MRI Substudy Research Articles

Abstract WP423: Adiponectin and Components of Metabolic Syndrome are Associated With Cortical Thickness: The Northern Manhattan Study

Objective: Examine the association of adiponectin and metabolic syndrome components with measures of global and lobar cortical thickness. Background: Metabolic syndrome has been associated with structural brain changes, but the relationship of adiponectin and cortical thickness is understudied. Methods: The Northern Manhattan Study MRI Sub-Study is a mostly Hispanic, stroke-free, prospective cohort study of older adults. Cortical thickness (mm) was obtained from T1-weighted brain MRIs using the publically-available Freesurfer software. Regional cortical thickness metrics were averaged to obtain mean lobar cortical thickness. Adiponectin (μg/mL) was measured at baseline (1993-2001). Metabolic syndrome components were measured at MRI Sub-Study baseline (2003-2008). We estimated the cross-sectional associations of adiponectin (per 1 SD) and metabolic syndrome components with global and lobar cortical thickness (per 1 SD) using multivariable linear regression models adjusted for sociodemographic factors, APOE ε4 allele presence, and health-related behaviors. All hypothesis testing was two-sided with an alpha level of 5%. Results: Freesurfer data were available in 947 participants (mean±SD age=70±9 years, 63% women, 66% Hispanics, 16% black, and 15% white). Global cortical thickness was normally distributed (mean±SD = 2.3±0.1mm). In fully adjusted models, 1 SD (4.9μg/mL) increase in adiponectin was associated with smaller overall (β [95%CI] = -0.07 [-0.14, -0.0002]) and parietal cortical thickness (β [95%CI] = -0.08 [-0.03, -0.0002]). Greater blood glucose levels significantly associated with smaller occipital cortical thickness (β [95%CI] = -0.003 [-0.006, -0.0007]). Greater waist circumference was significantly associated with smaller frontal cortical thickness (β [95%CI] = -0.02 [-0.04, -0.0007]). Neither blood pressure (systolic and diastolic) nor cholesterol (total, HDL-C, and LDL-C) were associated with global or regional cortical thickness. Conclusions: There was heterogeneity in the cross-sectional associations between adiponectin, metabolic syndrome components, and regional cortical thickness. Further studies are needed to explore the temporal relationship between risk factors and cortical thinning.

Associations of plasma clusterin and Alzheimer's disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study.

BackgroundClinical and epidemiological studies of older persons have implicated clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community.Materials and methodsSubjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison.ResultsIn multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD.ConclusionsIn middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.

White matter microstructure, white matter lesions, and hypertension: An examination of early surrogate markers of vascular-related brain change in midlife.

ObjectiveWe examined imaging surrogates of white matter microstructural abnormalities which may precede white matter lesions (WML) and represent a relevant marker of cerebrovascular injury in adults in midlife.MethodsIn 698 community-dwelling adults (mean age 50 years ±3.5 SD) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study, WML were identified on structural MR and fractional anisotropy (FA), representing WM microstructural integrity, was derived using Diffusion Tensor Imaging. FA and WML maps were overlaid on a parcellated T1-template, based on an expert-delineated brain atlas, which included 42 WM tract ROIs. Analyses occurred in stages: 1) WML were quantified for the different tracts (i.e., frequency, volume, volume relative to tract size); 2) the interdependence of FA in normal appearing WM (NAWM) and WML was examined across tracts; 3) associations of NAWM FA and hypertension status were assessed controlling for WML volume. In the latter analysis, both overall hypertension (i.e. hypertension vs. normotension and prehypertension vs. normotension) and hypertension categorized by antihypertensive treatment status (yes/no) and blood pressure control (e.g., diastolic <90 mmHg, systolic <140 mmHg), were assessed.ResultsWML were widely distributed across different WM tracts, however, WML volume was small. Mean NAWM FA was lower in participants with vs. participants without WML in given tracts. Hypertension was significantly associated with lower mean NAWM FA globally across tracts, both before and after adjustment for WML volume. Moreover, the magnitude of this association differed by treatment status and the level of control of the hypertension.ConclusionsIn middle-aged adults, NAWM FA could represent a relevant marker of cerebrovascular injury when WML are minimally present.

