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OBJECTIVE: Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment. METHODS: In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment. Brain magnetic resonance images collected at baseline and follow-up were read for SBI. The occurrence of mild cognitive impairment (MCI) or probable dementia (PD) was evaluated. RESULTS: For 667 participants at baseline, SBI were identified in 75 (11%). At median 3.9 years follow-up, 12 of 457 had new SBI on magnetic resonance imaging (5 intensive, 7 standard), whereas 8 had clinical stroke (4 per group). Baseline SBI (subhazard ratio [sHR] = 3.90; 95% CI 1.49 to 10.24; p = 0.006), but not treatment group, was associated with new SBI or stroke. For participants with baseline SBI, intensive treatment reduced their risk for recurrent SBI or stroke (sHR = 0.050; 95% CI 0.0031 to 0.79; p = 0.033). Baseline SBI also increased risk for MCI or PD during follow-up (sHR = 2.38; 95% CI 1.23 to 4.61; p = 0.010). INTERPRETATION: New cerebral ischemic events were infrequent, but intensive treatment mitigated the increased risk for participants with baseline SBI, indicating primary prevention SBP goals are still appropriate when SBI are present. ANN NEUROL 2024;95:866-875.
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Anti-Hipertensivos , Infarto Encefálico , Disfunção Cognitiva , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hipertensão/complicações , Pressão Sanguínea/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , DemênciaRESUMO
Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement.
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Apêndice Atrial , Fibrilação Atrial , Embolia , AVC Isquêmico , Acidente Vascular Cerebral , Pessoa de Meia-Idade , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Anticoagulantes/uso terapêutico , Embolia/complicações , AVC Isquêmico/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. METHODS: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. RESULTS: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03-2.23], BA aHR, 1.28 [95% CI, 1.02-1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02-3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07-8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. CONCLUSIONS: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.
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Noma , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos de Coortes , Encéfalo , Artéria Cerebral Média , Fatores de RiscoRESUMO
INTRODUCTION: Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. METHODS: We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI-cognitive study (mean age 64 ± 8 years, 61% women, 67% Hispanic, 18% non-Hispanic Black, 15% non-Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0 ± 0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. RESULTS: In adjusted models, ePWV (mean 11 ± 2 m/s) was significantly associated with cognition (b = -0.100, 95% CI, -0.120, -0.080) and cognitive change over time (b = -0.063, 95% CI, -0.082, -0.045). Effect modification by race and sex was found. DISCUSSION: In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age-related cognitive decline. HIGHLIGHTS: ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals. After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory. After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term. The association between ePWV and episodic memory decline was stronger in females.
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Cognição , Análise de Onda de Pulso , Rigidez Vascular , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Cognição/fisiologia , Rigidez Vascular/fisiologia , Cidade de Nova Iorque , Imageamento por Ressonância Magnética , Testes Neuropsicológicos/estatística & dados numéricos , Disfunção Cognitiva/etnologia , Disfunção Cognitiva/fisiopatologia , EtnicidadeRESUMO
