RESUMO
INTRODUCTION: There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. METHODS: This study consists of 1118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline. Stratified analysis by stress level was also conducted to evaluate the associations between each blood biomarker and baseline cognitive function and decline. All models adjusted for age, race, sex, education, time, and their interactions with time. RESULTS: The interaction of stress, NfL concentration, and time was statistically significant on global cognition ( ß = -0.064 [SE = 0.028], p = .023) and on episodic memory ( ß = -0.097 [SE = 0.036], p = .007). CONCLUSIONS: Greater stress level worsens the association between high NfL concentration and cognitive decline. Stress management interventions may be helpful to reduce the rate of cognitive decline in individuals with high concentrations of NfL.
Assuntos
Biomarcadores , Disfunção Cognitiva , Proteína Glial Fibrilar Ácida , Proteínas de Neurofilamentos , Estresse Psicológico , Proteínas tau , Humanos , Feminino , Idoso , Masculino , Biomarcadores/sangue , Estresse Psicológico/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Idoso de 80 Anos ou mais , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Proteína Glial Fibrilar Ácida/sangue , Memória Episódica , Envelhecimento/sangue , Envelhecimento/fisiologia , Chicago , Doença de Alzheimer/sangueRESUMO
OBJECTIVE: This study aimed to examine race and apolipoprotein E-e4 allele (APOE-e4) status differences in the longitudinal associations between loneliness and cognitive decline. METHODS: The study sample is composed of participants ( N = 7696, 64% Black participants and 36% White participants) from the Chicago Health and Aging Project, a population-based cohort study. Mixed-effects regression models were conducted to examine the longitudinal associations between loneliness on global cognitive function and individual tests of cognitive function. Models were also stratified by race and APOE-e4. RESULTS: A greater percentage of Black participants (17%) reported loneliness at baseline visit compared with White participants (12%). Black and White participants who were lonely individuals had a similar rate of decline in global cognitive function at 0.075 (95% confidence interval [CI] = -0.082 to -0.068) standard deviation unit (SDU) per year for Black participants and at 0.075 (95% CI = -0.086 to -0.063) SDU per year for White participants. Lonely participants with APOE-e4 had a higher rate of global cognitive decline at -0.102 (95% CI = -0.115 to -0.088) SDU per year than for lonely participants without APOE-e4 at -0.052 (95% CI = -0.059 to -0.045) SDU per year. CONCLUSIONS: The burden of loneliness and its relation to cognitive decline is higher among participants with APOE-e4 compared with those without APOE-e4. Loneliness is associated with cognitive decline in both Black and White participants.
Assuntos
Apolipoproteína E4 , Disfunção Cognitiva , Humanos , Estudos de Coortes , Apolipoproteína E4/genética , Alelos , Solidão , Apolipoproteínas E/genética , Disfunção Cognitiva/genéticaRESUMO
Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts; 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.
Assuntos
Doenças Neurodegenerativas , Acidente Vascular Cerebral , Idoso , Humanos , Biomarcadores , Infarto Encefálico/epidemiologia , Infarto Encefálico/metabolismo , Estudos de Coortes , Filamentos Intermediários/metabolismo , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/metabolismo , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , IncidênciaRESUMO
BACKGROUND: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline. METHODS: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and physical activity on outcomes: global cognitive function, global cognitive decline, episodic memory, decline in episodic memory, perceptual speed, and decline in perceptual speed. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline. RESULTS: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of high physical activity and neuroticism on baseline global cognitive function (ß = 0.017 (SE = 0.007), p = .010) and on the interaction of neuroticism and high physical activity on baseline episodic memory (ß = 0.020 (SE = .009), p = .021) and on decline in episodic memory over time (ß = -0.003 (SE = .001), p = .039). CONCLUSION: Higher physical activity lessened the association between higher neuroticism and poor cognitive outcomes.
