Stroke Incidence and Survival in American Indians, Blacks, and Whites: The Strong Heart Study and Atherosclerosis Risk in Communities Study

Background: American Indians (AIs) have high stroke morbidity and mortality. We compared stroke incidence and mortality in AIs, blacks, and whites. Methods and Results: Pooled data from 2 cardiovascular disease cohort studies included 3182 AIs from the SHS (Strong Heart Study), aged 45 to 74 years at baseline (1988–1990) and 3765 blacks and 10 413 whites from the ARIC (Atherosclerosis Risk in Communities) Study, aged 45 to 64 years at baseline (1987–1989). Stroke surveillance was based on self-report, hospital records, and death certificates. We estimated hazard ratios for incident stroke (ischemic and hemorrhagic combined) through 2008, stratified by sex and birth-year tertile, and relative risk for poststroke mortality. Incident strokes numbered 282 for AIs, 416 for blacks, and 613 for whites. For women and men, stroke incidence among AIs was similar to or lower than blacks and higher than whites. Covariate adjustment resulted in lower hazard ratios for most comparisons, but results for these models were not always statistically significant. After covariate adjustment, AI women and men had higher 30-day poststroke mortality than blacks (relative risk=2.1 [95% CI=1.0, 3.2] and 2.2 [95% CI=1.3, 3.1], respectively), and whites (relative risk=1.6 [95% CI=0.8, 2.5] and 1.7 [95% CI=1.1, 2.4]), and higher 1-year mortality (relative risk range=1.3–1.5 for all comparisons). Conclusions: Stroke incidence in AIs was lower than for blacks and higher than for whites; differences were larger for blacks and smaller for whites after covariate adjustment. Poststroke mortality was higher in AIs than blacks and whites

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk. Methods and Results: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026). Conclusion: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Slower gait, slower information processing and smaller prefrontal area in older adults.

Item does not contain fulltextBACKGROUND: Slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests. HYPOTHESIS: We hypothesise that slower information processing explains this association, while tests of language or memory will not. METHODS: Data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index). RESULTS: In linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association. CONCLUSIONS: We conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.1 januari 201

Adjudication of Transient Ischemic Attack and Stroke in the Multi-Ethnic Study of Atherosclerosis

Background: To describe adjudication of transient ischemic attack (TIA) and stroke in an observational study. Methods: We detail the process used to adjudicate TIA and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA), a large longitudinal cohort study. Two of three vascular neurologists adjudicated each event using specific protocols. We examined the initial agreement, effect of imaging on diagnosis of TIA versus ischemic stroke, and effect of strict and less strict criteria on the number of ischemic stroke subtypes classified as undetermined. Results: Of 573 adjudicated events over 13.5 years of follow-up, 95 (16.5%) had TIA and 269 (47.0%) had stroke: 211 (78.4%) ischemic, 43 (16.0%) hemorrhagic, and 15 (5.6%) other. Disagreements occurred on 16% of initial adjudication of events. Using results from imaging, the number with TIA decreased by 8.6% and with ischemic stroke increased by 4.1%. Using less strict criteria to classify ischemic stroke subtypes reduced the number classified as undetermined, from 137 to 59, and numbers classified as cardioembolic and small vessel doubled. Conclusions: We hope that this work will motivate and facilitate investigators to use MESA data to investigate issues concerning TIA and stroke and will inform investigators seeking to adjudicate TIA and stroke in other studies

Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: The cardiovascular health study

10.1093/aje/kwj350American Journal of Epidemiology165178-8

Supplementary Material for: Adjudication of Transient Ischemic Attack and Stroke in the Multi-Ethnic Study of Atherosclerosis

<b><i>Background:</i></b> To describe adjudication of transient ischemic attack (TIA) and stroke in an observational study. <b><i>Methods:</i></b> We detail the process used to adjudicate TIA and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA), a large longitudinal cohort study. Two of three vascular neurologists adjudicated each event using specific protocols. We examined the initial agreement, effect of imaging on diagnosis of TIA versus ischemic stroke, and effect of strict and less strict criteria on the number of ischemic stroke subtypes classified as undetermined. <b><i>Results:</i></b> Of 573 adjudicated events over 13.5 years of follow-up, 95 (16.5%) had TIA and 269 (47.0%) had stroke: 211 (78.4%) ischemic, 43 (16.0%) hemorrhagic, and 15 (5.6%) other. Disagreements occurred on 16% of initial adjudication of events. Using results from imaging, the number with TIA decreased by 8.6% and with ischemic stroke increased by 4.1%. Using less strict criteria to classify ischemic stroke subtypes reduced the number classified as undetermined, from 137 to 59, and numbers classified as cardioembolic and small vessel doubled. <b><i>Conclusions:</i></b> We hope that this work will motivate and facilitate investigators to use MESA data to investigate issues concerning TIA and stroke and will inform investigators seeking to adjudicate TIA and stroke in other studies