Presence Of Silent Brain Infarction Research Articles

MRI Investigation of the Association of Left Atrial and Left Atrial Appendage Hemodynamics with Silent Brain Infarction.

Left atrial (LA) myopathy is thought to be associated with silent brain infarctions (SBI) through changes in blood flow hemodynamics leading to thrombogenesis. 4D-flow MRI enables in-vivo hemodynamic quantification in the left atrium (LA) and LA appendage (LAA). To determine whether LA and LAA hemodynamic and volumetric parameters are associated with SBI. Prospective observational study. A single-site cohort of 125 Participants of the multiethnic study of atherosclerosis (MESA), mean age: 72.3 ± 7.2 years, 56 men. 1.5T. Cardiac MRI: Cine balanced steady state free precession (bSSFP) and 4D-flow sequences. Brain MRI: T1- and T2-weighted SE and FLAIR. Presence of SBI was determined from brain MRI by neuroradiologists according to routine diagnostic criteria in all participants without a history of stroke based on the MESA database. Minimum and maximum LA volumes and ejection fraction were calculated from bSSFP data. Blood stasis (% of voxels <10 cm/sec) and peak velocity (cm/sec) in the LA and LAA were assessed by a radiologist using an established 4D-flow workflow. Student's t test, Mann-Whitney U test, one-way ANOVA, chi-square test. Multivariable stepwise logistic regression with automatic forward and backward selection. Significance level P < 0.05. 26 (20.8%) had at least one SBI. After Bonferroni correction, participants with SBI were significantly older and had significantly lower peak velocities in the LAA. In multivariable analyses, age (per 10-years) (odds ratio (OR) = 1.99 (95% confidence interval (CI): 1.30-3.04)) and LAA peak velocity (per cm/sec) (OR = 0.87 (95% CI: 0.81-0.93)) were significantly associated with SBI. Older age and lower LAA peak velocity were associated with SBI in multivariable analyses whereas volumetric-based measures from cardiac MRI or cardiovascular risk factors were not. Cardiac 4D-flow MRI showed potential to serve as a novel imaging marker for SBI. 3 TECHNICAL EFFICACY: Stage 2.

Association of Body Shape Index with Cerebral Small Vessel Disease

Introduction: A body shape index (ABSI) is an anthropometric index designed to reflect the influence of visceral fat. ABSI has been previously associated with various atherosclerosis, metabolic diseases, and cardiovascular diseases; however, relatively few studies have been conducted on cerebrovascular disease. In this study, we evaluated the association between ABSI and cerebral small vessel disease (cSVD) in health check-up participants. Methods: We evaluated consecutive health check-up participants between January 2006 and December 2013. As subtypes of cSVD, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of silent brain infarct (SBI) and cerebral microbleed (CMB). ABSI was calculated according to the following formula: ABSI (m^11/6/kg^−2/3) = waist circumference (m)/(body mass index [kg/m²]^2/3 × height [m]^1/2). Results: A total of 3,219 health check-up participants were assessed (median age, 56 years; male sex, 54.0%). In the multivariable analysis, ABSI was significantly associated with WMH volume (β = 0.107, 95% confidence interval [CI] = 0.013–0.200), SBI (adjusted odds ratio [aOR] = 1.62, 95% CI = 1.14–2.31), and CMB (aOR = 1.64, 95% CI = 1.16–2.33) after adjusting for confounders (per 100 m^11/6/kg^−2/3). Furthermore, ABSI showed a dose-response relationship with the burden of each cSVD pathology. Conclusions: High ABSI was associated with a higher burden of cSVD in health check-up participants. As ABSI showed close associations with all subtypes of cSVD, visceral fat may be a common risk factor penetrating cSVD pathologies.

