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Background and Objectives: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts., Methods: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates., Results: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ 2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient β = 0.020; SE = 0.009; p = 0.03)., Discussion: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

Objectives: This study investigated video eye tracking (VET) in comatose patients with traumatic brain injury (TBI)., Methods: We recruited healthy participants and unresponsive patients with TBI. We surveyed the patients' clinicians on whether the patient was tracking and performed the Coma Recovery Scale-Revised (CRS-R). We recorded eye movements in response to motion of a finger, a face, a mirror, and an optokinetic stimulus using VET glasses. Patients were classified as covert tracking (tracking on VET alone) and overt tracking (VET and clinical examination). The ability to obey commands was evaluated at 6-month follow-up., Results: We recruited 20 healthy participants and 10 patients with TBI. The use of VET was feasible in all participants and patients. Two patients demonstrated covert tracking (CRS-R of 6 and 8), 2 demonstrated overt tracking (CRS-R of 22 and 11), and 6 patients had no tracking (CRS-R of 8, 6, 5, 7, 6, and 7). Five of 56 (9%) tracking assessments were missed on clinical examination. All patients with tracking recovered consciousness at follow-up, whereas only 2 of 6 patients without tracking recovered at follow-up., Discussion: VET is a feasible method to measure covert tracking. Future studies are needed to confirm the prognostic value of covert tracking., (© 2023 American Academy of Neurology.)

Background and Objectives: While chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age." We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes., Methods: We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input., Results: We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p -values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes., Discussion: T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke., (© 2022 American Academy of Neurology.)

Background and Objectives: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways., Methods: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age 2 , sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts., Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location., Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions., (© 2022 American Academy of Neurology.)

Background and Objectives: Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear., Methods: We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease-MRI-based CMBs and autopsy-based CAA-as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55-90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples., Results: We included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (β = 4.49 ± 1.13, p = 0.04) and white matter (β = 4.72 ± 2.1, p = 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (β = 5.17 ± 2.47, p = 0.04) than in those with ≥2 CMBs (β = 1.97 ± 3.41, p = 0.56). In BARS, CAA was associated with increased cortical thickness (β = 6.5 ± 2.3, p = 0.016) but not with increased brain weight (β = 1.54 ± 1.29, p = 0.26)., Discussion: Superficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease., (© 2022 American Academy of Neurology.)

Background and Objectives: Early consciousness disorder (ECD) after acute ischemic stroke (AIS) is understudied. ECD may influence outcomes and the decision to withhold or withdraw life-sustaining treatment., Methods: We studied patients with AIS from 2010 to 2019 across 122 hospitals participating in the Florida Stroke Registry. We studied the effect of ECD on in-hospital mortality, withholding or withdrawal of life-sustaining treatment (WLST), ambulation status on discharge, hospital length of stay, and discharge disposition., Results: Of 238,989 patients with AIS, 32,861 (14%) had ECD at stroke presentation. Overall, average age was 72 years (Q1 61, Q3 82), 49% were women, 63% were White, 18% were Black, and 14% were Hispanic. Compared to patients without ECD, patients with ECD were older (77 vs 72 years), were more often female (54% vs 48%), had more comorbidities, had greater stroke severity as assessed by the National Institutes of Health Stroke Scale (score ≥5 49% vs 27%), had higher WLST rates (21% vs 6%), and had greater in-hospital mortality (9% vs 3%). Using adjusted models accounting for basic characteristics, patients with ECD had greater in-hospital mortality (odds ratio [OR] 2.23, 95% CI 1.98-2.51), had longer hospitalization (OR 1.37, 95% CI 1.33-1.44), were less likely to be discharged home or to rehabilitation (OR 0.54, 95% CI 0.52-0.57), and were less likely to ambulate independently (OR 0.61, 95% CI 0.57-0.64). WLST significantly mediated the effect of ECD on mortality (mediation effect 265; 95% CI 217-314). In temporal trend analysis, we found a significant decrease in early WLST (<2 days) (R 2 0.7, p = 0.002) and an increase in late WLST (≥2 days) (R 2 0.7, p = 0.004)., Discussion: In this large prospective multicenter stroke registry, patients with AIS presenting with ECD had greater mortality and worse discharge outcomes. Mortality was largely influenced by the WLST decision., (© 2022 American Academy of Neurology.)

Objective: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS)., Methods: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes., Results: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm 3 (interquartile range 2.18-14.61 cm 3 ) and differed significantly across CCS subtypes ( p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus ( p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes ( p < 0.001)., Conclusion: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke., (© 2020 American Academy of Neurology.)

