RESUMO
BACKGROUND: APOE-e4 is the strongest genetic risk factor for Alzheimer's disease. However, the influence of APOE-e4 on dietary fat intake and cognition has not been investigated. OBJECTIVE: We aim to examine the association of types of dietary fat and their association to cognitive decline among those with and without the APOE-e4 allele. METHODS: The study included 3,360 Chicago Health and Aging Project (CHAP) participants from four Southside Chicago communities. Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE, and diet using a 144-item food frequency questionnaire. APOE genotype was assessed by the hME Sequenom mass-array platform. Longitudinal mixed-effect regression models were used to examine the association of dietary fat and the APOE-e4 allele with cognitive decline, adjusted for age, sex, education, smoking status, and calorie intake. RESULTS: The present study involved 3,360 participants with a mean age of 74 at baseline, 62% African Americans, 63% females, and a mean follow-up of 7.8 years. Among participants with the APOE-e4 risk allele, higher intakes of total and saturated fat (SFA) were associated with a faster decline in global cognition. Among individuals with the APOE-e4 risk allele, a 5% increase in calories from SFA was associated with a 21% faster decline (ß = -0.0197, P = 0.0038). In contrast, a higher intake of long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFA) was associated with a slower rate of decline in global cognition among APOE-e4 carriers. Specifically, for every 1% energy increment from LC-n3 PUFA, the annual rate of global cognitive decline was slower by 0.024 standardized unit (SD 0.010, P = 0.023), about 30.4% slower annual cognitive decline. Higher SFA or other types of dietary fat were not associated with cognitive decline among APOE-e4 non-carriers. CONCLUSIONS: Our study found a significant association between SFA and faster cognitive decline, LC-n3 PUFA and slower cognitive decline among those with the APOE-e4 allele. Our findings suggested that higher intake of SFA might contribute faster cognitive decline in combination with APOE-e4 whereas LC-n3 PUFA might compensate the adverse effects of APOE-e4. The interaction between intakes of different types of dietary fat and APOE-e4 on cognitive function warrants further research.
Assuntos
Alelos , Apolipoproteína E4 , Disfunção Cognitiva , Gorduras na Dieta , Humanos , Feminino , Masculino , Gorduras na Dieta/administração & dosagem , Idoso , Estudos Longitudinais , Disfunção Cognitiva/genética , Disfunção Cognitiva/epidemiologia , Apolipoproteína E4/genética , Fatores de Risco , Negro ou Afro-Americano/genética , Chicago/epidemiologia , Idoso de 80 Anos ou mais , Genótipo , CogniçãoRESUMO
BACKGROUND: Little is known about how depressive symptoms and glial fibrillary acid protein (GFAP) concentrations taken together may influence cognitive functioning. Understanding this relationship may inform strategies for screening and early intervention to decrease the rate of cognitive decline. METHODS: This study sample includes 1 169 participants from the Chicago Health and Aging Project (CHAP), consisting of 60% Black participants and 40% White participants, and 63% female participants and 37% male participants. CHAP is a population-based cohort study of older adults with a mean age of 77 years. Linear mixed-effects regression models tested the main effects of depressive symptoms and GFAP concentrations and their interactions on baseline cognitive function and cognitive decline over time. Models included adjustments for age, race, sex, education, chronic medical conditions, body mass index, smoking status, alcohol use, and their interactions with time. RESULTS: The interaction of depressive symptomology and GFAP (ß = -0.105 [standard error = 0.038], p = .006) on global cognitive function was statistically significant. Participants with depressive symptoms including and above the cutoff and high log of GFAP concentrations had more cognitive decline over time, followed by participants with depressive symptoms below the cutoff and high log of GFAP concentrations, depressive symptom scores including and above the cutoff and low log of GFAP concentrations, and depressive symptom scores below the cutoff and low log of GFAP concentrations. CONCLUSIONS: Depressive symptoms have an additive effect on the association between the log of GFAP and baseline global cognitive function.