Assuntos
Disfunção Cognitiva , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Neuroticismo , Fatores de Risco , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Cognição , Exercício FísicoRESUMO
INTRODUCTION: This study estimates the prevalence and number of people living with Alzheimer's disease (AD) dementia in 50 US states and 3142 counties. METHODS: We used cognitive data from the Chicago Health and Aging Project, a population-based study, and combined it with the National Center for Health Statistics 2020 bridged-race population estimates to determine the prevalence of AD in adults ≥65 years. RESULTS: A higher prevalence of AD was estimated in the east and southeastern regions of the United States, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). US states with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami-Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York. DISCUSSION: The state- and county-specific estimates could help public health officials develop region-specific strategies for caring for people with AD.
Assuntos
Doença de Alzheimer , Adulto , Humanos , Estados Unidos/epidemiologia , Doença de Alzheimer/epidemiologia , Prevalência , National Center for Health Statistics, U.S. , Florida , EnvelhecimentoRESUMO
INTRODUCTION: To determine the role of vitamin D intake on cognitive decline among Blacks and Whites. METHODS: Using data from the population-based Chicago Health and Aging Project, we studied 2061 Blacks and 1329 Whites with dietary vitamin D data and cognitive testing over 12 years of follow-up. Multivariable linear mixed-effects models were used to determine the association of vitamin D intake with cognitive decline. RESULTS: Vitamin D intake, particularly dietary vitamin D, was associated with a slower rate of decline in cognitive function among Blacks. In Blacks, comparing individuals in the lowest tertile of dietary intake, those in the highest tertile had a slower cognitive decline of 0.017 units/year (95% confidence interval 0.006, 0.027), independently of supplementation use. In Whites, vitamin D intake was not associated with cognitive decline. DISCUSSION: Dietary vitamin D may help to slow the decline in cognitive abilities among Blacks as they age.
Assuntos
Disfunção Cognitiva , Vitamina D , Humanos , Dieta , Suplementos Nutricionais , Vitamina D/administração & dosagem , Vitaminas , Negro ou Afro-Americano , BrancosRESUMO
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
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
This study examined the relationship between walking and cognitive function among Chicago Health and Aging Project participants. Data collection occurred during six 3-year cycles, of which Cycles 4-6 were used for this specific analysis. Information was obtained regarding walking frequency and duration, demographics, chronic conditions, cognitive activities, apolipoprotein E4, physical function, and cognitive function (global and domains). A composite walking measure was developed and categorized as follows: no walking, ≤105 min/week, and >105 min/week. Mixed-effects regression analyses tested associations between walking and global cognitive function, episodic memory, and perceptual speed. The sample consisted of 4,320 participants (African American/Black: 65%; female: 65%; mean education: 13 years; mean age: 75 years). Composite or total walking had a statistically significant association with global cognitive function and perceptual speed, after adjustments were made.
Assuntos
Envelhecimento , Cognição , Idoso , Chicago , Escolaridade , Feminino , Humanos , CaminhadaRESUMO
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: The longitudinal association of the blood biomarkers total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) and cognitive decline is not established. METHODS: Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of t-tau, Nf-L, and GFAP were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, had completed in-home cognitive assessments, and had undergone 1.5T structural magnetic resonance imaging. RESULTS: Higher concentrations of serum biomarkers were associated with the development of clinical AD; especially, the time-specific associations were notable: t-tau 8 to 16 years, and Nf-L and GFAP 4 to 8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years; baseline t-tau > 0.40pg/ml had 30% faster decline, Nf-L > 25.5pg/ml had 110% faster decline, and GFAP > 232pg/ml had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP > 232pg/ml showed 160% faster decline in hippocampal volume compared to those with values < 160pg/ml. Additionally, higher baseline t-tau was associated with faster increase in 3rd ventricular volume, and baseline Nf-L and GFAP were associated with faster decline in cortical thickness. INTERPRETATION: Serum t-tau, Nf-L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer dementia. ANN NEUROL 2020;88:1065-1076.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Proteína Glial Fibrilar Ácida/sangue , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Biomarcadores/sangue , Córtex Cerebral/patologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Diagnóstico Precoce , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Valor Preditivo dos TestesRESUMO
INTRODUCTION: The estimate of people with clinical Alzheimer's disease (AD) and mild cognitive impairment provides an understanding of the disease burden. METHODS: We estimated people with cognitive impairment using a quasibinomial regression model in 10,342 participants with cognitive test scores. RESULTS: The 2020 US Census-adjusted prevalence of clinical AD was 11.3% (95% confidence interval [CI] = 10.7-11.9): 10.0% among non-Hispanic Whites, 14.0% among Hispanics, and 18.6% among non-Hispanic Blacks. We estimate that in 2020, 6.07 (95% CI = 5.75-6.38) million people were living with clinical AD, which increases to 13.85 (95% CI = 12.98-14.74) million in 2060, 423% higher among Hispanics, 192% higher among Blacks, and 63% higher among Whites. However, there are predicted to be more significant increases in later years among those over 85 and women compared to men. DISCUSSION: The number of people with clinical AD will increase as the "baby boom" generation reaches older ages, exerting a strong upward influence on disease burden.