BACKGROUND: Although protective in secondary stroke prevention of intracranial arterial stenosis (ICAS), it is uncertain if the benefits of leisure time physical activity (LTPA) extend to asymptomatic ICAS or extracranial carotid stenosis (ECAS). Therefore, we sought to determine LTPA's relationship with ECAS and ICAS in a stroke-free, race-ethnically diverse cohort. METHODS: This cross-sectional study included participants from the magnetic resonance imaging substudy of the Northern Manhattan Study, of whom 1274 had LTPA assessments at enrollment. LTPA was represented continuously as metabolic equivalent score (MET-score) and ordinally as model-based cluster analysis (LTPA-cluster), both based on the same LTPA assessments. We evaluated ECAS sonographically using carotid intima-media thickening and number of carotid plaques. ICAS was assessed with time-of-flight magnetic resonance angiograph and defined as ≥50% or ≥70% stenosis. We applied regression analyses to evaluate the association between LTPA with ECAS and ICAS, adjusting for confounders. RESULTS: Of 1274 included participants (mean age 71±9 years; 60% women; 65% Hispanic), the mean MET-score was 10±16 and 60% were in a LTPA-cluster with any activity. Among those with carotid ultrasound (n=1234), the mean carotid intima-media thickening was 0.97±0.09 mm, and 56% of participants had at least one carotid plaque identified. Among those with magnetic resonance angiograph (n=1211), 8% had ≥50% ICAS and 5% had ≥70% ICAS. For ICAS, MET-score was associated with ≥70% ICAS (adjusted odds ratio per unit increase in MET-score [95% CI, 0.97 [0.94-0.99]) but not with ECAS measures (carotid intima-media thickening, adjusted ß-estimate per unit increase in MET-score [95% CI], 0.002 [-0.003 to 0.006] or number of plaques, adjusted ß-estimate [95% CI], 0.0001 [-0.0001 to 0.0003]). Substituting MET-score with LTPA-clusters replicated the association between ≥70% ICAS and LTPA (adjusted odds ratio per each increased LTPA-cluster [95% CI], 0.83 [0.70-0.99]). CONCLUSIONS: In this diverse stroke-free population, we found LTPA most strongly associated with asymptomatic ≥70% ICAS. Given the high-risk nature of ≥70% ICAS, these findings may emphasize the role of LTPA in people at risk for ICAS.
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Estenose das Carótidas , Noma , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Constrição Patológica , Estudos Transversais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Exercício FísicoRESUMO
BACKGROUND: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma osteopontin is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD). METHODS: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n=19), Dementia/No CSVD (n=22), and Dementia+CSVD (n=21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. RESULTS: Plasma osteopontin levels were elevated in the Dementia+CSVD group (mean=70.69±39.00 ng/ml) but not in the Dementia/No CSVD group (mean=45.46±19.11 ng/ml) compared to the No dementia/No CSVD group (mean=36.43±15.72 ng/ml). Osteopontin was associated with Dementia+CSVD (Odds Ratio (OR) per ng/ml=1.06, 95%CI 1.02-1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman's rank correlation ï²=0.46, p=0.0001), but not with other components of CSVD. CONCLUSION: In this pilot, greater levels of plasma osteopontin were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions.
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OBJECTIVES: Given Mediterranean-style diet (MeDi) reduces risk of cardiovascular events, we hypothesized MeDi may also be protective against intracranial large artery stenosis (ICAS), a common cause of stroke worldwide. METHODS: This cross-sectional study included stroke-free participants of the Northern Manhattan Study, a diverse population-based study of stroke risk factors. We represented MeDi continuously (range 0-8) based on enrollment food frequency questionnaires, excluding alcohol consumption. We evaluated ICAS both dichotomously at clinically relevant stenosis severities and continuously as a score (possible range 0-44), summated from stenosis severity scores of major intracranial arteries from time-of-flight magnetic resonance angiography. We used logistic or zero-inflated Poisson regression, adjusting for key confounders. RESULTS: Among 912 included participants (mean age 64±8 years, 59% female, 65% Hispanic, mean MeDi score 4±1.5), 5% and 8% of participants had ≥50% or ≥70% ICAS, respectively (score median [interquartile range]: 0 [0-2]). Increased MeDi score was inversely associated with ICAS, but did not reach statistical significance (≥50% stenosis odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.79-1.06]; ≥70% stenosis OR [95% CI]: 0.91 [0.74-1.13]; stenosis score ß-estimate [95% CI]: -0.02 [-0.06-0.01]). CONCLUSION: In this stroke-free subsample, we did not find a significant association between MeDi and ICAS. We may have been limited by statistical power.
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Dieta Mediterrânea , Arteriosclerose Intracraniana , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Transversais , Constrição Patológica/complicações , Acidente Vascular Cerebral/etiologia , Fatores de Risco , Artérias , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Arteriosclerose Intracraniana/complicaçõesRESUMO
BACKGROUND: Intracranial large artery stenosis (ILAS) is an important contributor to ischemic stroke in the United States and worldwide. There is evidence to suggest that chronic exposure to certain infectious agents may also be associated with ILAS. We aimed to study this association further in an ethnically diverse, prospective, population-based sample of Northern Manhattan. METHODS: We enrolled a random sample of stroke-free participants from an urban, racially, and ethnically diverse community in 1993. Participants have been followed prospectively and a subset underwent brain magnetic resonance angiograms from 2003 to 2008. Intracranial stenoses of the circle of Willis and vertebrobasilar arteries were scored as 0=no stenosis, 1≤50% (or luminal irregularities), 2=50% to 69%, 3≥70% stenosis, and 4=flow gap. We summed the individual score of each artery to produce a global ILAS score (possible range, 0-44). Past infectious exposure to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2 was determined using serum antibody titers. RESULTS: Among 572 NOMAS (Northern Manhattan Study) participants (mean age 71.0±8.0 years, 60% women, 68% Hispanic) with available magnetic resonance angiogram and serological data, herpes simplex virus 2 (beta=0.051, P<0.001) and cytomegalovirus (beta=0.071, P<0.05) were associated with ILAS score after adjusting for demographics and vascular risk factors. Stratifying by anterior and posterior circulations, herpes simplex virus 2 remained associated with the anterior circulation (beta=0.055 P<0.01) but not with posterior circulation ILAS score. CONCLUSIONS: Chronic infectious exposures, specifically herpes simplex virus 2 and cytomegalovirus were associated with asymptomatic ILAS as seen on magnetic resonance angiogram imaging. This may represent an additional target of intervention in the ongoing effort to stem the substantial global burden of strokes related to ILAS.
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Noma , Acidente Vascular Cerebral , Idoso , Artérias , Estudos de Coortes , Constrição Patológica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noma/complicações , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologiaRESUMO
INTRODUCTION: Despite complete recanalization by mechanical thrombectomy, abnormal perfusion can be detected on MRI obtained post-endovascular therapy (EVT). The presence of residual perfusion abnormalities post-EVT may be associated with blood-brain barrier breakdown in response to mechanical disruption of the endothelium from multiple-pass thrombectomy. We hypothesize that multiple-pass versus single-pass thrombectomy is associated with a higher rate of residual hypoperfusion and increased lesion growth at 24 h. MATERIALS AND METHODS: For this analysis, we included patients presenting to one of two stroke centers between January 2015 and February 2018 with an acute ischemic stroke within 12 h from symptom onset if they had a large vessel occlusion of the anterior circulation documented on magnetic resonance angiography or CTA, baseline MRI pre-EVT with imaging evidence of hypoperfusion, underwent EVT, and had a post-EVT MRI with qualitatively interpretable perfusion-weighted imaging data at 24 h. MRI Tmax maps using a time delay threshold of >6 s were used to quantitate hypoperfusion volumes. Residual hypoperfusion at 24 h was solely defined as Tmax volume >10 mL with >6 s delay. Complete recanalization was defined as modified treatment in cerebral infarction visualized on angiography at EVT completion. Hyperintense acute reperfusion injury marker was assessed on post-EVT pre-contrast fluid-attenuated inversion recovery at 24 h. Major early neurological improvement was defined as a reduction of the admission National Institutes of Health Stroke Scale by ≥8 points or a score of 0-1 at 24 h. Good functional outcome was defined as 0-2 on the modified Rankin Scale on day 30 or 90. RESULTS: Fifty-five patients were included with median age 67 years, 58% female, 45% Black/African American, 36% White/Caucasian, median admission National Institutes of Health Stroke Scale 19, large vessel occlusion locations: 71% M1, 14.5% iICA, 14.5% M2, 69% treated with intravenous recombinant tissue plasminogen activator. Of these, 58% had multiple-pass thrombectomy, 39% had residual perfusion abnormalities at 24 h, and 64% had severe hyperintense acute reperfusion injury marker at 24 h. After adjusting for complete recanalization, only multiple-pass thrombectomy (odds ratio, 4.3 95% CI, 1.07-17.2; p = 0.04) was an independent predictor of residual