Vascular risk factors and longitudinal changes on brain MRI: the ARIC study.
Ontology highlight
ABSTRACT: Objective
To evaluate associations between vascular risk factors and changes in burden of infarcts, ventricular size (VS), sulcal widening (SW), and white matter hyperintensities (WMH) in an initially middle-aged, biracial cohort from the Atherosclerosis Risk in Communities (ARIC) study.Methods
Initial brain magnetic resonance (MR) scans and evaluations for vascular risk factors were performed in 1,812 ARIC participants in 1994-1995. In 2004-2006, 1,130 ARIC participants underwent repeat MR scans. MR scans were rated using a validated 9-point scale for VS, SW, and WMH. Infarcts were recorded. Multiple logistic regression analysis was used to assess associations between vascular risk factors and change between MR scans of one or more grades in VS, SW, WMH, or appearance of new infarcts, controlling for age, sex, and race.Results
At baseline, the 1,112 participants with usable scans (385 black women, 200 black men, 304 white women, 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models, diabetes at baseline was associated with incident infarcts (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.29-2.95) and worsening SW (OR 2.10, 95% CI 1.36-3.24). Hypertension at baseline was associated with incident infarcts (OR 1.73, 95% CI 1.23-2.42). In subjects with the highest tertile of fasting blood sugar and systolic blood pressure at baseline, the risk of incident infarcts was 3.68 times higher (95% CI 1.89-7.19) than those in the lowest tertile for both.Conclusion
Both atrophic and ischemic imaging changes were driven by altered glycemic and blood pressure control beginning in midlife.
SUBMITTER: Knopman DS
PROVIDER: S-EPMC3115812 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundA growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation.ObjectiveWe tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years.MethodsIncluded in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (≥15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, ≥8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias.ResultsAt the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes.ConclusionsIn this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.
| S-EPMC4944966 | biostudies-literature
Project description:AimsSeveral factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age.Methods and resultsAssociations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.ConclusionHigher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.
| S-EPMC6642726 | biostudies-literature
Project description:ObjectiveTo identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).DesignCross-sectional brain Magnetic Resonance I (MRI) study.SettingCommunity based cohort in three U.S. sites.ParticipantsA Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.Primary and secondary outcomes3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.ResultsAdjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).ConclusionIn middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.
| S-EPMC4374951 | biostudies-literature
Project description:ObjectivesIn this cross-sectional study, we tested the construct validity of a "total SVD score," which combines individual MRI features of small-vessel disease (SVD) in one measure, by testing associations with vascular risk factors and stroke subtype.MethodsWe analyzed data from patients with lacunar or nondisabling cortical stroke from 2 prospective stroke studies. Brain MRI was rated for the presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces independently. The presence of each SVD feature was summed in an ordinal "SVD score" (range 0-4). We tested associations with vascular risk factors, stroke subtype, and cerebral atrophy using ordinal regression analysis.ResultsIn 461 patients, multivariable analysis found that age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.08-1.12), male sex (OR 1.58, 95% CI 1.10-2.29), hypertension (OR 1.50, 95% CI 1.02-2.20), smoking (OR 2.81, 95% CI 1.59-3.63), and lacunar stroke subtype (OR 2.45, 95% CI 1.70-3.54) were significantly and independently associated with the total SVD score. The score was not associated with cerebral atrophy.ConclusionsThe total SVD score may provide a more complete estimate of the full impact of SVD on the brain, in a simple and pragmatic way. It could have potential for patient or risk stratification or early efficacy assessment in clinical trials of interventions to prevent SVD progression and may (after further testing) have a useful role in clinical practice.
| S-EPMC4180484 | biostudies-literature
Project description:PurposeTo examine progressive brain changes associated with chronic fatigue syndrome (CFS).Materials and methodsWe investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1- and T2-weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.ResultsWe found a significant decrease in WM volumes in the left inferior fronto-occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, PFWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (PFWE < 0.05) and decreased GM and blood volumes in contralateral regions (PFWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (PFWE < 0.05).ConclusionThe results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301-1311.
| S-EPMC5111735 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Some recent studies in older, largely white populations suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition, but such results may be affected by reverse causation. Measuring 25(OH)D in late middle age before poor cognition affects behavior may provide clearer results. METHODS:This was a prospective cohort analysis of 1652 participants (52% white, 48% black) in the Atherosclerosis Risk in Communities (ARIC) Brain MRI Study. 25(OH)D was measured from serum collected in 1993-1995. Cognition was measured by the delayed word recall test (DWRT), the digit symbol substitution test (DSST) and the word fluency test (WFT). Dementia hospitalization was defined by ICD-9 codes. Adjusted linear, logistic and Cox proportional hazards models were used. RESULTS:Mean age of participants was 62 years and 60% were female. Mean 25(OH)D was higher in whites than blacks (25.5 vs. 17.3 ng/ml, P < 0.001). Lower 25(OH)D was not associated with lower baseline scores or with greater DWRT, DSST or WFT decline over a median of 3 or 10 years of follow-up (P > 0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. Although not statistically significant, lower levels of 25(OH)D were suggestive of an association with increased dementia risk [hazard ratio for lowest versus highest race-specific tertile: whites 1.32 (95% confidence interval 0.69, 2.55); blacks 1.53 (95% confidence interval 0.84, 2.79)]. CONCLUSIONS:In contrast to prior studies performed in older white populations, our study of late middle age white and black participants did not find significant associations between lower levels of 25(OH)D with lower cognitive test scores at baseline, change in scores over time or dementia risk.