Modulation of GLP-1 Levels by a Genetic Variant That Regulates the Cardiovascular Effects of Intensive Glycemic Control in ACCORD.

OBJECTIVEA genome-wide association study in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922 and rs9299870) that were significantly associated with cardiovascular mortality during intensive glycemic control and could potentially be used, when combined into a genetic risk score (GRS), to identify patients with diabetes likely to derive benefit from intensive control rather than harm. The aim of this study was to gain insights into the pathways involved in the modulatory effect of these variants.RESEARCH DESIGN AND METHODSFasting levels of 65 biomarkers were measured at baseline and at 12 months of follow-up in the ACCORD-Memory in Diabetes (ACCORD-MIND) MRI substudy (n = 562). Using linear regression models, we tested the association of the GRS with baseline and 12-month biomarker levels, and with their difference (Δ), among white subjects, with genotype data (n = 351) stratified by intervention arm.RESULTSA significant association was observed between GRS and ΔGLP-1 (glucagon-like peptide 1, active) in the intensive arm (P = 3 × 10−4). This effect was driven by rs57922 (P = 5 × 10−4). C/C homozygotes, who had been found to derive cardiovascular benefits from intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By contrast, T/T homozygotes, who had been found to experience increased cardiac mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No association between ΔGLP-1 and GRS or rs57922 was observed in the standard treatment arm.CONCLUSIONSDifferences in GLP-1 axis activation may mediate the modulatory effect of variant rs57922 on the cardiovascular response to intensive glycemic control. These findings highlight the importance of GLP-1 as a cardioprotective factor.

Lack of association of MRI determined subclinical cardiovascular disease with dizziness and vertigo in a cross-sectional population-based study.

ObjectiveWe investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample.MethodsData from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the “Kooperative Gesundheitsforschung in der Region Augsburg” (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided.ResultsLifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo.However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5).ConclusionsIn this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes.

Physical Inactivity Predicts Slow Gait Speed in an Elderly Multi-Ethnic Cohort Study: The Northern Manhattan Study

Introduction: Gait speed is associated with multiple adverse outcomes of aging. We hypothesized that physical inactivity would be prospectively inversely associated with gait speed independently of white matter hyperintensity volume and silent brain infarcts on MRI. Methods: Participants in the Northern Manhattan Study MRI sub-study had physical activity assessed when they were enrolled into the study. A mean of 5 years after the MRI, participants had gait speed measured via a timed 5-meter walk test. Physical inactivity was defined as reporting no leisure-time physical activity. Multi-variable logistic and quantile regression was performed to examine the associations between physical inactivity and future gait speed adjusted for confounders. Results: Among 711 participants with MRI and gait speed measures (62% women, 71% Hispanic, mean age 74.1 ± 8.4), the mean gait speed was 1.02 ± 0.26 m/s. Physical inactivity was associated with a greater odds of gait speed in the lowest quartile (<0.85 m/s, adjusted OR 1.90, 95% CI 1.17-3.08), and in quantile regression with 0.06 m/s slower gait speed at the lowest 20 percentile (p = 0.005). Conclusions: Physical inactivity is associated with slower gait speed independently of osteoarthritis, grip strength, and subclinical ischemic brain injury. Modifying sedentary behavior poses a target for interventions aimed at reducing decline in mobility.

Cardiovascular health in young adulthood and structural brain MRI in midlife: The CARDIA study.

