Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.

BACKGROUND: Little is known about incidence of vascular and Alzheimer's dementias in American Indians. METHODS We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64-95 years from 11 tribes across 3 states, with neurological examinations, 1.5T magnetic resonance imaging (MRI), and extensive cognitive testing. Visit 1 in 2010-2013 (n=817) and Visit 2 in 2017-2019 (n=403) included all willing, surviving participants. Standardized cognitive tests at both visits included Modified Mini Mental Status Examination (3MSE), Wechsler Adult Intelligence Scale digit symbol coding (WAIS), Controlled Oral Word Association fas (COWA), California Verbal Learning Test short form (CVLT). Test materials added at follow-up included Wide Range Achievement (reading) Test (WRAT) and National Alzheimer's Coordinating Center Uniform Data Set cognitive battery (v3 form C2) , including Montreal Cognitive Assessment (MoCA). MRI neuroradiologists coded infarcts, hemorrhages, white matter hyperintensities, sulcal atrophy, and ventricle enlargement. RESULTS Mean time between exams was 6.7 years (SD 1.1, range 3.8-9.1). Years of formal education had modest correlation with WRAT reading score (r=0.45). Prevalence and incidence of infarcts were (respectively) 32% and 12.8/1000 person-years (PY); hemmorhages 6% and 4.4/1000 PY; worsening sulci 74% and 19.0/1000 PY; wosening ventricle 79% and 30.1/1000 PY; worsening leukoaraiosis 44% and 26.1/1000 PY. Linear losses per year in cognitive scores were 0.6% 3MSE, 1.2% WAIS, 0.6% COWA, 2.2% CVLT. Mean MoCA scores were 18.9 (SD 4.3). DISCUSSION These are the first data on longitudinal cognitive and imaging changes in American Indians, as well as first reports of AD related features. Mean scores in MoCA were similar or lower than standard cutoffs used to diagnose dementia in other racial/ethnic groups, suggesting that standardized cognitive tests may not perform well in this population. Test validation, adaptation, and score adjustment are warranted. Years of education was a poor proxy for premorbid function, suggesting novel methods for cognitive score contextualization is also needed in this population. Evaluation of selective survival suggests attrition from death and frailty should be accounted for in causal analyses. Overall, these data represent a unique opportunity to examine neurology topics of critical importance to an understudied population.

The ability of magnetic resonance black blood vessel wall imaging to evaluate blunt cerebrovascular injury following acute trauma.

BACKGROUND AND PURPOSE: Blunt cerebrovascular injury (BCVI) is associated with a significant risk of ischemic stroke when left untreated. Cross-sectional imaging is vital to early BCVI diagnosis and treatment; however, conventional luminal vessel imaging is limited in its ability to evaluate for vessel wall pathology. The purpose of this study is to evaluate the ability of vessel wall magnetic resonance imaging (VWI) to detect and evaluate BCVI in acutely injured trauma patients relative to neck computed tomographic angiography (CTA). MATERIALS AND METHODS: Trauma patients with suspected BCVI on initial neck CTA were prospectively recruited for VWI evaluation. Two neuroradiologists blinded to patient clinical history and CTA findings evaluated each artery independently on VWI and noted the presence and grade of BCVI. These results were subsequently compared to neck CTA findings relative to expert clinical consensus review. Interrater reliability of VWI for detecting BCVI was evaluated using a weighted Cohen κ-statistic. RESULTS: Ten trauma patients (40 cervical arteries) were prospectively evaluated using both CTA and VWI. Out of 18 vascular lesions identified as suspicious for BCVI on CTA, six lesions were determined to represent true BCVI by expert consensus review. There was almost perfect agreement between VWI and expert consensus regarding the presence and grade of BCVI (κ=0.82). This agreement increased when considering only low grade BCVI. There was only fair agreement between CTA and expert clinical consensus (κ=0.36). This agreement decreased when considering only low grade BCVI. CONCLUSIONS: VWI can potentially accurately identify and evaluate BCVI in acutely injured trauma patients with excellent inter-rater reliability.

Inter-rater and scan-rescan reproducibility of the detection of intracranial atherosclerosis on contrast-enhanced 3D vessel wall MRI.

