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1.
Neurobiol Aging ; 80: 173-186, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201950

RESUMO

Variants associated with modulation of c-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease risk variants. We examined pleiotropic genetic effects on cognitive impairment conditioned on genetic variants (SNPs) associated with systemic inflammation as measured by CRP and with plasma lipids using data from the Health and Retirement Study. SNP enrichment was observed for cognitive impairment conditioned on the secondary phenotypes of plasma CRP and lipids. Fold enrichment of 100%-800% was observed for increasingly stringent p-value thresholds for SNPs associated with cognitive impairment conditional on plasma CRP, 80%-800% for low-density lipoprotein, and 80%-600% for total cholesterol. Significant associations (false discovery rate Q ≤ 0.05) between cognitive impairment, conditional with either CRP, low-density lipoprotein, or total cholesterol, were found for the locus on chromosome 19 that contains the APOE, TOMM40, APOC1, and PVRL2 genes. Relative numbers of significant SNPs in each of the genes differed by the conditional associations with the secondary phenotypes. Biological interpretation of both the genetic pleiotropy results and the individual genome-wide association results showed that the variants and proximal genes identified are involved in multiple pathological processes including cholesterol metabolism, inflammation, and mitochondrial transport. These findings are potentially important for Alzheimer's disease risk prediction and development of novel therapeutic approaches.

2.
Actas Urol Esp ; 2019 Jun 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31174878

RESUMO

OBJECTIVES: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. MATERIALS AND METHODS: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. RESULTS: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16-23.11; P=.03). CONCLUSIONS: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

3.
Aging Ment Health ; : 1-8, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31018653

RESUMO

BACKGROUND: A small but growing body of evidence supports a relationship between neighborhood socioeconomic status (NSES) and cognitive decline. Additional work is needed to characterize this relationship controlling for risk factors such as cardiovascular, cerebrovascular, and genetic risk factors. METHODS: Cognitive decline was assessed in association with NSES, and cardiovascular and cerebrovascular risk factors (heart disease, diabetes, hypertension, and stroke) in 8,198 individuals from the 1992-2010 waves of the Health and Retirement Study (HRS). Latent class trajectory analysis determined the number of cognitive trajectory classes that best fit the data, and a multinomial logistic regression model in the latent class framework assessed the risk for cognitive classes conferred by NSES index score and heart disease, diabetes, hypertension, and stroke across three trajectory classes of cognitive function. The analyses controlled for genetic risk for cognitive decline (including APOE genotype) and demographic variables, including education. RESULTS: The HRS sample was 57.6% female and 85.5% White, with a mean age of 67.5(3.5) years at baseline. The three-quadratic-class model best fit the data, where higher classes represented better cognitive function. Those with better cognitive function were mainly younger white females. Those in the highest quartile of NSES had 57% higher odds of being in the high cognitive function class. Heart disease, diabetes, hypertension, and stroke each increased the odds having of lower cognitive function. CONCLUSIONS: In examining the relationship of cognitive status with various variables, neighborhood socioeconomic status, cardiovascular risk, and cerebrovascular risk persisted across the cognitive trajectory classes.

4.
Int J Geriatr Psychiatry ; 34(10): 1403-1411, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31034676

RESUMO

OBJECTIVES: As people age and the incidence of dementia increases, studies of cognitive function continue to be of importance. Ascertaining cognitive data through different mechanisms is necessary to address missing data concerns. METHODS: The Dementia Questionnaire (DQ), which utilizes proxy-based assessments, is a potential tool to determine cognitive status in participants no longer being followed per traditional study protocol. The DQ is currently being used in the Supplemental Case Ascertainment Protocol (SCAP), which is being conducted in an ongoing study of postmenopausal women as part of the Women's Health Initiative Memory Study (WHIMS). RESULTS: Ninety-four percent of the 1260 SCAP participants were eligible because of being deceased. Those who are SCAP eligible were older, were less likely to be a minority, and were more likely to have hypertension, diabetes, and prior history of cardiovascular disease (CVD) as well as being a past or current smoker. SCAP added 109 cases of probable dementia to WHIMS. Risk factor relationships were modified upon inclusion of the SCAP cases including an attenuation of a hormone therapy effect and discovery of a hypertension effect. CONCLUSIONS: Augmenting clinic-based cases with proxy-based assessments is feasible and leads to increased incident cases of dementia. When planning future clinical trials, it may be of study benefit to include a protocol of proxy-based assessments, develop strong relationships with proxies early on in the study, and attempt to maintain this relationship throughout the lifespan of the trial.