To examine the association between the American Heart Association (AHA) Life's Simple 7 (LS7) metric and brain structure. We determined cardiovascular health (CVH) according to the AHA LS7, assigning 0, 1, or 2 points for meeting poor, intermediate, or ideal criteria for the 7 components (range 0-14) at baseline (aged 18-30 years in 1985-1986) and year 25 follow-up examination for 518 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) brain MRI substudy. Visit-based CVH score and average score was assessed in relation to percent of intracranial volume of normal tissue of the whole brain, gray matter, and white matter, and abnormal tissue volume of white matter at year 25 using multivariable linear, logistic, and quantile regression, after adjustment for age, sex, race, field center, educational attainment, and alcohol consumption. Mean percentage of whole brain volume, normal gray matter, and normal white matter was 81.3% (±2.5), 42.9% (±2.0), and 38.4% (±2.0). Greater CVH score at baseline (per each additional point at year 0: 0.1%, 95% confidence limits 0.01-0.3; p < 0.05) and average CVH score were associated with greater percentage of whole brain volume (per each additional point in average score: 0.2%, 95% confidence limits 0.04-0.3; p < 0.05). Visit-based or average CVH score was not significantly associated with normal gray or white matter volume or abnormal white matter volume. Maintaining ideal levels of cardiovascular health, determined by the LS7, in young adulthood is associated with greater whole brain volume in middle age but not regional differences in structure.

Association between MRI-derived hepatic fat fraction and blood pressure in participants without history of cardiovascular disease.

We assessed whether liver fat content, as determined by MRI, correlates with blood pressure (BP), a major vascular risk factor, in individuals from the general population without history of stroke and coronary or peripheral artery disease. Cross-sectional data from 384 participants (161 women; aged 39-73 years) of a MRI substudy of the KORA FF4 survey were used. Hepatic fat fraction (HFF) was measured in the left and right lobe of the liver using single voxel multiecho H-spectroscopy and at the level of the portal vein using a multiecho Dixon-sequence. Associations of HFF with SBP and DBP as well as hypertension were assessed by right censored normal regression (accounting for antihypertensive treatment) and by logistic regression, respectively. High levels of HFF measured on the level of the portal vein (90th percentile, 21.8%), compared with low HFF levels (10th percentile, 1.7%), were associated with higher SBP (131 vs. 122 mmHg; overall P = 0.001), higher DBP (82 vs. 76 mmHg, P < 0.001) and with higher odds of hypertension [odds ratio (OR) = 2.16, P = 0.025]. A level of 5.13% (54th percentile) was identified as optimal HFF cut-off for the prediction of hypertension (OR = 2.00, P = 0.015). Alcohol consumption emerged as an effect modifier for the association between HFF and hypertension (nonalcohol drinker: OR = 3.76, P = 0.025; alcohol drinker: OR = 1.59, P = 0.165). MRI-derived subclinical HFF is associated with SBP and DBP as well as with hypertension in participants from the general population without history of cardiovascular disease.

Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis

PurposeWe assessed whether MRI measures of synovitis, osteitis and bone erosion were associated with patient-reported outcomes (PROs) in a longitudinal clinical trial setting among patients with rheumatoid arthritis (RA).MethodsThis longitudinal...

The Relationship Between Brain MR Spectroscopy and Disability in Multiple Sclerosis: 20-Year Data from the U.S. Glatiramer Acetate Extension Study.

ABSTRACTBACKGROUND AND PURPOSEConventional MRI techniques do not necessarily provide information about multiple sclerosis (MS) disease pathology or progression. Nonconventional MRI techniques, including proton magnetic resonance spectroscopy (1H‐MRS), are increasingly used to improve the qualitative and quantitative specificity of MR images. This study explores potential correlations between MRI measures of disease and disability progression as measured by the Expanded Disability Status Scale (EDSS), Functional Systems (FS), and ambulation index scores in a unique cohort of MS patients treated with glatiramer acetate that has been closely monitored for over 20 years.METHODSThis was a multicenter, open‐label, cross‐sectional MRI substudy among participants in the GA‐9004 open‐label extension of the 36‐month, double‐blind GA‐9001 study, timed to coincide with the prospectively planned 20‐year clinical exam.RESULTSOf 64 patients who participated in the MRI substudy, results are presented for the 39 patients (61%) who had a 1H‐MRS assessment at 20 years of treatment. Both total N‐acetylaspartate relative to total creatinine (tNAA/tCr) concentration ratio and T1 lesion volume were found to be robustly associated with disability levels with different statistical approaches. Gray matter (GM) volume was found to be a more consistent parameter than white matter (WM) volume for disability allocation. The elastic net algorithm showed a trade‐off between WM and GM volumes for disability estimation when different disability definitions were used.CONCLUSIONSAmong patients with MS receiving long‐term glatiramer acetate therapy, consistent effects on disability levels indicated by EDSS and pyramidal FS score thresholds were found for tNAA/tCr concentration ratio and T1 lesion volume.

Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study.

Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β = -0.231 ± 0.112, p = 0.040) and episodic memory (β = -0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.

Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) – a network implicated in AD and other brain disorders – in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=−0.063, 95% CI: −0.106, −0.020), anterior cingulate (β=−0.055, 95% CI: −0.101, −0.010), and medial frontal lobe (β=−0.050, 95% CI: −0.092, −0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=−0.024, 95% CI: −0.062, 0.014) and the hippocampus (β=−0.006, 95% CI: −0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.

Elevated blood pressure, cerebrovascular reactivity, and the default-mode brain network: Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI Sub-Study (P1.088)

Elevated blood pressure, cerebrovascular reactivity, and the default-mode brain network: Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI Sub-Study (P1.088)

Insights into Relationships Between Serum Ferritin and Liver Iron Concentration Trends during 12 Months of Iron Chelation Therapy with Deferasirox – a Post-Hoc Analysis from the Epic Study

▪BackgroundSerum ferritin is regularly used to assess response to chelation therapy and correlates significantly with liver iron concentration (LIC) particularly when LIC is <7 mg Fe/g dry weight (dw) and serum ferritin is <4000 ng/mL. The absence of a serum ferritin decrease in the first months of a new chelation regime may be interpreted as a lack of response with respect to decreasing body iron load. However, sequential LIC determination (where available) has indicated that many of these patients do indeed have a decrease in LIC. This clinical experience requires greater understanding, particularly the nature of the LIC and serum ferritin relationship at baseline serum ferritin values ≥4000 ng/mL.The aim of this post-hoc analysis of the EPIC study was to gain insight into the relationship between serum ferritin and LIC in response to deferasirox over 1 year, in a large patient cohort, so that serum ferritin trends can be more clearly interpreted and evidence-based practical guidance be given for patients with transfusion-dependent thalassemia (TDT).MethodsTDT patients were recruited from 25 sites, received 1-year of deferasirox treatment and had serum ferritin and R2 magnetic resonance imaging (R2-MRI)-assessed LIC measurements at baseline and 1 year. Summary statistics are provided for serum ferritin and LIC responders (decrease, any change from baseline <0) and nonresponders (increase or no change, any change from baseline ≥0), and for baseline serum ferritin categories (≥4000 vs <4000 ng/mL).ResultsOf the 374 patients analyzed in the EPIC liver MRI substudy, 317 had TDT, of which 72.7% (n=226) had a serum ferritin response and 27.3% (n=85) had no response. Importantly, after 1 year LIC decreased in approximately half of serum ferritin nonresponders (51.8%; n=44; Table) and in 79.6% of serum ferritin responders (n=180). Median (min, Q1, Q3, max) change in LIC (mg Fe/g dw) was –5.4 (–38.5, –11.7, –0.9, 15.4) in serum ferritin responders and –0.2 (–18.4, –2.6, 2.7, 19.6) in nonresponders. Median (range) transfusional iron intake (mg/kg/day) was similar in serum ferritin responders (0.30 [0.01–1.49]) and nonresponders (0.37 [0.02–1.00]). Median deferasirox dose (mg/kg/day) was higher in serum ferritin responders than nonresponders (28.1 [9.8–40.4] vs 23.7 [9.7–37.9]).Evaluation of responses by baseline serum ferritin showed that a greater proportion of serum ferritin responders with baseline serum ferritin <4000 ng/mL also had decreased LIC (88.7% [n=102]; Table), compared with serum ferritin responders with baseline serum ferritin ≥4000 ng/mL (70.3% [n=78]). However, serum ferritin baseline category had no effect on the proportion of patients who decreased LIC despite having no serum ferritin response (52.6% [n=30], <4000 ng/mL; 50.0% [n=14], ≥4000 ng/mL; Table). There was little change in median LIC in serum ferritin nonresponders after 1 year regardless of baseline serum ferritin value (–0.3 [–13.5–18.7] for <4000 ng/mL and 0.2 [–18.4–19.6] for ≥4000 ng/mL).Assessment by change in serum ferritin and LIC quadrants indicated that patients without serum ferritin or LIC response had the lowest baseline median (range) serum ferritin and LIC (2155 [480–9725] ng/mL; 11.9 [1.8–37.5] mg Fe/g dw; n=41), and received a lower median deferasirox dose (23.7 [9.7–36.0] mg/kg/day). Overall, median LIC decrease (mg Fe/g dw) was smaller in patients with baseline serum ferritin <4000 ng/mL (n=172) than in those with serum ferritin ≥4000 ng/mL (–2.8 [–38.5–18.7] vs –4.9 [–31.1–19.6]; n=139). Median iron intake was similar between groups.Discussion and conclusionsA decrease in LIC was seen in ~80% of serum ferritin responders after 1 year of deferasirox; a greater proportion of serum ferritin responders (88%) decreased LIC when baseline serum ferritin was <4000 ng/mL. Importantly, among patients with no serum ferritin response up to half may be responding with respect to iron balance, indicating that a lack of serum ferritin response should be interpreted with caution. However, since a decrease in serum ferritin predicts a decrease in LIC in 80% of patients, MRI measurement (where available) should be prioritized for patients with serum ferritin increase/no change. Overall, serum ferritin response can help predict LIC response, but in some patients treated with deferasirox, serum ferritin may not accurately reflect removal of iron from the body. [Display omitted] DisclosuresPorter:Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy; Cerus: Membership on an entity’s Board of Directors or advisory committees; Alnylam: Membership on an entity’s Board of Directors or advisory committees. Taher:Novartis: Honoraria, Research Funding. Sutcharitchan:Novartis: Research Funding. Aydinok:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chakravarty:Novartis: Employment. El-Ali:Novartis: Employment.