Assuntos
Disfunção Cognitiva , Depressão , Humanos , Masculino , Feminino , Idoso , Estudos de Coortes , Depressão/epidemiologia , Depressão/psicologia , Proteína Glial Fibrilar Ácida , Disfunção Cognitiva/diagnóstico , CogniçãoRESUMO
INTRODUCTION: The aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure. METHODS: This study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes. RESULTS: In a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities. DISCUSSION: Promoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.
RESUMO
BACKGROUND: Patients with stroke are at a higher risk of cognitive impairment and Alzheimer's disease dementia. OBJECTIVE: To quantify the role of lifestyle pre-stroke, post-stroke, and changes in lifestyle before and after stroke with cognitive decline in community-dwelling stroke survivors. METHODS: Utilizing data from the Chicago Health and Aging Project, a population-based cohort study, we studied 1,078 individuals with stroke (662 incident and 416 prevalent) who underwent cognitive testing during the study period. A healthy lifestyle score was defined by scoring four behaviors: non-smoking, exercising, being cognitively active, and having a high-quality diet. The global cognitive score was derived from a comprehensive battery of 4 standardized tests. RESULTS: The mean age at incident stroke was 78.2 years, and 60.1% were women. A healthy lifestyle pre-incident stroke was associated with a slower rate of cognitive decline after stroke. Participants with 3-4 healthy lifestyle factors pre-incident stroke had a slower cognitive decline after stroke by 0.046 units/year (95% CI 0.010, 0.083), or 47.7% slower, than participants with 0-1 healthy lifestyle factor. Lifestyle score post-prevalent stroke was not associated with cognitive decline. Changes in lifestyle behaviors from pre- to post-incident stroke were related to cognitive decline after stroke. Individuals who deteriorated their lifestyle quality after stroke had a faster cognitive decline by 0.051 units/year (ß -0.051, 95% CI -0.090, -0.012) than participants with no change in lifestyle score. CONCLUSION: A healthy lifestyle pre-stroke was associated with a slower rate of cognitive decline in stroke survivors, highlighting the importance of primary prevention. After the stroke, changes in lifestyle behaviors may influence the cognitive abilities of older adults as they age.
Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Idoso , Cognição , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Estudos de Coortes , Feminino , Humanos , Vida Independente , Estilo de Vida , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/psicologia , SobreviventesRESUMO
BACKGROUND: African American (AA) adults have about twice the risk of developing dementia compared with white adults. However, evidence on dietary modification in preventing cognitive decline from diverse populations focusing on AA adults is minimal. OBJECTIVES: We aimed to evaluate the association between a plant-based diet and the rate of cognitive decline in a population-based sample of AA and white adults. METHODS: This study consisted of 3337 participants from the Chicago Health and Aging Project (60% AA participants, 64% female). Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Global cognition was assessed using a composite score of 4 individual tests of cognition. We used mixed models to examine the associations of PDI, hPDI, and uPDI with the rates of decline in global cognition, perceptual speed, and episodic memory. Models were adjusted for age, sex, presence of apoE e4 allele, lifestyle factors including education, cognitive activities, smoking status, calorie intake, risk factors for cardiovascular disease, time, and the interaction terms of time × each covariate. RESULTS: AA and white participants had various dietary patterns. Higher hPDI was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AA participants but not white participants. AA study participants in the highest quintile of hPDI had significantly slower rates of global cognitive decline (ß: 0.0183 ± 0.0086; P = 0.032), perceptual speed (ß: 0.0179 ± 0.0088; P = 0.04), and episodic memory (ß: 0.0163 ± 0.0118; P = 0.04) than individuals in the lowest quintile of hPDI. There were no associations of either PDI or uPDI with the rate of cognitive decline in either racial group. CONCLUSIONS: A healthy plant-based diet was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AA adults.
Assuntos
Negro ou Afro-Americano , Disfunção Cognitiva , Idoso , Apolipoproteínas E , Estudos de Coortes , Dieta , Dieta Vegetariana , HumanosRESUMO
OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer's dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer's dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer's dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer's dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). CONCLUSION: A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer's dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.