Objective: To examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging., Methods: We analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity., Results: On average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] -0.089 [-0.153, -0.025], WC β [95% CI] -0.103 [-0.169, -0.037]) in fully adjusted models. Similarly, compared to those with BMI <25, obese participants (BMI ≥30) exhibited smaller cortical thickness (β [95% CI] -0.207 [-0.374, -0.041]). These associations were particularly evident for those aged <65 years. Similar but weaker associations were observed for TCV. Most associations with WMHV and SBI did not reach statistical significance., Conclusions: Adiposity in early-old age is related to reduced global gray matter later in life in this diverse sample. Future studies are warranted to elucidate causal relationships and explore region-specific associations., (© 2019 American Academy of Neurology.)

Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts., Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI., Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 -8 ; and LINC00539/ZDHHC20, p = 5.82 × 10 -9 . Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( p value for BI, p [BI] = 9.38 × 10 -25 ; p [SSBI] = 5.23 × 10 -14 for hypertension), smoking ( p [BI] = 4.4 × 10 -10 ; p [SSBI] = 1.2 × 10 -4 ), diabetes ( p [BI] = 1.7 × 10 -8 ; p [SSBI] = 2.8 × 10 -3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 -18 ; p [SSBI] = 2.3 × 10 -7 ), stroke ( p [BI] = 3.9 × 10 -69 ; p [SSBI] = 3.2 × 10 -24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 -157 ; p [SSBI] = 3.16 × 10 -106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( p ≤ 0.0022), without indication of directional pleiotropy., Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD)., Methods: Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included., Results: High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses., Conclusions: High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD., (© 2018 American Academy of Neurology.)

Objective: To evaluate trends in prevalence of cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and drug abuse) and cardiovascular diseases (carotid stenosis, chronic renal failure [CRF], and coronary artery disease [CAD]) in acute ischemic stroke (AIS) in the United States., Methods: We used the 2004-2014 National Inpatient Sample to compute weighted prevalence of each risk factor in hospitalized patients with AIS and used joinpoint regression to evaluate change in prevalence over time., Results: Across the 2004-2014 period, 92.5% of patients with AIS had ≥1 risk factor. Overall age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively, while those of carotid stenosis, CRF, and CAD were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age (hypertension: 44% in 18-39 years vs 82% in 60-79 years), race (diabetes: Hispanic 49% vs white 30%), and sex (drug abuse: men 3% vs women 1.4%). Using joinpoint regression, prevalence of hypertension increased annually by 1.4%, diabetes by 2%, dyslipidemia by 7%, smoking by 5%, and drug abuse by 7%. Prevalence of CRF, carotid stenosis, and CAD increased annually by 13%, 6%, and 1%, respectively. Proportion of patients with multiple risk factors also increased over time., Conclusions: Despite numerous guidelines and prevention initiatives, prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in AIS increased across the 2004-2014 period. Proportion of patients with carotid stenosis, CRF, and multiple risk factors also increased. Enhanced risk factor modification strategies and implementation of evidence-based recommendations are needed for optimal stroke prevention., (© 2017 American Academy of Neurology.)

Objective: Since arterial stiffness is a functional measure of arterial compliance and may be an important marker of cerebrovascular disease, we examined the association of carotid artery stiffness with white matter hyperintensity volume (WMHV) in a cross-sectional study of 1,166 stroke-free participants., Methods: Carotid beta stiffness index (STIFF) was assessed by M-mode ultrasound of the common carotid artery and calculated as the ratio of natural log of the difference between systolic and diastolic blood pressure over STRAIN, a ratio of the difference between carotid systolic and diastolic diameter (DD) divided by DD. WMHV was measured by fluid-attenuated inversion recovery MRI. The associations of STIFF, DD, and STRAIN with WMHV were examined using linear regression after adjusting for sociodemographic, lifestyle, and vascular risk factors., Results: In a fully adjusted model, larger carotid DD was significantly associated with greater log-WMHV (β = 0.09, p = 0.001). STIFF and STRAIN were not significantly associated with WMHV. In adjusted analyses stratified by race-ethnicity, STRAIN (β = -1.78, p = 0.002) and DD (β = 0.11, p = 0.001) were both associated with greater log-WMHV among Hispanic participants, but not among black or white participants., Conclusions: Large carotid artery diameters are associated with greater burden of white matter hyperintensity (WMH) in this multiethnic population. The association between increased diameters, decreased STRAIN, and greater WMH burden is more pronounced among Hispanics. These associations suggest a potential important pathophysiologic role of extracranial large artery remodeling in the burden of WMH., (© 2017 American Academy of Neurology.)