The COgnitive-Pulmonary Disease (COgnitive-PD) study: protocol of a longitudinal observational comparative study on neuropsychological functioning of patients with COPD

IntroductionIntact cognitive functioning is necessary for patients with chronic obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle guidelines, to make informed decisions and subsequently act on it....

The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy

ObjectiveTo examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI.MethodsIn a substudy of a randomised, double-blind, phase...

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy

Carotid artery stenting (CAS) is associated with a higher risk of both hemodynamic depression and new ischemic brain lesions on diffusion-weighted imaging than carotid endarterectomy (CEA). We assessed whether the occurrence of hemodynamic depression is associated with these lesions in patients with symptomatic carotid stenosis treated by CAS or CEA in the randomized International Carotid Stenting Study (ICSS)-MRI substudy. The number and total volume of new ischemic lesions on diffusion-weighted imaging 1 to 3 days after CAS or CEA was measured in the ICSS-MRI substudy. Hemodynamic depression was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The number of new ischemic lesions was the primary outcome measure. We calculated risk ratios and 95% confidence intervals per treatment with Poisson regression comparing the number of lesions in patients with or without hemodynamic depression. A total of 229 patients were included (122 allocated CAS; 107 CEA). After CAS, patients with hemodynamic depression had a mean of 13 new diffusion-weighted imaging lesions, compared with a mean of 4 in those without hemodynamic depression (risk ratio, 3.36; 95% confidence interval, 1.73-6.50). The number of lesions after CEA was too small for reliable analysis. Lesion volumes did not differ between patients with or without hemodynamic depression. In patients treated by CAS, periprocedural hemodynamic depression is associated with an excess of new ischemic lesions on diffusion-weighted imaging. The findings support the hypothesis that hypoperfusion increases the susceptibility of the brain to embolism. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470.

