estimating associations between other exposures and serum BDNF.

Early- to Late-Life Environmental Factors and Late-Life Global Cognition: The SONIC study

Life environment across the life course—such as engagement in late-life leisure activity (LA), primary occupation, and early-life education—have been reported to be associated with better late-life cognitive outcomes. However, few studies have included all these factors from the past to the present due to the time-consuming procedure to measure all factors. This study examined (1) whether late-life LA is associated with better late-life cognition, after considering other life environments and (2) whether occupation, education, and childhood intelligence quotient have indirect effects on the late-life cognition through late-life LA. We used baseline data from the groups of 70- and 80-year-olds in the SONIC study (N = 1721 ). Global cognition was measured using the Montreal Cognitive Assessment. As for LA, participants were asked for yes/no answers to questions regarding their engagement in 158 activities. A latent factor representing LA was used in the analyses. We retrospectively evaluated the complexity of work with data, people, and things. As early-life environments, education and language and arithmetic abilities during elementary school were included in the analyses. Age and gender were controlled. A structural equation model showed that late-life LA was significantly associated with higher global cognition, even after controlling for all past factors (RMSEA = .050, GFI = .973, AGFI = .947). Sobel tests showed significant indirect effects of occupation, education, and childhood abilities on cognitive function. Results were robust across age and gender. It is suggested that engagement in LA explains individual differences in late-life cognitive function.

Education in early life markedly reduces the probability of cognitive impairment in later life in Colombia

The objective of this study was to investigate associations between education in early life and cognitive impairment in later life in Colombia. Participants were community-dwelling adults aged 60 years or older from the National Study of Health, Wellbeing and Ageing. Trained interviewers administered a shorter version of the mini-mental state examination. Cognitive impairment was defined as the lowest tertile in the main analysis and as a score of 12 or less out of 19 in the sensitivity analysis. Logistic regression models were adjusted for education, other early life characteristics, and later life characteristics. The prevalence of cognitive impairment was 17.93% in the main analysis (n = 16,505). Compared with participants with no education, the fully adjusted odds ratio for cognitive impairment was 0.57 (95% confidence interval: 0.52, 0.63) in those with some primary education and 0.29 (95% confidence interval: 0.25, 0.34) in those with some secondary education or more. The population attributable fraction for education suggests that at least 10% of cases of cognitive impairment would be eliminated if all children received an education. Similar results were observed in the sensitivity analysis (n = 20,174). This study suggests that education in early life markedly reduces the probability of cognitive impairment in late life in Colombia.

Subjective Cognitive Decline, Cognitive Reserve Indicators, and the Incidence of Dementia

ObjectiveBoth cognitive reserve and subjective cognitive decline are closely related to the risk of dementia. We investigated whether cognitive reserve can modify the risk of dementia developing from subjective cognitive decline. DesignLongitudinal population-based study. Setting and ParticipantsThe prospective study analyzed data from 2099 participants aged 65 or over from the Cognitive Function and Ageing Study–Wales (CFAS-Wales). MethodsDementia was ascertained through the comprehensive judgment symptoms of geriatric mental state automated geriatric examination for computer assisted taxonomy (GMS-AGECAT). Subjective cognitive decline was evaluated by 2 questions in the baseline interview. Cognitive reserve indicators were derived from 3 previously identified factors: early life education, mid-life occupational complexity, and late-life cognitive activities. We used logistic regression models to estimate dementia risk in relation to subjective cognitive decline and indicators of cognitive reserve. The interaction between subjective cognitive decline and cognitive reserve were evaluated by additive and multiplicative scales. ResultsBaseline subjective cognitive decline and low cognitive reserve significantly increased the risk of dementia, after 2 years of follow-up. There was an additive interaction between subjective cognitive decline and cognitive reserve [the relative excess risk due to interaction = −0.63, 95% confidence interval (CI) = −0.89 to −0.36, P for additive interaction <0.001]. There was no multiplicative interaction between subjective cognitive decline and cognitive reserve indicator (P = .138). Statistically significant association between subjective cognitive decline and dementia was found only in the low-level and medium-level cognitive reserve group (OR = 3.78, 95% CI = 1.50–9.55 and OR = 3.64, 95% CI = 1.09–12.2, respectively), but not in the high-level groups. Conclusion and ImplicationsCognitive reserve attenuated subjective cognitive decline associated risk of developing dementia. This finding suggests the need for greater emphasis on detecting prodromal dementia when older patients having lower cognitive reserve present with subjective cognitive decline.