Assuntos
Disfunção Cognitiva/epidemiologia , Etnicidade/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Modelos Estatísticos , PrevalênciaRESUMO
INTRODUCTION: It is unclear whether eating Western diet food components offsets the Mediterranean diet's (MedDiet) potential benefits on cognitive decline. METHODS: The study includes 5001 Chicago Health and Aging Project participants (63% African American, 36% males, 74 ± 6.0 years old), with food frequency questionnaires and ≥ two cognitive assessments over 6.3 ± 2.8 years of follow-up. Mixed-effects models were adjusted for age, sex, education, race, cognitive activities, physical activity, and total calories. RESULTS: Stratified analysis showed a significant effect of higher MedDiet on cognitive decline only with a low Western diet score (highest vs lowest MedDiet tertile: ß = 0.020, P = .002; p trend = 0.002) and not with a high Western diet score (highest vs lowest MedDiet tertile: ß = 0.010, P = .11; p trend = 0.09). CONCLUSION: This prospective study found that high consumption of Western diet components attenuates benefits of the MedDiet on cognition.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Disfunção Cognitiva/prevenção & controle , Dieta Mediterrânea/etnologia , Dieta Ocidental/etnologia , Idoso , Envelhecimento/fisiologia , Chicago , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Exposure to noise might influence risk of Alzheimer's disease (AD) dementia. METHODS: Participants of the Chicago Health and Aging Project (≥65 years) underwent triennial cognitive assessments. For the 5 years preceding each assessment, we estimated 5227 participants' residential level of noise from the community using a spatial prediction model, and estimated associations of noise level with prevalent mild cognitive impairment (MCI) and AD, cognitive performance, and rate of cognitive decline. RESULTS: Among these participants, an increment of 10 A-weighted decibels (dBA) in noise corresponded to 36% and 29% higher odds of prevalent MCI (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.15 to 1.62) and AD (OR = 1.29, 95% CI, 1.08 to 1.55). Noise level was associated with worse global cognitive performance, principally in perceptual speed (-0.09 standard deviation per 10 dBA, 95% CI: -0.16 to -0.03), but not consistently associated with cognitive decline. DISCUSSION: These results join emerging evidence suggesting that noise may influence late-life cognition and risk of dementia.
Assuntos
Cognição/fisiologia , Disfunção Cognitiva/psicologia , Demência/epidemiologia , Ruído/efeitos adversos , Características de Residência , Idoso , Idoso de 80 Anos ou mais , Chicago/epidemiologia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: To examine the association of blood pressure (BP) with incident Alzheimer's disease (AD) dementia. METHODS: This work is based on a longitudinal, cohort study of 18 years, the Chicago Health and Aging Project (CHAP) performed in 2,137 participants (55% black) with systolic BP measured around 8.1 years before incident AD dementia. RESULTS: The association of BP with risk of AD dementia was U-shaped, with the lowest risks of AD dementia near the center of the systolic BP (SBP) and diastolic BP (DBP) distributions, and modestly elevated risk at lower BPs, and greater risk at higher BPs. The degree of U-shape and the range of lowest risk (threshold ranges) varied with antihypertensive medication use and presence of the APOE ε4 allele. The U-shape was most prominent for the subgroup not taking antihypertensive medications and having an APOE ε4 allele. At higher BPs, those having the APOE ε4 allele and not receiving antihypertensive medication were at greater risk of AD dementia than other groups: The risk of incident AD dementia increased by 100% (relative risk [RR] = 2.00; 95% confidence interval [CI] = 1.70, 2.31) for every 10 mm Hg increase in SBP above 140 mm Hg. For DBP, the risk of incident of AD dementia increased by 57% (RR = 1.57; 95% CI = 1.33, 1.86) for every 5 mm Hg increase in DBP above 76 mm Hg. INTERPRETATION: The BP risk of AD dementia association is U-shaped, with elevated risk at lower and higher BPs. People having the APOE ε4 allele and not receiving antihypertensive medication with higher BPs have notably elevated risk of AD dementia. Ann Neurol 2018;83:935-944.