OBJECTIVE: The objective is to establish interscan, inter- and intra-rater reproducibility of a multicontrast three-dimensional contrast-enhanced intracranial vessel wall (IVW) MRI protocol with 0.6 mm acquired (0.3 mm interpolated) isotropic resolution in the detection of intracranial atherosclerosis. METHODS: Subjects with established intracranial atherosclerosis were prospectively recruited and underwent two contrast-enhanced three-dimensional IVW scans within a 2-week period. Four raters with varying degrees of vessel wall imaging interpretation experience, through an iterative training process developed guidelines for plaque identification with no, possible and definite plaque categories. Using these guidelines, the raters reviewed the cases in pairs (consensus rating), while blinded to the interpretations of the other pair, clinical reports and patient history. The rater pairs reviewed 19 segments per patient for the presence and location of atherosclerotic plaques. Inter-scan, inter rater and intra rater reproducibility were assessed. RESULTS: 19 subjects were scanned twice, with 361 total segments reviewed and 304-324 evaluable segments analyzed in the different reproducibility assessments. Overall inter-rater agreement for possible and definite plaque was 88.9 % [κ = 0.73; 95% confidence interval (CI) (0.62-0.81)], inter-scan/intra-rater agreement was 82.1 % [κ = 0.58; 95% CI (0.48-0.70)] and inter-scan/inter-rater agreement of 84.5% [κ = 0.64; 95% CI (0.51 - 0.76)]. CONCLUSION: Contrast-enhanced IVW imaging, with the utilization of detailed plaque definition guidelines for image review, can be a reproducible technique for the evaluation of intracranial atherosclerosis. ADVANCES IN KNOWLEDGE: This work is the first to establish reproducibility of IVW for plaque identification with and without contrast. Reproducibility using contrast is important as most IVW applications rely on lesion enhancement.

Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up.

OBJECTIVE: To examine the association between neuroimaging features in a predominantly middle-aged cohort and risk of late-life dementia. METHODS: Cerebral MRI was performed on 1,881 individuals with no history of stroke from the Atherosclerosis Risk in Communities Study cohort in 1993 to 1995. White matter hyperintensities (WMH), ventricular size, and sulcal size were graded on a semiquantitative scale, and presence of silent cerebral infarcts was identified. In 2011 to 2013, dementia was determined from neuropsychological testing, informant interview, hospital ICD-9 codes, and death certificate dementia codes. Cox regression was used to evaluate associations between MRI findings and dementia. RESULTS: Over 20 years of follow-up, dementia developed in 279 participants (14.8%). High-grade WMH and high-grade ventricular size were independently associated with increased dementia risk (hazard ratio [HR] for WMH 1.62, 95% confidence interval [CI] 1.14-2.30; HR for ventricular size 1.46, 95% CI 1.06-2.03). There was an increased risk of dementia for diabetic participants with silent infarcts (HR 2.56, 95% CI 1.23-5.31) but not among nondiabetic participants (HR 0.87, 95% CI 0.56-1.37). Each 1-unit increase in the total number of high-grade cerebral abnormalities at baseline (count values range 0-4) showed increased dementia risk, with a considerably higher risk among diabetic participants (HR for diabetes mellitus 1.97, 95% CI 1.44-2.69; HR for no diabetes mellitus 1.20, 95% CI 1.03-1.39). CONCLUSION: In adults without evidence of clinical stroke, MRI-detected WMH and ventricular enlargement in midlife may represent markers of brain injury that increase risk for later-life cognitive impairment. The presence of diabetes mellitus may modify the association between silent infarcts and dementia.

Added Value of Vessel Wall Magnetic Resonance Imaging for Differentiation of Nonocclusive Intracranial Vasculopathies.

BACKGROUND AND PURPOSE: Our goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal imaging alone. METHODS: We retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathies: atherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases. RESULTS: Thirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8% versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (κ=0.72) and only slight agreement for luminal imaging (κ=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (κ=0.69 versus 0.18; P<0.001). CONCLUSIONS: IVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.

Left Ventricular Mass, Brain Magnetic Resonance Imaging, and Cognitive Performance: Results From the Strong Heart Study.