| S-EPMC4114998 | biostudies-literature
Project description:Background Associations between subtle changes in cardiac and cerebral structure and function are not well understood, with some studies suggesting that subclinical cardiac changes may be associated with markers of vascular brain insult. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) Study (5th ARIC visit; 2011-2013; N=1974) were used to explore relationships between abnormalities of cardiac structure/function and subclinical brain disease and to test specific associations between those cardiac and vascular brain changes that share a common mechanism. In adjusted models white matter hyperintensities were 0.66 cm3 greater (95% confidence interval [CI] 0.08-1.25) for every 1-mm increase in left ventricular LV wall thickness and 0.64 cm3 greater (95% CI 0.19-1.08) for every 10 g/m2 increase in LV mass index, both markers of LV structure. Odds of brain infarction also increased with greater LV wall thickness (odds ratio 1.11, 95% CI 1.01-1.23 per 1 mm) and larger LV mass (odds ratio 1.08, 95% CI 1.00-1.17 per 10 g/m2). Higher ejection fraction (per 5%), a marker of systolic function, was significantly associated with decreased odds of overall infarct (odds ratio 0.85, 95% CI 0.77-0.95), but not with cortical infarction (odds ratio 0.92, 95% CI 0.78-1.08). Conclusions Among elderly participants in a large cohort study, subclinical markers of LV structure and LV systolic dysfunction were associated with increased odds of brain infarction and more white matter hyperintensities, independent of other vascular risk factors. This suggests end-organ dysfunction occurs in the heart and brain in parallel, with further studies needed to determine causality.
| S-EPMC6405621 | biostudies-literature
Project description:OBJECTIVE:To determine whether hospitalization is associated with subsequent cognitive decline or changes on brain MRI in a community-based cohort. METHODS:Baseline and follow-up cognitive testing (n = 2,386) and MRI scans with standardized assessments (n = 885) were available from a subset of white and black participants in the Atherosclerosis Risk in Communities study. Cognitive tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Hospitalization characteristics were determined using ICD-9 codes. Regression models adjusted for demographics, education, comorbidities, and APOE ?4 were used to estimate the independent association of hospitalization with changes in cognition or neuroimaging. RESULTS:Over a mean 14.1 years between visits, 1,266 participants (53.1%) were hospitalized. Hospitalization compared with no hospitalization was associated with greater decline in DSST scores (1.25 points greater decline, p < 0.001) but no difference in DWRT or WFT score change. Each additional hospitalization, as well as a critical illness vs noncritical illness hospitalization, was associated with greater decline in DSST scores. A subset of participants (n = 885) underwent MRI scans separated by 10.5 years. Hospitalization (n = 392) compared with no hospitalization was associated with a 57% higher odds of increasing ventricular size at follow-up. Each additional hospitalization, as well as having a critical illness vs noncritical illness hospitalization, and having a hospitalization with major surgery vs no surgery was associated with greater odds of increased ventricular size. CONCLUSIONS:Cognitive decline and neuroimaging changes may occur after hospitalization, independent of baseline demographics and comorbidities.
| S-EPMC4395884 | biostudies-literature
Project description:ObjectiveTo investigate the associations between lifestyle and vascular risk factors and changes in Alzheimer's disease (AD) biomarkers (beta-amyloid load via 11C-PiB PET, glucose metabolism via 18F-FDG PET and neurodegeneration via structural MRI) and global cognition in middle-aged asymptomatic participants at risk for AD.DesignProspective, longitudinal.SettingThe study was conducted at New York University Langone/Weill Cornell Medical Centres in New York City.ParticipantsSeventy cognitively normal participants from multiple community sources, aged 30-60 years with lifestyle measures (diet, intellectual activity and physical activity), vascular risk measures and two imaging biomarkers visits over at least 2 years, were included in the study.Outcome measuresWe examined MRI-based cortical thickness, fluoro-deoxy-glucose (FDG) glucose metabolism and PiB beta-amyloid in AD-vulnerable regions. A global cognitive z-score served as our summary cognition measure. We used regression change models to investigate the associations of clinical, lifestyle and vascular risk measures with changes in AD biomarkers and global cognition.ResultsDiet influenced changes in glucose metabolism, but not amyloid or cortical thickness changes. With and without accounting for demographic measures, vascular risk and baseline FDG measures, lower adherence to a Mediterranean-style diet was associated with faster rates of FDG decline in the posterior cingulate cortex (p≤0.05) and marginally in the frontal cortex (p=0.07). None of the other lifestyle variables or vascular measures showed associations with AD biomarker changes. Higher baseline plasma homocysteine was associated with faster rates of decline in global cognition, with and without accounting for lifestyle and biomarker measures (p=0.048). None of the lifestyle variables were associated with cognition.ConclusionsDiet influenced brain glucose metabolism in middle-aged participants, while plasma homocysteine explained variability in cognitive performance. These findings suggest that these modifiable risk factors affect AD risk through different pathways and support further investigation of risk reduction strategies in midlife.
| S-EPMC6254410 | biostudies-literature
Project description:ObjectiveTo examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.Research design and methodsCross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ?6.5%] <7.0% vs. ?7.0%), with further stratification by diabetes duration (<10 vs. ?10 years).ResultsIn adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ?7.0% had smaller total brain volume (? -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ?7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (?10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).ConclusionsMore-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.
| S-EPMC5652590 | biostudies-literature