Assuntos
Doença de Alzheimer/genética , Anti-Hipertensivos/uso terapêutico , Apolipoproteína E4/genética , Pressão Sanguínea/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Pressão Sanguínea/genética , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To determine relationships of memory complaints to cognitive function and decline, incident dementia, and neurodegenerative and other neuropathologies, as well as the population-attributable risk for dementia in older black and white persons. METHODS: A total of 4,015 community-based persons (28% black; 74% women; mean baseline age = 78 years) were enrolled in 1 of 4 longitudinal cohort studies, and another 2,937 in a population-based cohort. Memory scores, assessed using 2 questions (5-point Likert scales) were categorized as complaints present or absent. Global cognition and 5 cognitive domains were derived from annual neuropsychological tests. Dementia was assessed from these tests and additional data. Neuropathologic data were available for 1,350 deceased subjects with brain autopsies. Regression and mixed effects models were used to examine relationships of memory complaints to cognition and neuropathology. RESULTS: Baseline memory complaints (n = 1,310; 33% of 4,015) were associated with lower cognition and faster decline in all domains (global score estimate = -0.032, standard error = 0.004, p < 0.0001), during a mean follow-up of 6 (standard deviation = 2) years. Persons with memory complaints had higher dementia risk (hazard ratio = 1.64, 95% confidence interval [CI] = 1.42-1.89) and odds of pathologic Alzheimer disease (odds ratio [OR] = 1.96, 95% CI = 1.51-2.54), neocortical Lewy bodies (OR = 2.47, 95% CI = 1.54-3.96), and other neurodegenerative pathologies. Results for dementia risk were similar among blacks and whites. Among 2,937 older persons in a population-based cohort with similar data, the population-attributable risk for incident dementia due to memory complaints was 14.0% (95% CI = 2.6-23.0), and did not vary between the black and white groups. INTERPRETATION: Memory complaints are common in older black and white persons, and relate to cognitive decline, dementia risk, and neurodegenerative pathologies. Ann Neurol 2018;83:718-729.
Assuntos
Demência/etnologia , Demência/epidemiologia , Transtornos da Memória/etnologia , Transtornos da Memória/epidemiologia , Neuropatologia , Idoso , Idoso de 80 Anos ou mais , População Negra , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Humanos , Incidência , Vida Independente , Masculino , Transtornos da Memória/complicações , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , População BrancaRESUMO
INTRODUCTION: The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain. METHODS: A sample of 2794 participants with a clinical diagnosis for AD dementia were included. RESULTS: The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7-15.3), and annual incidence was 2.3% (1.7-2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14.6% (95% CI = 13.0, 16.2) in 1994-1997 to 14.7% (95% CI = 13.2, 16.2) in 2010-2012 (P = .84). The annual incidence of AD dementia was 2.8% (95% CI = 2.2, 3.2) in 1998-2000 and 2.2% (95% CI = 1.6, 2.8) in 2004-2006 (P = .20) and remained steady in 2010-2012. The prevalence and incidence among African Americans were approximately twice than those among European Americans. CONCLUSIONS: The prevalence and incidence of AD dementia showed substantial variation between 1994 and 2012, but no secular trend.