5.
Int J Geriatr Psychiatry ; 34(5): 692-699, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30706571

RESUMO

OBJECTIVE: While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). METHODS: We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. RESULTS: One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ≤ 0.05). CONCLUSIONS: Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.

6.
Neuroimage ; 183: 401-411, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30130645

RESUMO

INTRODUCTION: The main goal of this work is to investigate the feasibility of estimating an anatomical index that can be used as an Alzheimer's disease (AD) risk factor in the Women's Health Initiative Magnetic Resonance Imaging Study (WHIMS-MRI) using MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized imaging database of AD patients and cognitively normal subjects. We called this index AD Pattern Similarity (AD-PS) scores. To demonstrate the construct validity of the scores, we investigated their associations with several AD risk factors. The ADNI and WHIMS imaging databases were collected with different goals, populations and data acquisition protocols: it is important to demonstrate that the approach to estimating AD-PS scores can bridge these differences. METHODS: MRI data from both studies were processed using high-dimensional warping methods. High-dimensional classifiers were then estimated using the ADNI MRI data. Next, the classifiers were applied to baseline and follow-up WHIMS-MRI GM data to generate the GM AD-PS scores. To study the validity of the scores we investigated associations between GM AD-PS scores at baseline (Scan 1) and their longitudinal changes (Scan 2 -Scan 1) with: 1) age, cognitive scores, white matter small vessel ischemic disease (WM SVID) volume at baseline and 2) age, cognitive scores, WM SVID volume longitudinal changes respectively. In addition, we investigated their associations with time until classification of independently adjudicated status in WHIMS-MRI. RESULTS: Higher GM AD-PS scores from WHIMS-MRI baseline data were associated with older age, lower cognitive scores, and higher WM SVID volume. Longitudinal changes in GM AD-PS scores (Scan 2 - Scan 1) were also associated with age and changes in WM SVID volumes and cognitive test scores. Increases in the GM AD-PS scores predicted decreases in cognitive scores and increases in WM SVID volume. GM AD-PS scores and their longitudinal changes also were associated with time until classification of cognitive impairment. Finally, receiver operating characteristic curves showed that baseline GM AD-PS scores of cognitively normal participants carried information about future cognitive status determined during follow-up. DISCUSSION: We applied a high-dimensional machine learning approach to estimate a novel AD risk factor for WHIMS-MRI study participants using ADNI data. The GM AD-PS scores showed strong associations with incident cognitive impairment and cross-sectional and longitudinal associations with age, cognitive function, cognitive status and WM SVID volume lending support to the ongoing validation of the GM AD-PS score.

7.
J Am Geriatr Soc ; 66(8): 1575-1580, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29972592

RESUMO

OBJECTIVES: To examine whether trajectories of global cognitive function over time in studies that change assessment protocols may be modeled based on an individual's performance relative to others in the study cohort. DESIGN: Extended follow-up of a cohort originally enrolled in a clinical trial of postmenopausal hormone therapy. SETTING: The Women's Health Initiative Memory Study switched from an in-person interview with the Modified Mini-Mental State Examination to a telephone-based interview with the modified Telephone Interview for Cognitive Status to assess global cognitive function over long-term follow-up. PARTICIPANTS: Women aged 75 to 92 (N=2,561). MEASUREMENTS: Annual cognitive assessments from participants, ranked according to age-, race- and ethnicity-adjusted performance levels, were used to identify distinct trajectories. Participants assigned to the resulting trajectories were compared for selected risk factor profiles. RESULTS: Our approach grouped participants into five trajectories according to relative cognitive performance over time. These groups differed significantly according to 3 known risk factors for cognitive decline-education level, apolipoprotein E-ϵ4 genotype, and type 2 diabetes mellitus-and a biomarker based on brain structure that has been linked to cognitive decline and Alzheimer's disease. Participants with consistently low relative levels of cognitive function over time and those whose relative performance over time declined to these levels tended to have poorer risk factor profiles. CONCLUSION: Longitudinal measures of an individual's relative performance on different assessment protocols for global cognitive function can be used to identify trajectories of change over time that appear to have internal validity with respect to known risk factors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-29718387

RESUMO

Objectives: Genetic risks for cognitive decline are not modifiable; however their relative importance compared to modifiable factors is unclear. We used machine learning to evaluate modifiable and genetic risk factors for Alzheimer's disease(AD), to predict cognitive decline. Methods: Health and Retirement Study participants, aged 65-90, with DNA and >2 cognitive evaluations, were included (n=7,142). Predictors included age, body mass index, gender, education, APOE ε4, CVD, hypertension, diabetes, stroke, neighborhood socio-economic status(NSES), and AD risk genes. Latent class trajectory analyses of cognitive scores determined the form and number of classes. Random Forests (RF) classification investigated predictors of cognitive trajectories. Performance metrics (accuracy, sensitivity and specificity) were reported. Results: Three classes were identified. Discriminating highest from lowest classes produced the best RF performance: accuracy=78%(1.0%), sensitivity=75%(1.0%) and specificity=81%(1.0%). Top ranked predictors were education, age, gender, stroke, NSES, and diabetes, APOE ε4 carrier status and BMI. When discriminating high from medium classes, top predictors were education, age, gender, stroke, diabetes, NSES and BMI. When discriminating medium from the low classes, education, NSES, age, diabetes and stroke were top predictors. Discussion: The combination of latent trajectories and RF classification techniques suggested that non-genetic factors contribute more to cognitive decline than genetic factors. Education was the most relevant predictor for discrimination.

9.
Alzheimers Dement ; 14(4): 454-461, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29396109

RESUMO

INTRODUCTION: We evaluated the association between neighborhood socioeconomic status (NSES) and sleep quality on cognitive decline in the Health and Retirement Study. METHODS: Health and Retirement Study participants (n = 8090), aged 65+ with DNA and multiple biennial cognitive observations (abbreviated Telephone Interview for Cognitive Status), were included. Participants were grouped into quartiles of NSES and sleep quality scores. We adjusted for apolipoprotein E ε4, demographic, and cardiovascular risk factors. Random effects modeling evaluated cognitive change over time. RESULTS: NSES and sleep were significantly associated with cognitive decline, and there was a significant interaction between them (P = .02). Significant differences between high/low NSES and high/low sleep quality (P < .0001) were found. DISCUSSION: Sleep and NSES were associated with cognitive decline; the association between sleep and cognition appeared stronger among those with low NSES. The association between low NSES, poor sleep quality, and cognitive decline was roughly equivalent to the association between apolipoprotein E ε4 and cognitive decline.

10.
PLoS Med ; 15(1): e1002482, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29370177

RESUMO

BACKGROUND: The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. METHODS AND FINDINGS: Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer's Disease [EASE-AD]). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703-11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516-7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373-9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047-4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-ß (Aß) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples. CONCLUSIONS: We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD.

11.
Exp Aging Res ; 44(1): 1-17, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29303475

RESUMO

Background/Study Context: Conceptual frameworks are analytic models at a high level of abstraction. Their operationalization can inform randomized trial design and sample size considerations. METHODS: The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) conceptual framework was empirically tested using structural equation modeling (N=2,802). ACTIVE was guided by a conceptual framework for cognitive training in which proximal cognitive abilities (memory, inductive reasoning, speed of processing) mediate treatment-related improvement in primary outcomes (everyday problem-solving, difficulty with activities of daily living, everyday speed, driving difficulty), which in turn lead to improved secondary outcomes (health-related quality of life, health service utilization, mobility). Measurement models for each proximal, primary, and secondary outcome were developed and tested using baseline data. Each construct was then combined in one model to evaluate fit (RMSEA, CFI, normalized residuals of each indicator). To expand the conceptual model and potentially inform future trials, evidence of modification of structural model parameters was evaluated by age, years of education, sex, race, and self-rated health status. RESULTS: Preconceived measurement models for memory, reasoning, speed of processing, everyday problem-solving, instrumental activities of daily living (IADL) difficulty, everyday speed, driving difficulty, and health-related quality of life each fit well to the data (all RMSEA < .05; all CFI > .95). Fit of the full model was excellent (RMSEA = .038; CFI = .924). In contrast with previous findings from ACTIVE regarding who benefits from training, interaction testing revealed associations between proximal abilities and primary outcomes are stronger on average by nonwhite race, worse health, older age, and less education (p < .005). CONCLUSIONS: Empirical data confirm the hypothesized ACTIVE conceptual model. Findings suggest that the types of people who show intervention effects on cognitive performance potentially may be different from those with the greatest chance of transfer to real-world activities.


Assuntos
Envelhecimento/psicologia , Transtornos Cognitivos/terapia , Avaliação Geriátrica/métodos , Educação em Saúde/métodos , Transtornos da Memória/terapia , Modelos Psicológicos , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/psicologia , Feminino , Nível de Saúde , Humanos , Masculino , Transtornos da Memória/psicologia , Resolução de Problemas , Qualidade de Vida , Projetos de Pesquisa
12.
Alzheimers Dement ; 14(3): 318-329, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29055815

RESUMO

INTRODUCTION: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. METHODS: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. RESULTS: Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. DISCUSSION: Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms.

13.
J Am Geriatr Soc ; 66(1): 120-126, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29082505

RESUMO

OBJECTIVES: To determine whether long-term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF) in individuals with type 2 diabetes mellitus. DESIGN: Postrandomization assessment of CBF. SETTING: Action for Health in Diabetes multicenter randomized controlled clinical trial. PARTICIPANTS: Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310). INTERVENTIONS: A multidomain intensive lifestyle intervention (ILI) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE), a control condition. MEASUREMENTS: Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization. RESULTS: Weight changes from baseline to time of MRI averaged -6.2% for ILI and -2.8% for DSE (P < .001), and increases in self-reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL/100 g per minute, 95% confidence interval (CI) = 0.07-6.70 mL/100 g per minute) and occipital lobes (3.52 mL/100 g per minute, 95% CI = 0.20-6.84 mL/100 g per minute). In ILI, greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02). CONCLUSIONS: Long-term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF.

14.
JACC Heart Fail ; 5(9): 642-651, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28822744

RESUMO

OBJECTIVES: This study examined the association of aldosterone and plasma renin activity (PRA) with incident cardiovascular disease (CVD), using a composite endpoint of coronary heart disease, stroke, and/or heart failure and mortality among African Americans in the Jackson Heart Study. BACKGROUND: There is a paucity of data for the association of aldosterone and PRA with incident CVD or all-cause mortality among community-dwelling African Americans. METHODS: A total of 4,985 African American adults, 21 to 94 years of age, were followed for 12 years. Aldosterone, PRA, and cardiovascular risk factors were collected at baseline (from 2000 to 2004). Incident events included coronary heart disease and stroke (assessed from 2000 to 2011) and heart failure (assessed from 2005 to 2011). Cox models were used to estimate hazard ratios (HRs) for incident CVD and mortality, adjusting for age, sex, education, occupation, current smoking, physical activity, dietary intake, and body mass index. RESULTS: Among 4,160 participants without prevalent CVD over a median follow-up of 7 years, there were 322 incident CVD cases. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HR of 1.26 (95% confidence intervals [CI]: 1.14 to 1.40) and 1.16 (95% CI: 1.02 to 1.33) for incident CVD, respectively. Over a median of 8 years, 513 deaths occurred among 4,985 participants. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HRs of 1.13 (95% CI: 1.04 to 1.23) and 1.12 (95% CI: 1.01 to 1.24) for mortality, respectively. CONCLUSIONS: Elevated aldosterone and PRA may play a significant role in the development of CVD and all-cause mortality among African Americans.


Assuntos
Aldosterona/fisiologia , Doenças Cardiovasculares/mortalidade , Renina/fisiologia , Adulto , Afro-Americanos/etnologia , Idoso , Idoso de 80 Anos ou mais , Aldosterona/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/etnologia , Causas de Morte , Doença das Coronárias/etnologia , Doença das Coronárias/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/mortalidade , Estudos Prospectivos , Renina/metabolismo , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologia , Adulto Jovem
15.
Contemp Clin Trials Commun ; 6: 1-8, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28649668

RESUMO

BACKGROUND: For over 20 years, normative data has guided the prescription of physical activity. This data has since been applied to research and used to plan interventions. While this data seemingly provides accurate estimates of the metabolic cost of daily activities in young adults, the accuracy of use among older adults is less clear. As such, a thorough evaluation of the metabolic cost of daily activities in community dwelling adults across the lifespan is needed. METHODS: The Metabolic Costs of Daily Activity in Older Adults Study is a cross-sectional study designed to compare the metabolic cost of daily activities in 250 community dwelling adults across the lifespan. Participants (20+ years) performed 38 common daily activities while expiratory gases were measured using a portable indirect calorimeter (Cosmed K4b2). The metabolic cost was examined as a metabolic equivalent value (O2 uptake relative to 3.5 milliliter• min-1•kg-1), a function of work rate - metabolic economy, and a relative value of resting and peak oxygen uptake. RESULTS: The primary objective is to determine age-related differences in the metabolic cost of common lifestyle and exercise activities. Secondary objectives include (a) investigating the effect of functional impairment on the metabolic cost of daily activities, (b) evaluating the validity of perception-based measurement of exertion across the lifespan, and (c) validating activity sensors for estimating the type and intensity of physical activity. CONCLUSION: Results of this study are expected to improve the effectiveness by which physical activity and nutrition is recommended for adults across the lifespan.

16.
Alzheimers Dement ; 13(11): 1187-1196, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28531379

RESUMO

INTRODUCTION: The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk. METHODS: Baseline food frequency questionnaires from n = 7085 women (aged 65-79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups. RESULTS: Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86-1.20); group 3-HR: 0.99 (0.82-1.18); and group 4-HR: 1.27 (1.06-1.52). CONCLUSIONS: Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.


Assuntos
Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Demência/epidemiologia , Demência/etiologia , Dieta/efeitos adversos , Inflamação/epidemiologia , Saúde da Mulher , Idoso , Disfunção Cognitiva/diagnóstico , Inquéritos sobre Dietas , Feminino , Humanos , Incidência , Inflamação/etiologia , Modelos de Riscos Proporcionais , Inquéritos e Questionários
17.
Alzheimers Dement ; 13(9): 965-984, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28341160

RESUMO

INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. METHODS: Fasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted. RESULTS: Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aß1-42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease. DISCUSSION: Metabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Doenças Metabólicas/etiologia , Redes e Vias Metabólicas/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Aminoácidos/sangue , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/metabolismo , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Estudos de Coortes , Estudos Transversais , Jejum , Feminino , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/líquido cefalorraquidiano , Doenças Metabólicas/diagnóstico por imagem , Metabolômica/métodos , Fragmentos de Peptídeos/metabolismo , Fosfatidilcolinas/sangue , Fosfatidilcolinas/metabolismo , Esfingomielinas/sangue , Tiazóis/metabolismo , Proteínas tau/líquido cefalorraquidiano
18.
J Am Heart Assoc ; 6(2)2017 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-28154164

RESUMO

BACKGROUND: Studies exploring the association between insulin resistance (IR) and cardiovascular disease in blacks have not been conclusive, especially for coronary heart disease (CHD). The McAuley index and homeostasis model assessment of IR (HOMA-IR) perform differently in predicting cardiovascular disease. We investigated this association in the Jackson Heart Study, a large longitudinal cohort of blacks. METHODS AND RESULTS: IR was estimated for 3565 participants without diabetes mellitus and cardiovascular disease at baseline using the McAuley index and HOMA-IR, and their associations with incident CHD and stroke (composite outcome) were compared. A lower McAuley index and higher HOMA-IR are indicative of IR. Cox regression analysis was used to estimate adjusted hazard ratios for incident CHD and/or stroke. There were 158 events (89 CHD-only, 58 stroke-only, and 11 CHD/stroke) over a median follow-up of 8.4 years. After adjustment for demographic factors, the risk of the composite outcome decreased with each SD increase in the McAuley index (hazard ratio 0.80; 95% CI: 0.67-0.96), with no attenuation after further accounting for CHD and stroke risk factors. When considered individually, McAuley index and HOMA-IR were associated with CHD (hazard ratio 0.71, 95% CI: 0.55-0.92 and hazard ratio 1.33, 95% CI: 1.03-1.72, respectively), but not stroke risk. The logHOMA-IR and CHD association was present in men, but not in women (Pinteraction=0.01). CONCLUSIONS: Both HOMA-IR and the McAuley index demonstrate strong associations with CHD but not stroke risk in blacks. The logHOMA-IR and CHD association was present in men, but not in women.


Assuntos
Afro-Americanos/etnologia , Doença das Coronárias/etnologia , Resistência à Insulina , Medição de Risco/métodos , Acidente Vascular Cerebral/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/sangue , Diabetes Mellitus , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Acidente Vascular Cerebral/sangue , Estados Unidos/epidemiologia , Adulto Jovem
20.
Front Hum Neurosci ; 10: 495, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27790103

RESUMO

Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters < 2.5 µm) has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 women (aged 71-89) in the Women's Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space). Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average) exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM) and white matter (WM) maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked smaller WM volumes to PM2.5, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

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