Early-life education may help bolster declarative memory in old age, especially for women

ABSTRACT Although declarative memory declines with age, sex and education might moderate these weaknesses. We investigated effects of sex and education on nonverbal declarative (recognition) memory in 704 older adults (aged 58–98, 0–17 years of education). Items were drawings of real and made-up objects. Age negatively impacted declarative memory, though this age effect was moderated by sex and object-type: it was steeper for males than females, but only for real objects. Education was positively associated with memory, but also interacted with sex and object-type: education benefited women more than men (countering the age effects, especially for women), and remembering real more than made-up objects. The findings suggest that nonverbal memory in older adults is associated negatively with age but positively with education; both effects are modulated by sex, and by whether learning relates to preexisting or new information. The study suggests downstream benefits from education, especially for girls.

Adult development and aging in historical context.

Human functioning and development are shaped by sociocultural contexts and by the historical changes that occur in these contexts. Over the last century, sociocultural changes such as increases in early life education have profoundly reshaped normative developmental sequences. In this article, we first briefly review how history-graded changes have influenced levels of objective performance and subjective evaluations among older adults and conclude that old age in countries such as the United States and Germany is getting younger, both on behavioral measures and in people's own perception. Second, we put these findings in a larger perspective and note some of the "presumed" causes driving historical change. Third, we identify key aspects of change that need to be further described, including history-graded change in (a) the formative role of experiences made across adulthood; (b) within-person trajectories of adult development and aging, including rates of change, patterns of variation, and causal influence; (c) the structure of very old age and the end of life; and (d) what may be expected in the forthcoming decades. We suggest a number of reasons why the rosy picture of historical change obtained for older adults over the last century may not necessarily continue in the future. In a final step, we outline promising methods that might be used to discover and test mechanisms driving history-graded changes, and to inform projection and optimization of functioning and development in future generations of older adults. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cortical thickness and its associations with age, total cognition and education across the adult lifespan.

Early-life education (years of schooling) has been investigated in regards to cognition, health outcomes and mortality. It has been shown to confer cognitive reserve that might lessen the impact of brain pathology and its impact on cognitive and motor functioning in a variety of neurodegenerative diseases and, for instance, to influence electrical activity [Begum, T., Reza, F., Ahmed, I., & Abdullah, J. M. (2014). Influence of education level on design-induced N170 and P300 components of event related potentials in the human brain. J Integr Neurosci, 13(1), 71–88. doi:10.1142/S0219635214500058]. On the other hand, demonstrations of a direct association between education and brain-structural measures have been more equivocal and scant. The current study sought to identify univariate cortical-thickness patterns underlying education and general intelligence after adjusting for age, gender and possible in-scanner movement in 353 individuals aged 40 to 80. We followed up this idea with multivariate analyses as well. For univariate analyses, our analyses yielded no robust associations between education and general intelligence beyond confounding effects of gender, age and extraneous in-scanner movement. A subsequent multivariate analyses showed a relationship between education and regional cortical thickness with a robust pattern of negative as well as positive loadings in several right-sided brain areas, speaking to a subtle but robust distributed effect of education on cortical thickness. Cortical thickness variance that is the residual of this education-related pattern was shown to be positively associated with age and extraneous in-scanner movement. Our study thus presents a complex picture of the association of education with regional cortical thickness: education was associated with a distributed brain-wide pattern of positive as well as negative loadings with unaccounted residuals being larger for older participants. Focal regional associations beyond demographic and age covariates were not identified.

Preventing Covert Brain Infarct-Related Cognitive Impairment and Dementia.

Covert brain infarcts (CBIs) are five times more prevalent than symptomatic brain infarcts. CBIs are associated with cognitive impairment and therefore may be a target for preventing cognitive decline and dementia. This review focuses on strategies for preventing CBI-related cognitive impairment, either by preventing incident or recurrent CBI or by enhancing cognitive reserve. CBIs begin to become prevalent during midlife and are highly prevalent in later life. The distribution of vascular pathologies of CBI differs from those that cause symptomatic stroke; therefore, preventive treatments may need to differ as well. Only a few randomized clinical trials have provided data on CBI prevention, without conclusive results. Limited data suggest that higher early-life education, hypothesized to enhance cognitive reserve, can protect the brain from effects of CBI.

Occupational Patterns of Structural Brain Health: Independent Contributions Beyond Education, Gender, Intelligence, and Age.

Occupational activity represents a large percentage of people’s daily activity and thus likely is as impactful for people’s general and cognitive health as other lifestyle components such as leisure activity, sleep, diet, and exercise. Different occupations, however, require different skills, abilities, activities, credentials, work styles, etc., constituting a rich multidimensional formative exposure with likely consequences for brain development over the lifespan. In the current study, we were interested in how different occupations with their different attributes relate to five variables: structural brain health, duration of early-life education, gender, IQ, and age, although the main focus was the relationship to brain health. To this end, we used the Occupation Information Network (O∗NET), which provides quantification of occupations along 246 items. Occupational patterns with different loadings for these 246 items were derived from 277 community-dwelling adults, ranging in age from 40 to 80, based upon the five subject measures. We found significant patterns underlying four of our variables of interest, with gender and education predictably showing the most numerous and strongest associations, while brain health and intelligence showed weaker associations, and age did not manifest any associations. For the occupational pattern associated with brain health, we found mainly positive associations on items pertaining to rigorous problem-solving, leadership, responsibility, and information processing. We emphasize that the findings are correlational and cannot establish causation. Future extensions of this work will assess the influence of occupation on future cognitive brain status and cognitive performance.

Maternal Education in Early Life and Risk of Metabolic Syndrome in Young Adult American Females and Males: Disentangling Life Course Processes Through Causal Models.

Maternal education in a child's early life may directly affect the child's adult cardiometabolic health, but this is difficult to disentangle from biological, social, and behavioral life course processes that are associated with maternal education. These processes may also differ between males and females. Using data from the National Longitudinal Study of Adolescent to Adult Health (1995-2009) (N = 4,026 females and 3,192 males), we estimated sex-stratified associations between maternal attainment of less than high school (<HS), high school diploma (HS), or college degree (CD) at the respondent's birth and respondent's risk of metabolic syndrome (MetS); we used marginal structural models (MSM) to account for the influence of major life course risk factors, such as childhood maltreatment, adolescent overweight, adult education, household income, smoking, and physical activity, in mediating associations between maternal education and offspring MetS risk. Each higher level of maternal education was associated with a 36% (Relative Risk = 0.64 [95% Confidence Interval (CI): 0.50-0.82]) reduced risk of MetS among females, but only 19% (RR = 0.81 [95% CI: 0.64-1.01]) reduction among males (P-value interaction < 0.05). Stronger inverse associations were also observed for waist circumference and glycated hemoglobin (HbA1c) among females compared with males (-5 cm vs. -2.4 cm and -1.5% vs. -1.0%, respectively). High maternal education in early life was associated with a lower risk of MetS in young adulthood even after accounting for life course risk factors, particularly among females. Results were robust to altered model specifications.

The positive impacts of early-life education on cognition, leisure activity, and brain structure in healthy aging.

Education in people’s early lives are positively related to their cognitive function, but its modulating effects on detailed cognition domains, its interaction with leisure activities and the associated brain changes have yet to be investigated. This report used data from 659 cognitively normal community dwelling elderly who completed neuropsychological tests, leisure activities measurement, and 78 of them underwent structural and diffusion MRI scans. We found that: (i) the highly educated elderly had a better cognitive functioning in multi-domains, higher frequencies of participation in knowledge-related leisure activities, and slower age-related reductions of executive function; (ii) the intellectual and social types of leisure activities mediated the association between education and multiple cognitive domains, including memory, language, attention and executive function; (iii) there was a significant age by education interaction on the gray matter volume of the anterior brain regions and white matter integrity; and (iv) the interaction between age and education affected cognition indirectly through white matter integrity analyzed using structural equation model. Overall, our results revealed that high education in early life served as a protective factor in aging that may help to postpone cognitive and brain reserve decline in cognitively normal aging.

DEMENTIA PREVENTION IN LOW- AND MIDDLE-INCOME COUNTRIES: POPULATION ATTRIBUTABLE FRACTION FOR POTENTIALLY MODIFIABLE RISK FACTORS

Nine potentially modifiable risk factors (less childhood education, hearing loss, smoking, hypertension, obesity, physical inactivity, social isolation, depression, and diabetes) account for 35% of worldwide dementia. Most data to calculate potentially modifiable risk factors comes from high income countries, so the impact of potentially modifiable risk factors in low- to middle-income countries (LMIC) is unknown. Two-thirds of people with dementia live in LMIC and population ageing is projected to result in a significant increase in numbers of people with dementia. We therefore calculated population attributable fractions (PAF) for dementia in the LMIC for which we could obtain population-level data, to identify potential dementia prevention targets in LMIC. We used 10/66 dementia research group cross-sectional surveys of representative populations in India, China and Latin America (Cuba, Dominican Republic, Venezuela, Mexico, Peru and Puerto Rico combined, as risk factor prevalences were similar) which used identical risk factor ascertainment methodology in each country to consider risk factors. 10/66 study representativeness was ensured by pre-defining catchment areas and then approaching all people over 65 years in that catchment area for participation. We used risk factor prevalences from 10/66 and relative risk estimates from previous meta-analyses to calculate PAFs for each risk factor. To account for individuals having overlapping risk factors, we adjusted PAF for communality between risk factors, using these figures to calculate combined PAF figures for India, China and Latin America. The combined PAF for potentially modifiable risk factors for dementia were: 40% in China (N=2162 participants); 41% in India (N=2004) and 56% in Latin America (N=12865). Less childhood education, smoking, hypertension, obesity and diabetes were more common than worldwide estimates across all three regions, leading to higher PAF. There is a large dementia prevention potential in LMIC, specifically India, China and Latin America, which is greater than in high-income countries. Less education in early life, hypertension, hearing loss, obesity and physical inactivity have particularly high PAF and may be initial targets for dementia prevention strategies.

Genetic risk of dementia mitigated by cognitive reserve: A cohort study.

ObjectiveWe investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE‐ε4), a well‐known genetic risk factor for dementia.MethodsWe followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community‐based Swedish National Study on Aging and Care in Kungsholmen (SNAC‐K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE‐ε4 was assessed on multiplicative and additive scales.ResultsAfter an average of 6.3 years (range = 2.1–10.7) of follow‐up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE‐ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE‐ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13–0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15–0.40).InterpretationLifelong engagement in reserve‐enhancing activities attenuates the risk of dementia attributable to APOE‐ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019

Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data

Nine potentially modifiable risk factors (less childhood education, midlife hearing loss, hypertension, and obesity, and later-life smoking, depression, physical inactivity, social isolation, and diabetes) account for 35% of worldwide dementia, but most data to calculate these risk factors come from high-income countries only. We aimed to calculate population attributable fractions (PAFs) for dementia in selected low-income and middle-income countries (LMICs) to identify potential dementia prevention targets in these countries. The study was an analysis of cross-sectional data obtained from the 10/66 Dementia Research surveys of representative populations in India, China, and six Latin America countries (Cuba, Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela), which used identical risk factor ascertainment methods in each country. Between 2004 and 2006 (and between 2007 and 2010 for Puerto Rico), all residents aged 65 years and older in predefined catchment areas were invited to participate in the survey. We used risk factor prevalence estimates from this 10/66 survey data, and relative risk estimates from previous meta-analyses, to calculate PAFs for each risk factor. To account for individuals having overlapping risk factors, we adjusted PAF for communality between risk factors, and used these values to calculate overall weighted PAFs for India, China, and the Latin American sample. The overall weighted PAF for potentially modifiable risk factors for dementia was 39·5% (95% CI 37·5-41·6) in China (n=2162 participants), 41·2% (39·1-43·4) in India (n=2004), and 55·8% (54·9-56·7) in our Latin American sample (n=12 865). Five dementia risk factors were more prevalent in these LMICs than worldwide estimates, leading to higher PAFs for dementia: less childhood education (weighted PAF of 10·8% in China, 13·6% in India, and 10·9% in Latin America vs 7·5% worldwide), smoking (14·7%, 6·4%, and 5·7%, respectively, vs 5·5% worldwide), hypertension (6·4%, 4·0%, and 9·3%, vs 2·0%), obesity (5·6%, 2·9%, and 7·9%, vs 0·8%), and diabetes (1·6%, 1·7%, and 3·2%, vs 1·2%). The dementia prevention potential in India, China, and this sample of Latin American countries is large, and greater than in high-income countries. Less education in early life, hypertension, hearing loss, obesity, and physical inactivity have particularly high PAFs and could be initial targets for dementia prevention strategies. No funding.