Assuntos
Doença de Alzheimer , Idoso , Estudos de Coortes , Feminino , Estilo de Vida Saudável , Humanos , Expectativa de Vida , Estilo de Vida , Masculino , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: We investigated the role of genetic risk and adherence to lifestyle factors on cognitive decline in African Americans and European Americans. METHODS: Using data from the Chicago Health and Aging Project (1993-2012; n = 3874), we defined the genetic risk based on presence of apolipoprotein E (APOE) ε4$\varepsilon 4$ allele and determined a healthy lifestyle using a scoring of five factors: non-smoking, exercising, being cognitively active, having a high-quality diet, and limiting alcohol use. We used linear mixed-effects models to estimate cognitive decline by genetic risk and lifestyle score. RESULTS: APOE ε4$\varepsilon 4$ allele was associated with faster cognitive decline in both races. However, within APOE ε4$\varepsilon 4$ carriers, adherence to a healthy lifestyle (eg., 4 to 5 healthy factors) was associated with a slower cognitive decline by 0.023 (95% confidence interval [CI] 0.004, 0.042) units/year in African Americans and 0.044 (95% CI 0.008, 0.080) units/year in European Americans. DISCUSSION: A healthy lifestyle was associated with a slower cognitive decline in African and European Americans.
Assuntos
Negro ou Afro-Americano , Disfunção Cognitiva , Negro ou Afro-Americano/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Disfunção Cognitiva/genética , Estilo de Vida Saudável , Humanos , Fatores de RiscoRESUMO
Adherence to a healthy lifestyle-characterized by abstaining from smoking, being physically and cognitively active, having a high-quality diet, and limiting alcohol use-is associated with slower cognitive decline in older adults, but whether this relationship extends to persons with a genetic predisposition (e.g., carriers of the ε4 allele of the apolipoprotein E gene (APOE*E4)) remains uncertain. Using data from a population-based study, the Chicago Health and Aging Project (Chicago, Illinois), we followed 3,886 individuals who underwent regular clinical and cognitive assessments from 1993 to 2012. Of 3,886 older adults, 1,269 (32.7%) were APOE*E4 carriers. Compared with noncarriers, APOE*E4 carriers had faster cognitive decline (ß = -0.027 units/year, 95% confidence interval (CI): -0.032, -0.023). In contrast, persons with 2-3 and 4-5 healthy lifestyle factors had slower cognitive decline (ß = 0.008 units/year (95% CI: 0.002, 0.014) and ß = 0.019 units/year (95% CI: 0.011, 0.026), respectively) compared with those with 0-1 factor. In analyses stratified by APOE*E4 status, adherence to a healthy lifestyle (e.g., 4-5 factors vs. 0-1 factors) was associated with a slower rate of cognitive decline in both APOE*E4 carriers (ß = 0.029, 95% CI: 0.013, 0.045) and noncarriers (ß = 0.013, 95% CI: 0.005, 0.022). These results underscore the impact of a healthy lifestyle on cognition, particularly among persons with a genetic predisposition, who are more vulnerable to cognitive decline as they age.
Assuntos
Envelhecimento/genética , Envelhecimento/psicologia , Apolipoproteína E4/genética , Disfunção Cognitiva/genética , Estilo de Vida Saudável , Idoso , Alelos , Chicago/epidemiologia , Disfunção Cognitiva/epidemiologia , Inquéritos sobre Dietas , Feminino , Predisposição Genética para Doença/genética , Avaliação Geriátrica , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
RESUMO
INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
Assuntos
Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Negro ou Afro-Americano/genética , Loci Gênicos , Proteínas dos Microfilamentos/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Polimorfismo de Nucleotídeo Único , Simportadores/genética , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Complicações do Diabetes/etnologia , Complicações do Diabetes/genética , Escolaridade , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Prevalência , Fumar/etnologia , Fumar/genéticaRESUMO
BACKGROUND: The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. METHODS AND RESULTS: We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). CONCLUSIONS: We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Modelos Genéticos , Grupos Raciais , Acidente Vascular Cerebral , Substância Branca , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos/genética , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)). CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.