Assuntos
Doença de Alzheimer/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , População Branca/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Incidência , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: US-based studies have reported that older blacks perform worse than older whites on cognitive tests and have higher risk of Alzheimer disease dementia (AD). It is unclear whether these findings reflect differences in cognitive decline. METHODS: The Chicago Health and Aging Project followed individuals, 65+ years old (64% black, 36% white), for up to 18 years. Participants underwent triennial cognitive assessments; stratified randomized samples underwent assessments for AD. We compared black and white participants' cognitive performance, cognitive decline rate (N = 7,735), and AD incidence (N = 2,144), adjusting for age and sex. RESULTS: Black participants performed worse than white participants on the cognitive tests; 441 participants developed AD. Black participants' incident AD risk was twice that of whites (RR = 1.9; 95% CI, 1.4, 2.7), with 58 excess cases/1,000 occurring among blacks (95% CI, 28, 88). Among noncarriers of APOE ε4, blacks had 2.3 times the AD risk (95% CI, 1.5, 3.6), but among carriers, race was not associated with risk (RR = 1.1; 95% CI, 0.6, 2.0; Pinteraction = 0.05). However, cognitive decline was not faster among blacks: the black-white difference in 5-year change in global cognitive score was 0.007 standard unit (95% CI, -0.034, 0.047). Years of education accounted for a sizable portion of racial disparities in cognitive level and AD risk, in analyses using a counterfactual approach. CONCLUSIONS: The higher risk of AD among blacks may stem from lower level of cognitive test performance persisting throughout the observation period rather than faster rate of late-life cognitive decline. Disparities in educational attainment may contribute to these performance disparities. See video abstract at, http://links.lww.com/EDE/B299.
Assuntos
Doença de Alzheimer/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Envelhecimento Cognitivo , Disfunção Cognitiva/etnologia , População Branca/estatística & dados numéricos , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Chicago/epidemiologia , Cognição , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Fatores de Risco , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444(C), results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444(C), is associated with greater cell surface expression of CD33 in both subjects of European and African-American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) (r(2) > 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14(+)CD16(-) monocytes from 398 healthy subjects of three populations, we show that the rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 (pMETA = 2.36 × 10(-60)). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444(C) allele (P < 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility.
Assuntos
Doença de Alzheimer/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Negro ou Afro-Americano , Processamento Alternativo , Estudos de Casos e Controles , Éxons , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , População BrancaRESUMO
OBJECTIVE: Genome-wide association studies have linked variants in TREM2 (triggering receptor expressed on myeloid cells 2) and TREML2 with Alzheimer disease (AD) and AD endophenotypes. Here, we pursue a targeted analysis of the TREM locus in relation to cognitive decline and pathological features of AD. METHODS: Clinical, cognitive, and neuropathological phenotypes were collected in 3 prospective cohorts on aging (n = 3,421 subjects). Our primary analysis was an association with neuritic plaque pathology. To functionally characterize the associated variants, we used flow cytometry to measure TREM1 expression on monocytes. RESULTS: We provide evidence that an intronic variant, rs6910730(G) , in TREM1, is associated with an increased burden of neuritic plaques (p = 3.7 × 10(-4) ), diffuse plaques (p = 4.1 × 10(-3) ), and Aß density (p = 2.6 × 10(-3) ) as well as an increased rate of cognitive decline (p = 5.3 × 10(-3) ). A variant upstream of TREM2, rs7759295(C) , is independently associated with an increased tau tangle density (p = 4.9 × 10(-4) ), an increased burden of neurofibrillary tangles (p = 9.1 × 10(-3) ), and an increased rate of cognitive decline (p = 2.3 × 10(-3) ). Finally, a cytometric analysis shows that the TREM1 rs6910730(G) allele is associated with decreased TREM1 expression on the surface of myeloid cells (p = 1.7 × 10(-3) ). INTERPRETATION: We provide evidence that 2 common variants within the TREM locus are associated with pathological features of AD and aging-related cognitive decline. Our evidence suggests that these variants are likely to be independent of known AD variants and that they may work through an alteration of myeloid cell function.