Left ventricular mass (LVM) has been shown to serve as a measure of target organ damage resulting from chronic exposure to several risk factors. Data on the association of midlife LVM with later cognitive performance are sparse. We studied 721 adults (mean age 56 years at baseline) enrolled in the Strong Heart Study (SHS, 1993-1995) and the ancillary CDCAI (Cerebrovascular Disease and Its Consequences in American Indians) Study (2010-2013), a study population with high prevalence of cardiovascular disease. LVM was assessed with transthoracic echocardiography at baseline in 1993 to 1995. Cranial magnetic resonance imaging and cognitive testing were undertaken between 2010 and 2013. Generalized estimating equations were used to model associations between LVM and later imaging and cognition outcomes. The mean follow-up period was 17 years. A difference of 25 g in higher LVM was associated with marginally lower hippocampal volume (0.01%; 95% confidence interval, 0.02-0.00; P=0.001) and higher white matter grade (0.10; 95% confidence interval, 0.02-0.18; P=0.014). Functionally, participants with higher LVM tended to have slightly lower scores on the modified mini-mental state examination (0.58; 95% confidence interval, 1.08-0.08; P=0.024). The main results persisted after adjusting for blood pressure levels or vascular disease. The small overall effect sizes are partly explained by survival bias because of the high prevalence of cardiovascular disease in our population. Our findings emphasize the role of cardiovascular health in midlife as a target for the prevention of deleterious cognitive and functional outcomes in later life.

Total Brain and Hippocampal Volumes and Cognition in Older American Indians: The Strong Heart Study.

BACKGROUND: Estimates of hippocampal volume by magnetic resonance imaging have clinical and cognitive correlations and can assist in early Alzheimer disease diagnosis. However, little is known about the relationship between global or regional brain volumes and cognitive test performance in American Indians. MATERIALS AND METHODS: American Indian participants (N=698; median age, 72 y) recruited for the Cerebrovascular Disease and its Consequences in American Indians study, an ancillary study of the Strong Heart Study cohort, were enrolled. Linear regression models assessed the relationship between magnetic resonance imaging brain volumes (total brain and hippocampi) and cognitive measures of verbal learning and recall, processing speed, verbal fluency, and global cognition. RESULTS: After controlling for demographic and clinical factors, all volumetric measurements were positively associated with processing speed. Total brain volume was also positively associated with verbal learning, but not with verbal recall. Conversely, left hippocampal volume was associated with both verbal learning and recall. The relationship between hippocampal volume and recall performance was more pronounced among those with lower scores on a global cognitive measure. Controlling for APOE ε4 did not substantively affect the associations. CONCLUSIONS: These results support further investigation into the relationship between structural Alzheimer disease biomarkers, cognition, genetics, and vascular risk factors in aging American Indians.

Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study.

BACKGROUND: The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. METHODS: Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. RESULTS: The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. CONCLUSIONS: Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population.

White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.

BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. RESULTS: A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. CONCLUSIONS: Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.

Setting a gold standard for quantification of leukoaraiosis burden in patients with ischemic stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Accurate and reliable measurement of leukoaraiosis, or MR-detected white, matter hyper-intensity (WMH) burden in subjects with acute ischemic stroke (AIS) is important for, ongoing research studies and future models of risk and outcome prediction, but the presence of a, cerebral infarct may complicate measurement. We sought to assess accuracy of a volumetric method, designed to measure WMH in AIS subjects as compared to the previously validated protocol. NEW METHOD: We randomly selected and equally sampled 120 brain scans from the Atherosclerosis, Risk in Communities (ARIC) MRI Study individuals within designated mild, moderate, and severe, tertiles of WMH volume (WMHV). T2 FLAIR axial images were analyzed using the AIS WMH volumetric, protocol and compared with the ARIC (gold standard) method. Pearson correlation coefficients, linear, concordance correlation coefficient, and Blant­Altman procedures were used to assess measurement, agreements between the two procedures. RESULTS: Median WMHV determined by using the ARIC method was 7.8 cm3 (IQR 5.7­13.55) vs. 3.54 cm3, (IQR 2.1­7.2) using the AIS WMH method. There was good correlation between the two measurements, (r = 0.52, 0.67, and 0.9 for tertiles 1, 2, and 3 respectively) (p < 0.001). COMPARISON WITH EXISTING METHOD: The AIS WMH protocol was specific for leukoaraiosis in ischemic, stroke, but it appeared to underestimate WMHV compared to the gold standard method. CONCLUSIONS: Estimates of MR-detectable WMH burden using a volumetric protocol designed for, analysis of clinical scans correlate strongly with gold standard measurements. These findings will, facilitate future studies of WMH in normal aging and in patients with stroke and other cerebrovascular, disease.

Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium.

OBJECTIVE: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. METHODS: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. RESULTS: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). INTERPRETATION: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.

Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study.

Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993-1995, and returned for a repeat magnetic resonance imaging examination in 2004-2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42-5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56-6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66-4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39-4.40) and white matter lesion incidence (odds ratio 2.12; 95% confidence interval: 1.18-3.81) and progression (odds ratio 2.22; 95% confidence interval: 1.00-5.88). In conclusion, retinal microvascular abnormalities are associated with emergence of subclinical magnetic resonance imaging brain infarcts and white matter lesions, independent of shared risk factors. Retinal vascular imaging may offer a non-invasive tool to investigate the pathogenesis and natural history of cerebral small-vessel disease.

Retinal microvascular signs and 10-year risk of cerebral atrophy: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Cerebral atrophy, detected as ventricular enlargement or sulcal widening on MRI, is recognized as a risk factor for vascular dementia or Alzheimer disease. However, its underlying pathophysiology is not known. We examined whether retinal microvascular assessment could provide predictive information on the risk of ventricular enlargement and sulcal widening on MRI. METHODS: A prospective, population-based study was conducted of 810 middle-aged persons without clinical stroke or MRI infarcts. All participants had a first cranial MRI and retinal photography in 1993 to 1995 and returned for a repeated MRI in 2004 to 2006 (median follow-up of 10.5 years). Retinal photographs were graded for presence of retinopathy and retinal microvascular abnormalities, and MRI images were graded for ventricular size and sulcal size according to standardized protocols. Ventricular enlargement and sulcal widening were defined as an increase in ventricular size or sulcal size of >or=3 of 10 grades between baseline and follow-up. RESULTS: After adjusting for age, gender, and cardiovascular risk factors, retinopathy and arteriovenous nicking at baseline were associated with 10-year ventricular enlargement (OR and 95% CI: 2.03, 1.20 to 4.42 for retinopathy and 2.19, 1.23 to 3.90 for arteriovenous nicking). Retinal signs were not associated with 10-year sulcal widening. CONCLUSIONS: Retinopathy and arteriovenous nicking are predictive of long-term risk of ventricular enlargement, but not of sulcal widening, independent of cardiovascular risk factors. These data support a microvascular etiology for subcortical but not cortical cerebral atrophy.

Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from the CHARGE Consortium.

BACKGROUND AND PURPOSE: Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed cross-sectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had >or=1 MRI infarct). RESULTS: The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P=4.64x10(-7)). Highly suggestive associations (P<1.0x10(-5)) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r(2)>0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. CONCLUSIONS: This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed.

Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Blood pressure (BP) is a predictor of concurrent and subsequently measured white-matter hyperintensity (WMH), but longitudinal studies of WMH changes and data in black participants are lacking. We hypothesized that WMH progression would be (1) strongly related to BP in blacks and whites and (2) predicted more strongly by earlier (midlife) or cumulative BP measurements than by measures at older ages. METHODS: Participants were 983 individuals (49% black) from the Atherosclerosis Risk in Communities (ARIC) Study who underwent cerebral magnetic resonance imaging in 1993-1995 and 2004-2006. Associations between BP (measured at each of 5 visits, in addition to a time-averaged cumulative BP) and progression of WMHs were analyzed and compared. RESULTS: Cumulative systolic BP (SBP) was the strongest BP predictor of WMH progression in adjusted models. Higher cumulative SBP (by 20 mm Hg) was associated with greater progression of WMHs and was similar in blacks (2.5 cm(3), P<0.0001) and whites (2.6 cm(3), P<0.0001). Higher cumulative SBP (per 20 mm Hg) was also associated with being in the top quintile of WMH progression (adjusted odds ratio=2.0; 95% CI, 1.6 to 2.6). Earlier SBP measurements were stronger predictors of WMH progression than were later SBP measurements, but in blacks only. CONCLUSIONS: In this population-based cohort, cumulative SBP was a stronger predictor of WMH progression than SBP from individual visits, in both blacks and whites. Earlier BPs were stronger predictors than BPs measured at later time points in blacks only.