Assuntos
Apolipoproteínas E/genética , Fatores de Transcrição Forkhead/genética , Longevidade/genética , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular/genética , Estudos de Coortes , Feminino , Proteína Forkhead Box O3 , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Ácido Caínico/genética , Receptor de GluK2 CainatoRESUMO
BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.
Assuntos
Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Mortalidade , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: To examine the association of perceived stress with magnetic resonance imaging (MRI) markers of subclinical cerebrovascular disease in an elderly cohort. METHODS: Using a cross-sectional study of a community-based cohort in Chicago, 571 adults (57% women; 58.1% African American; 41.9% non-Hispanic white; mean [SD] age: 79.8 [5.9] years) from the Chicago Health and Aging Project, an epidemiologic study of aging, completed questionnaires on perceived stress, medical history, and demographics as part of an in-home assessment and 5 years later underwent a clinical neurologic examination and MRI of the brain. Outcome measures were volumetric MRI assessments of white matter hyperintensity volume (WMHV), total brain volume (TBV), and cerebral infarction. RESULTS: Stress was measured with six items from the Perceived Stress Scale (PSS); item responses, ranging from never (0) to often (3), were summed to create an overall stress score (mean [SD]: 4.9 [3.3]; range: 0-18). Most participants had some evidence of vascular disease on MRI, with 153 participants (26.8%) having infarctions. In separate linear and logistic regression models adjusted for age, sex, education, race, and time between stress assessment and MRI, each one-point increase in PSS score was associated with significantly lower TBV (coefficient = -0.111, SE = 0.049, t[563] = -2.28, p = 0.023) and 7% greater odds of infarction (odds ratio: 1.07; 95% confidence interval: 1.01, 1.13; Wald χ(2)[1] = 4.90; p = 0.027). PSS scores were unrelated to WMHV. Results were unchanged with further adjustment for smoking, body mass index, physical activity, history of heart disease, stroke, diabetes, hypertension, depressive symptoms, and dementia. CONCLUSIONS: Greater perceived stress was significantly and independently associated with cerebral infarction and lower brain volume assessed 5 years later in this elderly cohort.
Assuntos
Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Infarto Cerebral/psicologia , Transtornos Cerebrovasculares/patologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Fibras Nervosas Mielinizadas/patologia , Neuroimagem , Autorrelato , Estresse Psicológico/patologiaRESUMO
OBJECTIVE: Exposure to acute and chronic stress can affect learning and memory, but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample. METHODS: Participants included 6207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging Project. Two to five in-home assessments were completed over an average of 6.8 years of follow-up and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a six-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment. RESULTS: Mixed-effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B = -0.0379, standard error = 0.0025, p < .001) and a faster rate of cognitive decline (stress × time interaction: B = -0.0015, standard error = 0.0004, p < .001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age, or education. CONCLUSIONS: Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults 65 years and older.
Assuntos
Transtornos Cognitivos/etiologia , Estresse Psicológico/complicações , Idoso , População Negra/estatística & dados numéricos , Chicago/epidemiologia , Transtornos Cognitivos/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , População Branca/estatística & dados numéricosRESUMO
Recent genome-wide association studies have identified a number of susceptibility loci for Alzheimer disease (AD). To understand the functional consequences and potential interactions of the associated loci, we explored large-scale data sets interrogating the human genome for evidence of positive natural selection. Our findings provide significant evidence for signatures of recent positive selection acting on several haplotypes carrying AD susceptibility alleles; interestingly, the genes found in these selected haplotypes can be assembled, independently, into a molecular complex via a protein-protein interaction (PPI) network approach. These results suggest a possible coevolution of genes encoding physically-interacting proteins that underlie AD susceptibility and are coexpressed in different tissues. In particular, PICALM, BIN1, CD2AP, and EPHA1 are interconnected through multiple interacting proteins and appear to have coordinated evidence of selection in the same human population, suggesting that they may be involved in the execution of a shared molecular function. This observation may be AD-specific, as the 12 loci associated with Parkinson disease do not demonstrate excess evidence of natural selection. The context for selection is probably unrelated to AD itself; it is likely that these genes interact in another context, such as in immune cells, where we observe cis-regulatory effects at several of the selected AD loci.