Risk Factors for Silent Brain Infarcts and White Matter Disease in a Real-World Cohort Identified by Natural Language Processing

ObjectiveTo assess the frequency of silent brain infarcts (SBIs) and white matter disease (WMD) and associations with stroke risk factors (RFs) in a real-world population. Patients and MethodsThis was an observational study of patients 50 years or older in the Kaiser Permanente Southern California health system from January 1, 2009, through June 30, 2019, with head computed tomography or magnetic resonance imaging for nonstroke indications and no history of stroke, transient ischemic attack, or dementia. A natural language processing (NLP) algorithm was applied to the electronic health record to identify individuals with reported SBIs or WMD. Multivariable Poisson regression estimated risk ratios of demographic characteristics, RFs, and scan modality on the presence of SBIs or WMD. ResultsAmong 262,875 individuals, the NLP identified 13,154 (5.0%) with SBIs and 78,330 (29.8%) with WMD. Stroke RFs were highly prevalent. Advanced age was strongly associated with increased risk of SBIs (adjusted relative risks [aRRs], 1.90, 3.23, and 4.72 for those aged in their 60s, 70s, and ≥80s compared with those in their 50s) and increased risk of WMD (aRRs, 1.79, 3.02, and 4.53 for those aged in their 60s, 70s, and ≥80s compared with those in their 50s). Magnetic resonance imaging was associated with a reduced risk of SBIs (aRR, 0.87; 95% CI, 0.83 to 0.91) and an increased risk of WMD (aRR, 2.86; 95% CI, 2.83 to 2.90). Stroke RFs had modest associations with increased risk of SBIs or WMD. ConclusionAn NLP algorithm can identify a large cohort of patients with incidentally discovered SBIs and WMD. Advanced age is strongly associated with incidentally discovered SBIs and WMD.

Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation.

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients.Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography.Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03–2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) −0.47 (−0.84; −0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017).Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment.Clinical Trials Gov Identifier: NCT02105844.

Abstract P57: Risk Factors for Incidentally Discovered Silent Brain Infarcts and White Matter Disease in a Real World Cohort Identified by Artificial Intelligence

Introduction: Silent brain infarcts (SBIs) and white matter disease (WMD) are highly prevalent and associated with increased risk of ischemic stroke in patients with traditional stroke risk factors (RFs) in prospective cohort studies. Their frequency and associations with stroke RFs have not been well described in real world populations. Methods: This was a cross-sectional study of patients age ≥ 50 in the Kaiser Permanente-Southern California (KPSC) health system between 2009-2019 with a head CT or MRI for non-stroke indications and no history of ischemic stroke, transient ischemic attack, or dementia. A natural language processing (NLP) algorithm developed at Mayo Clinic and Tufts Medical Center was applied to the KPSC EHR to identify individuals with reported SBIs or WMD. Multivariable Poisson regression with robust error variance was used to estimate risk ratios of demographics, stroke RFs (from the Framingham Stroke Risk Score), and scan modality on the presence of SBIs or WMD. Results: Among 262,875 individuals, the NLP identified 13,154 (5.0%) with SBIs and 78,330 (29.8%) with WMD. Stroke RFs were highly prevalent in this cohort. The majority underwent CTs (74.8%) instead of MRIs as their initial neuroimaging. After adjustment for demographics and RFs, advanced age demonstrated a strong association with increased risk of SBIs and WMD (table). MRI was associated with a reduced risk of reported SBIs (ARR: 0.87, 95% CI 0.83-0.91) and an increased risk of reported WMD (ARR 2.86, 95% CI 2.83-2.90). Despite being prevalent, traditional stroke RFs had weak associations with increased risk of SBIs or increased risk of WMD. Conclusions: Advanced age is strongly associated with incidentally discovered SBIs and WMD on neuroimaging studies obtained in routine care. The development of SBIs and WMD may not be fully attributable to traditional stroke RFs.

Abstract P604: Incidentally-Discovered Asymptomatic Ischemic Lesions Identified Using Natural Language Processing Are Strong Risk Markers for Future Ischemic Stroke

