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1.
J Stroke Cerebrovasc Dis ; 30(6): 105764, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33823461

RESUMO

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP) <120 mm Hg vs. <140 mm Hg. In a subset of participants, the SPRINT MIND ancillary study performed a baseline MRI and measured white matter hyperintensity volume (WMHv). In this secondary analysis, we evaluated the association between baseline WMHv and cardiovascular events during follow-up in the overall sample. METHODS: The primary outcome was the same as SPRINT, a composite of stroke, myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, or cardiovascular death. We fit Cox models to the primary outcome and report adjusted hazard ratios (HR) for log-transformed WMHv and quartiles of WMHv. RESULTS: Among 717 participants, the median (IQR) baseline WMHv was 1.62 (0.66-3.98) mL. The primary outcome occurred in 51/719 (7.1%). The median WMHv was higher in patients with the primary outcome (3.40 mL versus 1.56 mL, p < 0.001). In adjusted models, WMHv as a log-transformed continuous variable was associated with the primary outcome (HR 1.44, 95% CI 1.15-1.80). The highest quartile of WMHv, compared to the lowest, was also independently associated with the primary outcome (HR 3.21, 95% CI 1.27-8.13). CONCLUSIONS: We found that the baseline volume of WMH was associated with future CVD risk in SPRINT MIND. Prospective clinical trials with larger sample sizes than the current study are needed to determine whether intensive BP lowering can reduce the high cardiovascular risk in patients with WMH.

2.
Semin Neurol ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33851395

RESUMO

The pace of understanding cognitive decline and dementia has rapidly accelerated over the past decade, with constantly evolving insights into the vascular contributions to cognitive impairment and dementia (VCID). Notably, more overlap has been discovered in the pathophysiology between what was previously understood to be Alzheimer's disease and VCID, leading to a heightened emphasis on disease prevention through early and aggressive control of vascular risk factors. One particularly vulnerable population may be those with cardiac disease, as they are at risk for cerebrovascular disease, which itself can lead to dementia, and increasing evidence supports cognitive impairment in disease processes such as heart failure and atrial fibrillation, independent of ischemic stroke, suggesting other potential mechanisms. In this article, we review the evidence supporting the relationship between cardiac disease, cerebrovascular disease, and cognitive decline and discuss the ongoing and future research efforts aimed at defining the important relationship between these entities.

3.
Neurology ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790039

RESUMO

OBJECTIVE: To develop a risk prediction score identifying intracerebral hemorrhage (ICH) patients at low risk for critical care. METHODS: We retrospectively analyzed data of 451 ICH patients between 2010-2018. The sample was randomly divided in a development and a validation cohort. Logistic regression was used to develop a risk score by weighting independent predictors of ICU needs based on strength of association. The risk score was tested in the validation cohort, and externally validated in a dataset from another institution. RESULTS: The rate of ICU interventions was 80.3%. Systolic blood pressure (SBP), Glasgow Coma Scale (GCS), intraventricular hemorrhage (IVH), and ICH volume were independent predictors of critical care, resulting in the following point assignments for the INtensive care TRiaging IN Spontaneous IntraCerebral hemorrhage (INTRINSIC) score: SBP 160-190 mm Hg (1 point), SBP >190 mm Hg (3 points); GCS 8-13 (1 point), GCS <8 (3 points); ICH volume 16-40 cm3 (1 point), ICH volume >40 cm3 (2 points); and presence of IVH (1 point), with values ranging between 0-9. Among patients with a score of 0 and no ICU needs during their emergency department stay, 93.6% remained without critical care needs. In an external validation cohort of ICH patients, the INTRINSIC score achieved an AUC of 0.823 (95% CI 0.782-0.863). A score <2 predicted absence of critical care needs with 48.5% sensitivity and 88.5% specificity, and a score <3 predicted absence of critical care needs with 61.7% sensitivity and 83.0% specificity. CONCLUSION: The INTRINSIC score identifies ICH patients at low risk for critical care interventions. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the INTRINSIC score identifies ICH patients at low risk for critical care interventions.

4.
J Neurol Sci ; 424: 117404, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33761379

RESUMO

BACKGROUND: Limited data exists about stroke risk factors and outcomes in sub-Saharan African countries, including Zambia. We aim to fill this gap by describing features of hospitalized stroke patients at University Teaching Hospital (UTH), the national referral hospital in Lusaka, Zambia. METHODS: We conducted a retrospective study of consecutive adults with stroke admitted to UTH's inpatient neurology service from October 2018 to March 2019. Strokes were classified as ischemic or hemorrhagic based on CT scan results and unknown if CT scan was not obtained. Chi-square analyses and t-tests were used to compare characteristics between cohorts with differing stroke subtypes. RESULTS: Adults with stroke constituted 43% (n = 324) of all neurological admissions, had an average age of 60 ± 18 years, and 62% of the cohort was female. Stroke subtypes were 58% ischemic, 28% hemorrhagic, and 14% unknown. Hypertension was present in 80% of all strokes and was significantly associated with hemorrhagic stroke (p = 0.03). HIV was present in 18% of all strokes and did not significantly differ by stroke subtype. Diabetes (16%), heart disease (34%), atrial fibrillation (9%), and past medical history of stroke (22%) were all significantly more common in patients with ischemic stroke (p < 0.05). In-hospital mortality was 24% overall and highest among individuals with hemorrhagic strokes (33%, p = 0.005). CONCLUSIONS: This Zambian stroke cohort is notable for its young age, significant HIV burden, high in-hospital mortality, and high rates of uncontrolled hypertension. Our results demonstrate Zambia's substantial stroke burden, significant contribution of HIV to stroke, and the need to improve primary stroke prevention.

5.
Alzheimers Dement ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687142

RESUMO

INTRODUCTION: Head injury is associated with significant morbidity and mortality. Long-term associations of head injury with dementia in community-based populations are less clear. METHODS: Prospective cohort study of 14,376 participants (mean age 54 years at baseline, 56% female, 27% Black, 24% with head injury) enrolled in the Atherosclerosis Risk in Communities (ARIC) Study. Head injury was defined using self-report and International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. Dementia was defined using cognitive assessments, informant interviews, and ICD-9/10 and death certificate codes. RESULTS: Head injury was associated with risk of dementia (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.3-1.57), with evidence of dose-response (1 head injury: HR = 1.25, 95% CI = 1.13-1.39, 2+ head injuries: HR = 2.14, 95% CI = 1.86-2.46). There was evidence for stronger associations among female participants (HR = 1.69, 95% CI = 1.51-1.90) versus male participants (HR = 1.15, 95% CI = 1.00-1.32), P-for-interaction < .001, and among White participants (HR = 1.55, 95% CI = 1.40-1.72) versus Black participants (HR = 1.22, 95% CI = 1.02-1.45), P-for-interaction = .008. DISCUSSION: In this community-based cohort with 25-year follow-up, head injury was associated with increased dementia risk in a dose-dependent manner, with stronger associations among female participants and White participants.

6.
JAMA Netw Open ; 4(2): e210169, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630089

RESUMO

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women. Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. Design, Setting, and Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. Exposure: Sex. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61). Conclusions and Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.


Assuntos
Disfunção Cognitiva/epidemiologia , Reserva Cognitiva , Função Executiva , Memória , Idoso , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Risco , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologia
9.
J Am Heart Assoc ; 10(5): e014270, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33586464

RESUMO

Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow-up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time-varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow-up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio [HR], 0.53; 95% CI, 0.30-0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05-0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models. Conclusions In this US community-based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.

10.
Alzheimers Dement ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527720

RESUMO

INTRODUCTION: Clinic-based study samples, including the Alzheimer's Disease Neuroimaging Initiative (ADNI), offer rich data, but findings may not generalize to community-based settings. We compared associations in ADNI to those in the Atherosclerosis Risk in Communities (ARIC) study to assess generalizability across the two settings. METHODS: We estimated cohort-specific associations among risk factors, cognitive test scores, and neuroimaging outcomes to identify and quantify the extent of significant and substantively meaningful differences in associations between cohorts. We explored whether using more homogenous samples improved comparability in effect estimates. RESULTS: The proportion of associations that differed significantly between cohorts ranged from 27% to 34% across sample subsets. Many differences were substantively meaningful (e.g., odds ratios [OR] for apolipoprotein E ε4 on amyloid positivity in ARIC: OR = 2.8, in ADNI: OR = 8.6). DISCUSSION: A higher proportion of associations differed significantly and substantively than would be expected by chance. Findings in clinical samples should be confirmed in more representative samples.

11.
Brain Imaging Behav ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439369

RESUMO

Imaging markers of cerebrovascular disease and Alzheimer's disease (AD) are implicated in mobility impairment in older adults, but few studies have examined these relationships longitudinally in a racially-diverse population-based sample. At Visit 5 (2011-13) of the ARIC Study, 1859 participants had usual pace gait speed (cm/s) assessed and brain MRI (mean age = 76.3, 28.5% Black) and PET (n = 343; mean age = 75.9, 42.6% Black) measures including total/regional brain volume (cm3), white matter hyperintensities (WMH; cm3), infarcts (present/absent), microbleeds (count) and global beta-amyloid (Aß). Participants returned at Visit 6 (n = 1264, 2016-17) and Visit 7 (n = 1108, 2018-19) for follow-up gait speed assessments. We used linear regression to estimate effects of baseline infarct presence, higher microbleed count, and a one interquartile range (IQR) poorer measures of continuous predictors (-1 IQR total brain volume, temporal-parietal lobe meta region of interest(ROI); +1 IQR WMH volume, global Aß SUVR) on cross-sectional gait speed and change in gait speed adjusting for age, sex, education, study site, APOE e4, estimated intracranial volume, BMI, and cardiovascular risk factors. Cross-sectionally, slower gait speed outcome was associated with higher WMH volume, -3.38 cm/s (95%CI:-4.71, -2.04), infarct presence, -5.60 cm/s (-7.69, -3.51), microbleed count, -2.20 cm/s (-3.20, -0.91), smaller total brain volume, -9.26 cm/s (-12.1, -6.43), and smaller temporal-parietal lobe ROI -6.28 cm/s (-8.28, -4.28). Longitudinally, faster gait speed outcome decline was associated with higher WMH volume, -0.27 cm/s/year, (-0.51, -0.03) and higher global Aß SUVR, -0.62 cm/s/year (-1.20, -0.03). Both cerebrovascular and AD pathology may contribute to mobility decline commonly seen with aging.

12.
J Gen Intern Med ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469773

RESUMO

BACKGROUND: Whether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD. OBJECTIVE: To determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults. DESIGN: We leveraged data from the Atherosclerosis Risk in Communities Study. PARTICIPANTS: Thirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study. MAIN MEASURES: Each SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD. KEY RESULTS: Among persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison). CONCLUSIONS: Midlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality.

13.
Stroke ; 52(3): 878-886, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33467879

RESUMO

BACKGROUND AND PURPOSE: Life's Simple 7 (LS7) is a metric for cardiovascular health based on the 7 domains of smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. Because they may be targeted for secondary prevention purposes, we hypothesized that stroke survivors would experience improvement in LS7 score over time compared with people who did not experience a stroke. We addressed this hypothesis in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) cohort of Black and White adults enrolled between 2003 and 2007. METHODS: Participants who had LS7 data at baseline, were stroke-free at baseline, had a 10-year follow-up visit, and either did not have a stroke or had an ischemic stroke >1 year before follow-up were included (N=7569). Among these participants, 149 (2.0%) had an adjudicated ischemic stroke between the LS7 assessments. LS7 scores were classified as 0 to 2 points for each domain for a maximum score of 14, with higher scores representing better health. Multivariable linear regression was used to test the association of ischemic stroke with change in LS7 score. Covariates included baseline LS7 score, age, race, sex, education, and geographic region. RESULTS: The 149 stroke survivors had an average of 4.9 years (SD=2.5) of follow-up from the stroke event to the second LS7 assessment. After adjusting for covariates, participants who experienced an ischemic stroke showed 0.28 points more decline in total LS7 score (P=0.03) than those who did not experience a stroke. CONCLUSIONS: Stroke survivors did not experience improvements in cardiovascular health due to secondary prevention after ischemic stroke. On the contrary, they experienced significantly greater decline, indicating the need for greater efforts in secondary prevention after a stroke.

14.
J Am Heart Assoc ; 10(2): e018766, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33442991

RESUMO

Background Left atrial (LA) function is important in stroke, but often poorly characterized. We evaluated the association of 2-dimensional speckle tracking echocardiography LA variables with stroke subtype (cardioembolic stroke [CS] or cryptogenic stroke versus other). The hypothesis is worse LA active function is associated with CS, but not cryptogenic strokes. Methods and Results In this prospective cohort (2017-2019), left ventricular/LA structure and function were quantified by 2-dimensional and speckle tracking echocardiography in 151 patients with stroke. Strain/strain rate curves for the 3 components of the LA cycle, ie, (1) Reservoir (global longitudinal strain [Srmax]), (2) Conductive (early LA Sr [Sre]), and (3) Active (late LA strain [Sra]) were evaluated, masked to stroke subtype. Associations of cardiac features with stroke subtype were tested using multivariable logistic regressions. Odds of CS were increased in patients with a larger LA systolic diameter (odds ratio [OR], 2.96, 95% CI, 1.14-7.69) but reduced in patients with a higher Srmax (better reservoir) (OR, 0.80, 95% CI, 0.67-0.97). Lower Sra (worse function) was associated with an increased odds of CS (OR, 1.72, 95% CI, 1.07-2.76) but not independent of atrial fibrillation. Higher active LA emptying fraction (better active phase) was associated with reduced odds of CS (OR, 0.74, 95% CI, 0.57-0.95) or cryptogenic stroke (OR, 0.82, 95% CI, 0.68-0.98) versus other subtypes; other associations between cryptogenic stroke and speckle tracking echocardiography were not found. Conclusions Markers of LA structure and function were associated with CS. Similar associations were not found for cryptogenic stroke, which might suggest different underlying mechanisms, given study limitations. Further understanding could aid stroke diagnosis and secondary stroke prevention research.

15.
Neurology ; 96(7): e964-e974, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33408144

RESUMO

OBJECTIVE: To test the hypothesis that greater levels of leisure-time moderate to vigorous intensity physical activity (MVPA) in midlife or late life are associated with larger gray matter volumes, less white matter disease, and fewer cerebrovascular lesions measured in late life, we utilized data from 1,604 participants enrolled in the Atherosclerosis Risk in Communities study. METHODS: Leisure-time MVPA was quantified using a past-year recall, interviewer-administered questionnaire at baseline and 25 years later and classified as none, low, middle, and high at each time point. The presence of cerebrovascular lesions, white matter hyperintensities (WMH), white matter integrity (mean fractional anisotropy [FA] and mean diffusivity [MD]), and gray matter volumes were quantified with 3T MRI in late life. The odds of cerebrovascular lesions were estimated with logistic regression. Linear regression estimated the mean differences in WMH, mean FA and MD, and gray matter volumes. RESULTS: Among 1,604 participants (mean age 53 years, 61% female, 27% Black), 550 (34%), 176 (11%), 250 (16%), and 628 (39%) reported no, low, middle, and high MVPA in midlife, respectively. Compared to no MVPA in midlife, high MVPA was associated with more intact white matter integrity in late life (mean FA difference 0.13 per SD [95% confidence interval (CI) 0.004, 0.26]; mean MD difference -0.11 per SD [95% CI -0.21, -0.004]). High MVPA in midlife was also associated with a lower odds of lacunar infarcts (odds ratio 0.68, 95% CI 0.46, 0.99). High MVPA was not associated with gray matter volumes. High MVPA compared to no MVPA in late life was associated with most brain measures. CONCLUSION: Greater levels of physical activity in midlife may protect against cerebrovascular sequelae in late life.


Assuntos
Encéfalo/diagnóstico por imagem , Exercício Físico/fisiologia , Substância Cinzenta/diagnóstico por imagem , Atividades de Lazer , Substância Branca/diagnóstico por imagem , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tamanho do Órgão/fisiologia
16.
Am Heart J ; 235: 36-43, 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33503409

RESUMO

BACKGROUND: We recently described the association between periodontal disease (PD) and stroke risk. PURPOSE: The purpose of this study was to test the association between PD, dental care utilization and incident atrial fibrillation (AF), as well as AF as a mediator to PD- stroke association. METHODS: In dental cohort of the Atherosclerosis Risk in Communities Study (ARIC), participants without prior AF underwent full-mouth periodontal measurements. PD was defined on an ordinal scale as healthy (referent), mild, moderate and severe. In ARIC main cohort, participants were classified as regular or episodic dental care users. These patients were followed for AF, over 17 years. Cox proportional hazards models adjusted for AF risk factors were used to study relationships between PD severity, dental care utilization and AF. Mediation analysis was used to test if AF mediated the PD- stroke association. RESULTS: In dental ARIC cohort, 5,958 were assessed without prior AF, 754 were found to have AF. Severe PD was associated with AF on both univariable (crude HR, 1.54; 95% CI, 1.26-1.87) and multivariable (adjusted HR, 1.31, 95% CI, 1.06-1.62) analyses. Mediation analysis suggested AF mediates the association between PD and stroke. In the main ARIC cohort, 9,666 participants without prior AF were assessed for dental care use, 1558 were found to have AF. Compared with episodic users, regular users had a lower risk for AF on univariable (crude HR, 0.82, 95% CI, 0.74-0.90) and multivariable (adjusted HR, 0.88, 95% CI, 0.78-0.99) analyses. CONCLUSIONS: PD is associated with AF. The association may explain the PD-stroke risk. Regular users had a lower risk of incident AF compared with episodic users.

17.
J Am Heart Assoc ; : e018399, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289449

RESUMO

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of ß-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m2; (2) P-wave terminal force >5000 µV×ms; and (3) serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) >250 pg/mL. Cross-sectional associations between global cortical ß-amyloid (>1.2 standardized uptake value ratio) and adjudicated history of AF and atrial cardiopathy, each, were evaluated using multivariable logistic regression. Participants (mean age, 76 years) were 56% women and 42% Black individuals. Odds of elevated florbetapir standardized uptake value ratio were significantly increased among those with atrial cardiopathy (odds ratio, 1.81; 95% CI, 1.02-3.22) and doubled for those with enlarged left atrial volume index after adjustment for demographics/risk factors (95% CI, 1.04-4.61). There was no association between P-wave terminal force or NT-proBNP and elevated florbetapir standardized uptake value ratio, nor between AF and elevated standardized uptake value ratio. Conclusions Among healthy, nondemented community-dwelling older individuals, we report an association between atrial cardiopathy, left atrial volume index, and elevated brain amyloid, by positron emission tomography, without a similar association in individuals with AF. Potential limitations include reverse causation and survival bias. Ongoing work will help determine if changes in cardiac structure and function precede or occur simultaneously with amyloid deposition.

18.
Nat Commun ; 11(1): 6285, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293549

RESUMO

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

19.
J Am Heart Assoc ; 9(22): e017546, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33170065

RESUMO

Background The impact of the new 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline on dementia risk at the population level has not been evaluated. Methods and Results We studied dementia-free participants in the ARIC (Atherosclerosis Risk in Communities) Study cohort in 1987 to 1989. Hypertension was defined by 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and 2017 ACC/AHA guidelines using blood pressure measured at baseline. Dementia was defined using adjudicated consensus diagnoses, informant telephone interviews, and discharge codes from hospitalizations and death certificates. Cox regression estimated hazard ratios (HRs) for dementia and 95% CIs by hypertension categories, adjusting for confounders. Population attributable fraction of dementia was calculated by hypertension categories. Among 13 971 participants followed up for a median of 23 years, 1381 dementia cases were identified. Prevalence of hypertension was 34% and 48%, according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and ACC/AHA criteria, respectively. HRs (95% CIs) compared with normal blood pressure, according to ACC/AHA categories, were 1.35 (1.12-1.61) for elevated blood pressure, 1.28 (1.07-1.52) for hypertension stage 1, and 1.36 (1.18-1.57) for hypertension stage 2. Population attributable fractions (95% CIs) of dementia from blood pressure categories were 3% (1%-5%), 3% (1%-5%), and 9% (4%-14%), respectively. Population attributable fractions (95% CIs) using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure categories were 6% (3%-9%) for prehypertension, 0% (-2% to 2%) for hypertension stage 1, and 9% (5%-13%) for hypertension stage 2. Conclusions Risk of dementia increased across hypertension categories defined by ACC/AHA guidelines. The population impact on dementia incidence using ACC/AHA categories was similar to the impact of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

20.
Neurobiol Aging ; 97: 65-72, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160263

RESUMO

We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Communities-Positron Emission Tomography study participants (n = 88; mean age: 77 years [standard deviation: 6]). Neuronal extracellular vesicle levels of phosphorylated insulin signaling cascade proteins were quantified. Brain volume and white matter hyperintensity (WMH) volume were assessed using 3T magnetic resonance imaging. After adjusting for demographic variables and extracellular vesicle marker Alix, higher levels of a neuronal insulin signaling composite measure were associated with lower WMH and greater temporal lobe volume. Secondary analyses found the levels of downstream protein kinases involved in cell survival (p70S6K) and tau phosphorylation/neuroinflammation (GSK-3ß) to be most strongly associated with WMH and temporal lobe volume, respectively. Associations between neuronal insulin signaling and lower WMH volume were attenuated in participants with elevated cortical amyloid. These results suggest that enhanced neuronal proximal insulin signaling is associated with preserved brain structure in nondemented older adults.

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