Assuntos
Doença de Alzheimer/genética , Loci Gênicos , Seleção Genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Idade de Início , Proteínas do Citoesqueleto/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Proteínas Monoméricas de Montagem de Clatrina/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas/genética , Receptor EphA1/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Selective attrition may introduce bias into analyses of the determinants of cognitive decline. This is a concern especially for risk factors, such as smoking, that strongly influence mortality and dropout. Using inverse-probability-of-attrition weights, we examined the influence of selective attrition on the estimated association of current smoking (vs. never smoking) with cognitive decline. METHODS: Chicago Health and Aging Project participants (n = 3713), aged 65-109 years, who were current smokers or never- smokers, underwent cognitive assessments up to 5 times at 3-year interval. We used pooled logistic regression to fit predictive models of attrition due to death or study dropout across the follow-up waves. With these models, we computed inverse-probability-of-attrition weights for each observation. We fit unweighted and weighted, multivariable-adjusted generalized-estimating-equation models, contrasting rates of change in cognitive scores in current versus never-smokers. Estimates are expressed as rates of change in z score per decade. RESULTS: During the 12 years of follow-up, smokers had higher mortality than never-smokers (hazard ratio = 1.93 [95% confidence interval = 1.67 to 2.23]). Higher previous cognitive score was associated with increased likelihood of survival and continued participation. In unweighted analyses, current smokers' cognitive scores declined 0.11 standard units per decade more rapidly than never-smokers' (95% CI = -0.20 to -0.02). Weighting to account for attrition yielded estimates that were 56% to 86% larger, with smokers' estimated 10-year rate of decline up to 0.20 units faster than never-smokers' (95% CI = -0.36 to -0.04). CONCLUSIONS: Estimates of smoking's effects on cognitive decline may be underestimated due to differential attrition. Analyses that weight for the inverse probability of attrition help compensate for this attrition.
Assuntos
Viés , Transtornos Cognitivos/etiologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Fumar/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Cadeias de Markov , Modelos Estatísticos , Fatores de Risco , Fumar/epidemiologia , Fumar/mortalidadeRESUMO
Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.
Assuntos
Envelhecimento/genética , Longevidade/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , HumanosRESUMO
Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age-specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community-based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.
Assuntos
Doença de Alzheimer/epidemiologia , Transtornos Cognitivos/epidemiologia , Planejamento em Saúde Comunitária/tendências , Demência/epidemiologia , Fatores Etários , Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Estudos de Coortes , Planejamento em Saúde Comunitária/métodos , Demência/diagnóstico , Humanos , Incidência , Prevalência , Características de Residência , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: B-vitamin deficiencies have been associated with depression; however, there is very little prospective evidence from population-based studies of older adults. OBJECTIVE: We examined whether dietary intakes of vitamins B-6, folate, or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults. DESIGN: The study sample consisted of 3503 adults from the Chicago Health and Aging project, an ongoing, population-based, biracial (59% African American) study in adults aged > or =65 y. Dietary assessment was made by food-frequency questionnaire. Incident depression was measured by the presence of > or =4 depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale. RESULTS: The logistic regression models, which used generalized estimating equations, showed that higher total intakes, which included supplementation, of vitamins B-6 and B-12 were associated with a decreased likelihood of incident depression for up to 12 y of follow-up, after adjustment for age, sex, race, education, income, and antidepressant medication use. For example, each 10 additional milligrams of vitamin B-6 and 10 additional micrograms of vitamin B-12 were associated with 2% lower odds of depressive symptoms per year. There was no association between depressive symptoms and food intakes of these vitamins or folate. These associations remained after adjustment for smoking, alcohol use, widowhood, caregiving status, cognitive function, physical disability, and medical conditions. CONCLUSION: Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults.