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APOE ?4 Modifies Effect of Residential Greenness on Cognitive Function among Older Adults: A Longitudinal Analysis in China.

ABSTRACT: We tested whether the protective effects of residential greenness on cognitive function differ by APOE ?4 status by using the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We calculated Normalized Difference Vegetation Index (NDVI) using 500?m radii around residential addresses to measure greenness, and the Mini-Mental State Examination (MMSE) to assess cognitive function. We dichotomized the participants into APOE non-?4 carriers, and APOE ?4 carriers. We applied the generalized estimating equations (GEE) to examine the association between baseline annual average NDVI, APOE ?4 carrier status, and cognitive impairment. Among 6,994 participants, 19.30% were APOE ?4 carriers. Compared to APOE ?4 non-carriers, the APOE ?4 carriers had a 15% higher odds of cognitive impairment (OR: 1.15, 95% CI: 1.05, 1.26). There was an age difference; the protective effect of residential greenness (the highest vs. lowest quartile) on cognitive impairment was observed among the non-?4 carriers (OR: 0.83, 95% CI: 0.72, 0.95), but not among the ?4 carriers (OR: 1.00, 95% CI: 0.74, 1.34). However, the interaction term between annual average NDVI and APOE ?4 status was not significant (OR: 1.04, 95% CI: 0.97, 1.11). The protective effects of residential greenness on cognitive function differed by APOE ?4 status, which elucidated possible gene-environment interaction mechanisms in which residential greenness may benefit health.

SUBMITTER: Zhu A

PROVIDER: S-EPMC6952401 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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APOE ε4 Modifies Effect of Residential Greenness on Cognitive Function among Older Adults: A Longitudinal Analysis in China.

Zhu Anna A Yan Lijing L Shu Chang C Zeng Yi Y Ji John S JS

Scientific reports 20200109 1

We tested whether the protective effects of residential greenness on cognitive function differ by APOE ε4 status by using the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We calculated Normalized Difference Vegetation Index (NDVI) using 500 m radii around residential addresses to measure greenness, and the Mini-Mental State Examination (MMSE) to assess cognitive function. We dichotomized the participants into APOE non-ε4 carriers, and APOE ε4 carriers. We applied the generalized estima ...[more]

PMID: 31919381

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Project description:ImportanceLiving in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD.ObjectiveTo evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China.Design, setting, and participantsThis analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km2) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020.Main outcomes and measuresLifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level.ResultsAmong 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12 661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels.Conclusions and relevanceIn this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings.

Project description:ObjectiveTo exam the association of cognitive decline with APOE ε4 allele carriage and dietary protein intake and investigate whether there is a gene-diet (GxD) interaction of APOE ε4 allele carriage and dietary protein intake on cognitive decline in a nationwide cohort of older adults.MethodsA cohort study of participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2014. A total of 3029 participants (mean age of 77.0 years, SD = 9.0; 49.3% were women) was enrolled. We genotyped APOE ε4 allele for each participant and calculated the diversity of dietary protein intake (DDPI) by summing up the frequency of intake of the 6 protein-rich foods (meats, fish, eggs, nuts, dairy products, and bean products). We assessed cognitive function using the Mini-Mental State Examination (MMSE). We used ordinal regression model to estimate the independent and joint effects of APOE ε4 carrier and dietary protein intake on cognitive decline, adjusting for potential confounders of age, sex, education, socio-economic status, lifestyles, BMI, and cardiometabolic conditions.ResultsThere was significant association between carrying APOE ε4 allele and faster cognitive decline (Odds ratio: 1.19, 95% CI = 1.00-1.42), independent of potential confounders. While the associations of DDPI and the intake of 6 protein-rich foods with cognitive decline did not reach any statistical significance. We observed significant interactions of APOE ε4 with DDPI and fish intake, at multiple correction-adjusted Ps < 0.05. In those who were APOE ε4 carriers rather than non-carriers, both high DDPI (OR = 0.54, 95% CI: 0.34-0.88) and daily fish intake (OR = 0.43, 95% CI: 0.22-0.78) were significantly associated with slower cognitive decline, respectively. We also found that frequent intake of fish benefits women more than men regarding the mitigating of cognitive decline among APOE ε4 allele carriers (P for interaction = 0.016).ConclusionsThe results of this study support the hypothesis that diversified protein food intake in addition to frequent fish intake may reduce the detrimental effect of APOE ε4 on cognitive health.

Project description:BackgroundExposure to natural vegetation, or greenness, might affect health through several pathways, including increased physical activity and social engagement, improved mental health, and reductions in exposure to air pollution, extreme temperatures, and noise. Few studies of the effects of greenness have focused on Asia, and, to the best of our knowledge, no study has assessed the effect on vulnerable oldest-old populations. We assessed the association between residential greenness and mortality in an older cohort in China.MethodsWe used five waves (February, 2000-October, 2014) of the China Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort representative of the general older population in China. We assessed exposure to greenness through satellite-derived Normalised Difference Vegetation Index (NDVI) values in the 250 m and 1250 m radius around the residential address for each individual included in the study. We calculated contemporaneous NDVI values, cumulative NDVI values, and changes in NDVI from the start of the study over time. The health outcome of the study was all-cause mortality, excluding accidental deaths. Mortality rate ratios were estimated with Cox proportional hazards models, adjusted for age, sex, ethnicity, marital status, geographical region, childhood and adult socioeconomic status, social and leisure activity, smoking status, alcohol consumption, and physical activity.FindingsAmong 23 754 individuals (mean age at baseline 93 years [SD 7·5]) totaling 80 001 person-years, we observed 18 948 deaths during 14 years of follow-up, between June, 2000, and December, 2014. Individuals in the highest quartile of contemporaneous NDVI values had 27% lower mortality than those in the lowest quartile for the 250 m radius (hazard ratio [HR] 0·73, 95% CI 0·70-0·76), and 30% lower mortality for the 1250 m radius (0·70, 0·67-0·74). No clear association was observed for cumulative NDVI measurements and mortality. We did not detect an association between area-level changes in NDVI and mortality.InterpretationOur research suggests that proximity to more green space is associated with increased longevity, which has policy implications for the national blueprint of ecological civilisation and preparation for an ageing society in China.FundingBill & Melinda Gates Foundation, US National Institute on Aging, US National Institute of Health, Natural Science Foundation of China, UN Population Fund, China Social Sciences Foundation, and Hong Kong Research Grants Council.

Project description:BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Project description:BackgroundApolipoprotein E (APOE) ε4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease (AD), while lifestyle factors such as smoking, drinking, diet, and physical activity also have impact on cognition. The goal of the study is to investigate whether the association between lifestyle and cognition varies by APOE genotype among the oldest old.Methods and findingsWe used the cross-sectional data including 6,160 oldest old (aged 80 years old or older) from the genetic substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) which is a national wide cohort study that began in 1998 with follow-up surveys every 2-3 years. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score less than 18. Healthy lifestyle profile was classified into 3 groups by a composite measure including smoking, alcohol consumption, dietary pattern, physical activity, and body weight. APOE genotype was categorized as APOE ε4 carriers versus noncarriers. We examined the associations of cognitive impairment with lifestyle profile and APOE genotype using multivariable logistic regressions, controlling for age, sex, education, marital status, residence, disability, and numbers of chronic conditions. The mean age of our study sample was 90.1 (standard deviation [SD], 7.2) years (range 80-113); 57.6% were women, and 17.5% were APOE ε4 carriers. The mean MMSE score was 21.4 (SD: 9.2), and 25.0% had cognitive impairment. Compared with those with an unhealthy lifestyle, participants with intermediate and healthy lifestyle profiles were associated with 28% (95% confidence interval [CI]: 16%-38%, P < 0.001) and 55% (95% CI: 44%-64%, P < 0.001) lower adjusted odds of cognitive impairment. Carrying the APOE ε4 allele was associated with 17% higher odds (95% CI: 1%-31%, P = 0.042) of being cognitively impaired in the adjusted model. The association between lifestyle profiles and cognitive function did not vary significantly by APOE ε4 genotype (noncarriers: 0.47 [0.37-0.60] healthy versus unhealthy; carriers: 0.33 [0.18-0.58], P for interaction = 0.30). The main limitation was the lifestyle measurements were self-reported and were nonspecific. Generalizability of the findings is another limitation because the study sample was from the oldest old in China, with unique characteristics such as low body weight compared to populations in high-income countries.ConclusionsIn this study, we observed that healthier lifestyle was associated with better cognitive function among the oldest old regardless of APOE genotype. Our findings may inform the cognitive outlook for those oldest old with high genetic risk of cognitive impairment.

Project description:BackgroundThere is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele.ObjectivesWe assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors.MethodsThe Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18-24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends.ResultsAmong 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI -0.1, -0.06) in global cognition across biennial visits among APOE-ε4 positive individuals and a 0.07 SD (95%CI -0.09, -0.05) decline among APOE-ε4 negative individuals. Results for PM2.5, PM10 and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants.ConclusionsThese results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.

Dataset Information

APOE ?4 Modifies Effect of Residential Greenness on Cognitive Function among Older Adults: A Longitudinal Analysis in China.

Publications

APOE ε4 Modifies Effect of Residential Greenness on Cognitive Function among Older Adults: A Longitudinal Analysis in China.

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