hypoperfusion at 24 h. Patients with residual hypoperfusion had larger lesion growth on diffusion-weighted imaging (59 mL vs. 8 mL, p < 0.001), lower rate of major early neurological improvement (24% vs. 70%, p = 0.002) at 24 h, and worse long-term outcome based on the modified Rankin Scale at 30 or 90 days, 5 versus 2 (p < 0.001). CONCLUSIONS: Our findings suggest that incomplete reperfusion on post-EVT MRI is present even in some patients with successful recanalization at the time of EVT and is associated with multiple-pass thrombectomy, lesion growth, and worse outcome. Future studies are needed to investigate whether patients with residual hypoperfusion may benefit from immediate adjunctive therapy to limit lesion growth and improve clinical outcome.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Traumatismo por Reperfusão , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Progressão da Doença , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Reperfusão , Estudos Retrospectivos , Trombectomia/efeitos adversos , Trombectomia/métodos , Ativador de Plasminogênio Tecidual , Resultado do TratamentoRESUMO
INTRODUCTION: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. METHODS: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aß)40 and Aß42 , total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517). RESULTS: Over 3.8 years, there were no significant between-group differences for Aß40, Aß42, Aß42 /Aß40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL. DISCUSSION: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062.
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Doença de Alzheimer , Disfunção Cognitiva , Peptídeos beta-Amiloides , Biomarcadores , Pressão Sanguínea , Humanos , Filamentos Intermediários , Proteínas tauRESUMO
OBJECTIVE: To determine whether immune protein panels add significant information to correlates of cognition. BACKGROUND: Immune mechanisms in vascular cognitive aging are incompletely characterized. DESIGN/METHODS: A subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers. RESULTS: Among 1179 participants (mean age 70 ± 8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test < 0.005 for all domains). C-C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging. CONCLUSIONS: Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.
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Cognição , Idoso , Biomarcadores , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos ProspectivosRESUMO
INTRODUCTION: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time. MATERIALS AND METHODS: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity. RESULTS: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008). CONCLUSIONS: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.
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AVC Isquêmico , Terapia Trombolítica , Administração Intravenosa , Imagem de Difusão por Ressonância Magnética , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Resultado do TratamentoRESUMO
Race/ethnic minorities face significant inequities in stroke incidence, prevalence, care, and outcomes. The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving symposium, a collaborative initiative of the American Heart Association and National Institute of Neurological Disorders and Stroke, was the first-ever annual multidisciplinary scientific forum focused on race/ethnic inequities in cerebrovascular disease, with the overarching goal of reducing inequities in stroke and accelerating the translation of research findings to improve outcomes for race/ethnic minorities. The symposium featured esteemed invited plenary speakers, lecturing on determinants of race/ethnic inequities in stroke and interventions aimed at redressing the inequities. The Edgar J. Kenton III Award recognized Ralph Sacco, MD, MS, for his lifetime contributions to investigation, management, mentorship, and community service in the field of stroke inequities. Early career investigators were provided with travel awards to attend the symposium; presented their research at moderated poster and Think Tank sessions; received career development advice at the Building Momentum session; and networked with experienced stroke inequities researchers. Future conferences-The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving 2021 to 2024-will broaden the focus to include 5 major persistent inequities (race/ethnic, sex, geographic, socioeconomic, and global). Each year will focus on a different theme (community and stakeholder engagement; clinical trials; implementation science; and policy and dissemination). By fostering a community of stroke inequities researchers, we hope to highlight promising work, illuminate research gaps, facilitate networking, inform policy makers, recognize achievement, inspire greater interest among junior investigators to pursue careers in this field, and provide networking opportunities for underrepresented minority scientists.