Objective: To examine frequent snoring, sleepiness, and sleep duration with baseline and longitudinal performance on neuropsychological (NP) battery., Methods: The analysis consists of 711 participants of the Northern Manhattan Study (NOMAS) with sleep data and NP assessment (age 63 ± 8 years, 62% women, 18% white, 17% black, 67% Hispanic) and 687 with repeat NP testing (at a mean of 6 ± 2 years). The main exposures were snoring, sleepiness, and sleep duration obtained during annual follow-up. Using factor analysis-derived domain-specific Z scores for episodic memory, language, executive function, and processing speed, we constructed multivariable regression models to evaluate sleep symptoms with baseline NP performance and change in performance in each NP domain., Results: In the cross-sectional analysis, adjusting for demographics and the NOMAS vascular risk score, participants with frequent snoring had worse executive function (β = -12; p = 0.04) and processing speed (β = -13; p = 0.02), but no difference in with episodic memory or language. Those with severe daytime sleepiness (β = -26; p = 0.009) had worse executive function, but no changes in the other NP domains. There was no cross-sectional association between sleep duration and NP performance. Frequent snoring (β = -29; p = 0.0007), severe daytime sleepiness (β = -29; p = 0.05), and long sleep duration (β = -29; p = 0.04) predicted decline in executive function, adjusting for demographic characteristics and NOMAS vascular risk score. Sleep symptoms did not explain change in episodic memory, language, or processing speed., Conclusions: In this race-ethnically diverse community-based cohort, sleep symptoms led to worse cognitive performance and predicted decline in executive function., (© 2016 American Academy of Neurology.)

Objective: To examine the association between migraine and stroke/vascular outcomes in a racially/ethnically diverse, older cohort., Methods: Participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders, second edition. We estimated the association between migraine and combined vascular events including stroke and stroke only over a mean follow-up of 11 years, using Cox models adjusted for sociodemographic and vascular risk factors., Results: Of 1,292 participants (mean age 68 ± 9 years) with migraine data followed prospectively for vascular events, 262 patients (20%) had migraine and 75 (6%) had migraine with aura. No association was found between migraine (with or without aura) and risk of either stroke or combined cardiovascular events. There was an interaction between migraine and current smoking (p = 0.02 in relation to stroke and p = 0.03 for combined vascular events), such that those with migraine and smoking were at an increased risk. The hazard ratio of stroke for migraine among current smokers was 3.17 (95% confidence interval [CI] 1.13-8.85) and among current nonsmokers was 0.77 (95% CI 0.44-1.35). In relation to combined vascular events, the hazard ratio for migraine vs no migraine among current smokers was 1.83 (95% CI 0.89-3.75) and among current nonsmokers was 0.63 (95% CI 0.43-0.94)., Conclusion: In our racially/ethnically diverse population-based cohort, migraine was associated with an increased risk of stroke among active smokers but not among nonsmokers., (© 2015 American Academy of Neurology.)

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population., Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates., Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function., Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance., (© 2015 American Academy of Neurology.)

Objective: We evaluated the association between obstructive sleep apnea (OSA) and neurocognitive function among community-dwelling Hispanic/Latino individuals in the United States., Methods: Cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos middle-aged and older adults, aged 45 to 74 years, with neurocognitive test scores at baseline measurements from 2008 to 2011. Neurocognitive scores were measured using the Word Fluency (WF) Test, the Brief-Spanish English Verbal Learning Test (SEVLT), and the Digit Symbol Substitution (DSS) Test. OSA was defined by the apnea-hypopnea index (AHI). Multivariable linear regression models were fit to evaluate relations between OSA and neurocognitive scores., Results: The analysis consisted of 8,059 participants, mean age of 56 years, 55% women, and 41% with less than high school education. The mean AHI was 9.0 (range 0-142; normal AHI <5/h). There was an association between the AHI and all 4 neurocognitive test scores: Brief-SEVLT-sum (β = -0.022) and -recall (β = -0.010), WF (β = -0.023), and DSS (β = -0.050) at p < 0.01 that was fully attenuated by age. In the fully adjusted regression model, female sex was a moderating factor between the AHI and WF (β = -0.027, p < 0.10), SVELT-sum (β = -0.37), SVELT-recall (β = -0.010), and DSS (β = -0.061) at p < 0.01., Conclusion: OSA was associated with worse neurocognitive function in a representative sample of Hispanic/Latino women in the United States., (© 2014 American Academy of Neurology.)

Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems., Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems., Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54-0.58)., Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner., (© 2014 American Academy of Neurology.)