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Toward neuroimaging-based network biomarkers for transient ischemic attack.

ABSTRACT: Stroke is associated with topological disruptions of large-scale functional brain networks. However, whether these disruptions occur in transient ischemic attack (TIA), an important risk factor for stroke, remains largely unknown. Combining multimodal MRI techniques, we systematically examined TIA-related topological alterations of functional brain networks, and tested their reproducibility, structural, and metabolic substrates, associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers. We found that functional networks in patients with TIA exhibited decreased whole-brain network efficiency, reduced nodal centralities in the bilateral insula and basal ganglia, and impaired connectivity of inter-hemispheric communication. These alterations remained largely unchanged when using different brain parcellation schemes or correcting for micro head motion or for regional gray matter volume, cerebral blood flow or hemodynamic lag of BOLD signals in the patients. Moreover, some alterations correlated with the levels of high-density lipoprotein cholesterol (an index related to ischemic attacks via modulation of atherosclerosis) in the patients, distinguished the patients from healthy individuals, and predicted future ischemic attacks in the patients. Collectively, these findings highlight the emergence of characteristic network dysfunctions in TIA, which may aid in elucidating pathological mechanisms and establishing diagnostic and prognostic biomarkers for the disease.

SUBMITTER: Lv Y

PROVIDER: S-EPMC6865696 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Toward neuroimaging-based network biomarkers for transient ischemic attack.

Lv Yating Y Han Xiujie X Song Yulin Y Han Yu Y Zhou Chengshu C Zhou Dan D Zhang Fuding F Xue Qiming Q Liu Jinling J Zhao Lijuan L Zhang Cairong C Li Lingyu L Wang Jinhui J

Human brain mapping 20190419 11

Stroke is associated with topological disruptions of large-scale functional brain networks. However, whether these disruptions occur in transient ischemic attack (TIA), an important risk factor for stroke, remains largely unknown. Combining multimodal MRI techniques, we systematically examined TIA-related topological alterations of functional brain networks, and tested their reproducibility, structural, and metabolic substrates, associations with clinical risk factors and abilities as diagnostic ...[more]

PMID: 31004388

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Project description:Background and purposePremature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events.MethodsFifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement.ResultsDuring 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer.ConclusionsSeveral biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies.

Project description:Background and purposeDifferences in sex in the incidence, presentation, and outcome of events after ischemic stroke have been studied in depth. In contrast, only limited data are available after transient ischemic attack (TIA). We aim to assess sex-related differences in the presentation, cause, neuroimaging features, and predictors of long-term prognosis in patients with TIA.MethodsWe carried out a prospective cohort study of consecutive patients with TIA from January 2006 to June 2010. Nondefinitive TIA events were defined by the presence of isolated atypical symptoms. The risk of stroke recurrence (SR) and composite of major vascular events were stratified by sex after a median follow-up time of 6.5 (interquartile range, 5.0-9.6) years.ResultsAmong the 723 patients studied, 302 (41.8%) were female and 79 (10.9%) suffered a nondefinitive TIA event. Vascular territory diffusion-weighted imaging patterns (odds ratio, 1.61 [95% CI, 0.94-2.77]), and nondefinitive TIA events (odds ratio, 2.66 [95% CI, 1.55-4.59]) were associated with women, whereas active smoking (odds ratio, 0.30 [95% CI, 0.15-0.58]) and large artery atherosclerosis causes (odds ratio, 0.50 [95% CI, 0.29-0.83]) were related to men. The risk of SR was similar in both sexes (12.6% [95% CI, 8.9-16.3] for women versus 14.3% [95% CI, 11.0-17.6] for men). In contrast, the risk of major vascular events was significantly lower in women than in men (17.5% [95% CI, 13.2-21.8] versus 23.8% [95% CI, 19.7-27.9]). In both sexes, after adjusting for age, large artery atherosclerosis was associated with SR (hazard ratio, 3.22 [95% CI, 1.42-7.24] and hazard ratio, 2.00 [95% CI, 1.14-3.51]). In a Kaplan-Meier analysis, females with positive diffusion-weighted imaging (P=0.014) and definitive TIA (log-rank test P=0.022) had a significantly higher risk of SR.ConclusionsDespite similar risks of SR, there were sex-related differences in baseline characteristics, presenting symptoms, patterns of acute ischemic lesions, cause, and outcomes. These findings encourage further research into optimal preventive strategies that take into account these differences.

Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

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Toward neuroimaging-based network biomarkers for transient ischemic attack.

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Toward neuroimaging-based network biomarkers for transient ischemic attack.

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