Interrater reliability in assessing quality of diagnostic accuracy studies using the QUADAS tool. A preliminary assessment.

RATIONALE AND OBJECTIVES: Quality Assessment of Diagnostic Accuracy Studies (QUADAS) is a new tool to measure the methodological quality of diagnostic accuracy studies in systematic reviews. We used data from a systematic review of magnetic resonance spectroscopy (MRS) in the characterization of suspected brain tumors to provide a preliminary evaluation of the inter-rater reliability of QUADAS. MATERIALS AND METHODS: A structured literature search identified 19 diagnostic accuracy studies. These publications were distributed randomly to primary and secondary reviewers for dual independent assessment. Reviewers recorded methodological quality by using QUADAS on a custom-designed spreadsheet. We calculated correlation, percentage of agreement, and kappa statistic to assess inter-rater reliability. RESULTS: Most studies in our review were judged to have used an accurate reference standard. Conversely, the MRS literature frequently failed to specify the length of time between index and reference tests or that the clinicians were unaware of the index test findings when reporting the reference standard. There was good correlation (rho = 0.78) between reviewers in assessment of the overall number of quality criteria met. However, mean agreement for individual QUADAS questions was only fair (kappa = 0.22) and ranged from no agreement beyond chance (kappa < 0) to moderate agreement (kappa = 0.58). CONCLUSION: Inter-rater reliability in our study was relatively low. Nevertheless, we believe that QUADAS potentially is a useful tool for highlighting the strengths and weaknesses of existing diagnostic accuracy studies. Low reliability suggests that different reviewers will reach different conclusions if QUADAS is used to exclude "low-quality" articles from meta-analyses. We discuss methods for improving the validity and reliability of QUADAS.

Temporal lobe perfusion in the deaf: MR measurement with pulsed arterial spin labeling (FAIR).

RATIONALE AND OBJECTIVES: Experimental studies in animals have shown that loss of a primary sensory modality early in life may result in substantial alterations in cortical organization. This study was performed to measure cerebral perfusion in auditory cortex in congenitally deaf adults using the FAIR (Flow-sensitive Alternating Inversion Recovery) magnetic resonance imaging technique. Our hypothesis was that there would be relatively intact perfusion in auditory cortex. MATERIALS AND METHODS: Twenty-six profoundly congenitally deaf subjects were compared with 15 control subjects. A FAIR perfusion slice was scanned through the superior temporal gyrus parallel to the Sylvian fissure while subjects were at rest. Perfusion maps were calculated and regions of interest were drawn over the superior temporal gyrus including auditory cortex and the medial occipital lobe. RESULTS: The relative perfusion of the superior temporal gyrus (STG) was slightly less in the deaf (right STG = 0 .79 +/- 0.16, left = 0.93 +/- 0.29) compared with the hearing (right STG = 0.90 +/- 0.14, left = 0.98 +/- 0.31) when normalized to the occipital cortex, but the differences were not statistically significant. Both showed moderate left lateralization; however, only in the deaf did this reach statistical significance (P < .01). CONCLUSIONS: In the resting state, the deaf demonstrate a relatively normal perfusion in the region of cortex usually associated with auditory function. Although the presumed underlying electrical activity may represent some degree of residual auditory function, it is likely that the normal level of perfusion reflects cortical reorganization and the early migration of nonauditory processing into this area.

Bilateral Sudden Hearing Loss in Waldenstrom's Macroglobulinemia: MR Appearance.

A 46 year-old man with acquired immunodeficiency syndrome presented with sudden development of vertigo and tinnitus and then simultaneous, bilateral, profound, sudden hearing loss. Magnetic resonance imaging showed bilateral high signal within the cochlea, vestibule, and portions of the semicircular canals on the non-enhanced T1-weighted images, most consistent with recent hemorrhage into the otic labyrinth. Serum analysis and bone-marrow biopsy led to diagnosis of Waldenstrom's macroglobulinemia - a likely cause of the presumed hemorrhage.