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Congressos como Assunto , Equidade em Saúde , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Acidente Vascular Cerebral/etnologia , Negro ou Afro-Americano , Hispânico ou Latino , Humanos , Acidente Vascular Cerebral/terapia , População BrancaRESUMO
Background and Purpose- Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods- Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results- The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions (P for interaction<0.05). Relative to those with DBP 90+ mm Hg, participants with DBP <80 mm Hg had 13% lower WMHV in the frontal lobe (95% CI, -21% to -3%), 11% lower WMHV in the parietal lobe (95% CI, -19% to -1%), 22% lower WMHV in the anterior periventricular region (95% CI, -30% to -14%), and 16% lower WMHV in the posterior periventricular region (95% CI, -24% to -6%). Participants with DBP 80 to 89 mm Hg also exhibited about 12% (95% CI, -20% to -3%) lower WMHV in the anterior periventricular region and 9% (95% CI, -18% to -0.4%) lower WMHV in the posterior periventricular region, relative to participants with DBP 90≥ mm Hg. Post hoc pairwise t tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown-adjusted P<0.05). Systolic blood pressure was not strongly related to regional WMHV. Conclusions- Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.
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Pressão Sanguínea , Diástole , Hipertensão/fisiopatologia , Substância Branca/diagnóstico por imagem , Idoso , Pressão Arterial , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Estudos Prospectivos , Sístole , Lobo Temporal/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Background and Purpose- To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods- We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results- At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8-0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1-0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3-3.7]) and vascular death (hazard ratio, 2.24 [1.29-3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions- CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.
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Infarto Encefálico/patologia , Isquemia Encefálica/patologia , Infarto Cerebral/classificação , Infarto/patologia , Acidente Vascular Cerebral/patologia , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Infarto Encefálico/complicações , Isquemia Encefálica/etiologia , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Feminino , Humanos , Infarto/diagnóstico , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
OBJECTIVE: There is limited information on factors influencing cognitive decline in rural settings from low- and middle-income countries. Using the Atahualpa Project cohort, we aimed to assess the burden of cognitive decline in older adults living in a rural Ecuadorian village. METHODS: The study included Atahualpa residents aged greater than or equal to 60 years who had a follow-up Montreal Cognitive Assessment (MoCA) repeated at least 1 year after baseline. MoCA decline was assessed by multivariable longitudinal linear models, adjusted for demographics, days between MoCA tests, cardiovascular risk factors, and neuroimaging signatures of structural brain damage. RESULTS: We included 252 individuals who contributed 923.7 person-years of follow-up (mean: 3.7 ± 0.7 years). The mean baseline MoCA was 19.5 ± 4.5 points, and the follow-up MoCA was 18.1 ± 4.9 points (P = 0.001). Overall, 154 individuals (61%) had lower MoCA scores at follow-up. The best fitted longitudinal linear model showed a decline of follow-up MoCA from baseline (ß: 0.14; 95% CI, 0.0-0.21; P < 0.001). High glucose levels, global cortical atrophy, and white matter hyperintensities were independently and significantly associated with greater MoCA decline. CONCLUSION: This study provides evidence of cognitive decline in older adults living in a rural setting. Main targets for prevention should include glucose control and the control of factors that are deleterious for the development of cortical atrophy and white matter hyperintensities.
Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/diagnóstico por imagem , Córtex Cerebral/patologia , Cognição , Equador/epidemiologia , Feminino , Humanos , Vida Independente/psicologia , Modelos Lineares , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Neuroimagem , Estudos Prospectivos , Fatores de Risco , População RuralRESUMO
Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.
Assuntos
Anestesia/efeitos adversos , Encéfalo/fisiopatologia , Transtornos Cognitivos/terapia , Delírio do Despertar/terapia , Idoso , Idoso de 80 Anos ou mais , Anestesiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/prevenção & controle , Delírio do Despertar/fisiopatologia , Delírio do Despertar/prevenção & controle , Nível de Saúde , Humanos , Fatores de RiscoRESUMO
Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]). Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.
Assuntos
Anti-Hipertensivos/uso terapêutico , Encéfalo/fisiologia , Hipertensão/tratamento farmacológico , Substância Branca/patologia , Idoso , Pressão Sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de RiscoRESUMO
Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.