Total cerebral blood flow and mortality in old age

To examine the association of total cerebral blood flow (CBF) with all-cause, noncardiovascular, and cardiovascular mortality in older subjects at risk of cardiovascular disease. We included 411 subjects with a mean age of 74.5 years from the MRI substudy of the Prospective Study of Pravastatin in the Elderly at Risk. Total CBF was measured at baseline, and occurrence of death was recorded in an average follow-up period of 11.8 years. For each participant, total CBF was standardized for brain parenchymal volume. Cox regression models were used to estimate risk of all-cause, noncardiovascular, and cardiovascular mortality in relation to CBF. Mortality rates among participants in low, middle, and high thirds of total CBF were 52.1, 41.5, and 28.7 per 1,000 person-years, respectively. Compared with participants in the high third of CBF, participants in the low third had 1.88-fold (95% confidence interval [CI]: 1.30-2.72) higher risk of all-cause mortality, 1.66-fold (95% CI: 1.06-2.59) higher risk of noncardiovascular mortality, and 2.50-fold (95% CI: 1.28-4.91) higher risk of cardiovascular mortality. Likewise, compared with participants in the high third of CBF, participants in the middle third had 1.44-fold (95% CI: 0.98-2.11) higher risk of all-cause mortality, 1.29-fold (95% CI: 0.82-2.04) higher risk of noncardiovascular mortality, and 1.86-fold (95% CI: 0.93-3.74) higher risk of cardiovascular mortality. These associations were independent of prevalent vascular status and risk factors. Low total CBF is linked with higher risk of all-cause, noncardiovascular, and cardiovascular mortality in older people independent of clinical cardiovascular status.

Abstract TP47: Infarct Growth Does Not Predict Functional Outcome For Small Vessel Stroke

Introduction: Infarct growth has been shown to be a predictor of clinical outcome following ischemic stroke and has been used as a surrogate in reperfusion studies. There are no data whether the association of infarct growth and clinical outcome depends on stroke etiology. Furthermore, there is uncertainty on how to handle small volume infarcts with some studies excluding them from analyses. We studied the relationship between infarct growth and functional outcome in stroke patients with small volume infarcts for subgroups with small and non-small vessel etiologies. Methods: We studied 37 patients in the MRI substudy of the Efficacy of Nitric Oxide in Stroke (ENOS) trial with baseline infarct volumes of ≤5ml. None of the patients were treated with reperfusion strategies. Brain MRI was performed serially at baseline within 48 hours of onset, on days 7 and 90. Infarct growth was measured as the volume difference between final T2 and baseline DWI lesions. Good functional outcome was defined as day 90 modified Rankin score ≤2 and poor as &gt;2. Results: Among the 26 patients with underlying small vessel etiology, there was no difference between those with good and poor outcomes in terms of absolute [median 0.0 (IQR -0.4 to 1.1) vs 0.1 (-0.7 to 0.2) mL, p=0.802] and relative infarct growth [median -3 (-27 to 81) vs 8 (-46 to 10) %, p=0.802]. However, in the 11 patients with etiologies other than small vessel disease, patients with good outcome had less absolute [median -0.9 (-1.6 to 0.7) vs 3.2 (0.2 to 9.1) mL, p=0.033] and relative infarct growth [median -59 (-81 to 9) vs 154 (35 to 292) %, p=0.019] compared to those with poor outcome. Discussion: In small volume strokes, infarct growth was not associated with functional outcome for small vessel stroke although there was a significant association for other stroke etiologies. This novel finding in this small sample should be confirmed in larger studies. Our findings are expected as small vessel stroke involves occlusion of penetrating arterioles which supply small, limited yet strategically important brain regions. Thus, while infarct growth may be a suitable surrogate for clinical outcomes for small volume infarcts due to non-small vessel disease, but it may not be for small vessel strokes.