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown. Methods: In this retrospective cohort study, Kaiser Permanente-Southern California health plan enrollees aged ≥ 50 years old with a brain CT or MRI scan between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the index neuroimaging report. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The Table below summarizes the crude stroke incidence rates. The crude hazard ratio (HR) was 3.40 (95% CI 3.25-3.56) for SBI and 2.63 (95% CI 2.54-2.71) for WMD. In the multivariable model controlling for all major stroke risk factors, the effect of SBI was found to be stronger in younger versus older patients and for MRI- versus CT-discovered lesions. With MRI, the average adjusted HR over time was 2.95 (95% CI 2.53-3.44) for those &lt; age 65 and 2.15 (95% CI 1.91-2.41) for those ≥ age 65. With CT scan, the average adjusted HR over time was 2.48 (95%CI 2.19-2.81) for those &lt; age 65 and 1.81 (95% CI 1.71-1.91) for those ≥ age 65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69-1.82) and was not modified by age or imaging modality. The effect of SBI decreased gradually over time, while the effect of WMD remained constant. Conclusion: Incidentally-discovered SBI and WMD are common in patients ≥ age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. The findings may represent an opportunity for stroke prevention.

Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry

Few data exist concerning the rate of silent cerebral ischaemic events following endovascular treatment of the aortic arch. The objective of this work was to quantify these lesions using the STEP registry (NCT04489277). This multicentre retrospective cohort study included consecutive patients treated with an aortic endoprosthesis deployed in Ishimaru zone 0–3 and brain diffusion weighted magnetic resonance imaging (DW-MRI) within seven days following the procedure. DW-MRI was performed to identify the location and number of new silent brain infarctions (SBI). All endografts were carbon dioxide flushed prior to implantation. The study population included 91 patients (mean age, 69 years; men, 64%) from two academic centres treated between September 2018 and January 2020. The procedure was elective in 71 patients (78%). The treatment was performed for a dissection, degenerative aneurysm, or other aortic disease in 44 (49%), 34 (37%), and 13 (14%) patients, respectively. Endografts were deployed in zone 0, 1, 2 or 3 in 23 (25%), 10 (11%), 47 (52%), and 11 (12%) patients, respectively. Endografts were branched (25%), fenestrated (17%), or tubular (58%). At 30 days, there were no deaths or clinical strokes. On cerebral DW-MRI, a total of 245 SBI were identified in 45 patients (50%). Lesions were in the left hemisphere in 63% of the patients (153/245), predominantly in the middle territory (94/245). Deployment in zone 0–1 (p = .026), placement of a branched or fenestrated endograft (p = .038), a proximal endoprosthesis diameter ≥ 40 mm (p = .038), and an urgent procedure (p = .005) were significantly associated with the presence of SBI on univariable analysis, while urgent procedure was found to be an independent predictor on multivariable analysis (binary logistic regression) (p = .002). SBI following endovascular repair of the aortic arch is frequent, although there were no clinical strokes. Innovative strategies to reduce the risk of embolisation need to be developed.

Incidentally-Discovered Silent Cerebrovascular Disease Identified Using Natural Language Processing Are Strong Risk Markers for Future Ischemic Stroke

Background: White matter disease (WMD) and silent brain infarction (SBI) are known risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown. Methods: We included patients age ≥ 50 in the Kaiser Permanente Southern California (KPSC) health system scanned between 2009-2019 with a head CT or MRI and no prior history of ischemic stroke, transient ischemic attack, or dementia. We used natural language processing (NLP) to identify patients with SBI and WMD from the corresponding report of the index neuroimage. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors. Results: Among 262,875 individuals receiving neuroimaging, NLP identified 13,154 (5·0%) with SBI and 78,330 (29·8%) with WMD. The incidence rate of future stroke was 32·5 (95% CI 31·1, 33·9) per 1,000 patient-years for patients with SBI; 19·3 (95% CI 18·9, 19·8) for patients with WMD and 6.8 (95% CI 6·7, 7·0) for patients without silent cerebrovascular disease. The crude HR associated with SBI was 3.40 (95% CI 3·25 to 3·56); and for WMD was 2·63 (95% CI 2·54 to 2·71). Adjusted for major stroke risk factors, the effect of incidentally-discovered SBI was found to be stronger in younger compared to older patients and for MRI- compared to CT-discovered lesions. With MRI, the adjusted HR was 2·95 (95% CI 2·53 to 3·44) for those = age 65. The adjusted HR associated with a finding of WMD was 1·76 (95% CI 1·69 to 1·82) and was not modified by age or imaging modality. Conclusion: Incidentally-discovered SBI and WMD are common in patients > age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. These findings present an opportunity for stroke prevention. Funding Statement: This work was funded by a National Institutes of Health (NIH) grant (R01-NS102233). Declaration of Interests: None to declare. Ethics Approval Statement: The study protocol was approved by Tufts Medical Center’s and KPSC’s Institutional Review Board.

Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry

Few data exist concerning the rate of silent cerebral ischaemic events following endovascular treatment of the aortic arch. The objective of this work was to quantify these lesions using the STEP registry (NCT04489277). This multicentre retrospective cohort study included consecutive patients treated with an aortic endoprosthesis deployed in Ishimaru zone 0-3 and brain diffusion weighted magnetic resonance imaging (DW-MRI) within seven days following the procedure. DW-MRI was performed to identify the location and number of new silent brain infarctions (SBI). All endografts were carbon dioxide flushed prior to implantation. The study population included 91 patients (mean age, 69 years; men, 64%) from two academic centres treated between September 2018 and January 2020. The procedure was elective in 71 patients (78%). The treatment was performed for a dissection, degenerative aneurysm, or other aortic disease in 44 (49%), 34 (37%), and 13 (14%) patients, respectively. Endografts were deployed in zone 0, 1, 2 or 3 in 23 (25%), 10 (11%), 47 (52%), and 11 (12%) patients, respectively. Endografts were branched (25%), fenestrated (17%), or tubular (58%). At 30 days, there were no deaths or clinical strokes. On cerebral DW-MRI, a total of 245 SBI were identified in 45 patients (50%). Lesions were in the left hemisphere in 63% of the patients (153/245), predominantly in the middle territory (94/245). Deployment in zone 0-1 (p=.026), placement of a branched or fenestrated endograft (p=.038), a proximal endoprosthesis diameter≥40mm (p=.038), and an urgent procedure (p=.005) were significantly associated with the presence of SBI on univariable analysis, while urgent procedure was found to be an independent predictor on multivariable analysis (binary logistic regression) (p=.002). SBI following endovascular repair of the aortic arch is frequent, although there were no clinical strokes. Innovative strategies to reduce the risk of embolisation need to be developed.

Association between KCNQ2, TCF4 and RGS18 polymorphisms and silent brain infarction based on whole‑exome sequencing.

Silent brain infarction (SBI) is a cerebral infarction identified through brain imaging. In particular, studies have shown that the presence of SBI in elderly patients increases their risk of cognitive dysfunction, impairment and dementia. However, little research has been published on the relevance of SBI to these risks for the Korean population. The association between potassium voltage‑gated channel subfamilyQ member2 (KCNQ2), transcription factor4 (TCF4) and regulator of G‑protein signaling18 (RGS18) genotypes and SBI were investigated using whole‑exome sequencing and PCR restriction fragment length polymorphism (RFLP) analysis. The study population included 407patients with SBI (171males) and 401control subjects (172males). Genotyping was performed using PCR RFLP. Interestingly, TCF4 rs9957668T>C polymorphisms were associated with SBI prevalence [TTvs.CC: adjusted odds ratio(AOR), 1.815, 95% confidence intervals (CI), 1.202‑2.740; TT vs. TC+CC: AOR,1.492, 95%CI,1.066‑2.088; TT+TCvs.CC:AOR,1.454, 95%CI,1.045‑2.203]. The combination of KCNQ2 rs73146513A>G and TCF4 rs9957668T>C genotypes was associated with increasing SBI prevalence (AG/CC: AOR,3.719, 95%CI,1.766‑7.833; AA/CC: AOR,3.201, 95%CI,1.387‑7.387). The present study showed that TCF4 rs9957668T>C polymorphisms may be risk factors for SBI. Therefore, the TCF4 rs9957668T>C polymorphism may serve as a biomarker for increased risk of SBI in the Korean population.

Abstract TP204: Intima-Media Thickness in the Carotid Bifurcation, But Not Cardio-Ankle Vascular Index or Ankle-Brachial Index, is Related to Silent Brain Infarct on Magnetic Resonance Imaging in Healthy, Middle-Aged Japanese Individuals

Background: Carotid ultrasonography is currently the principal noninvasive tool for evaluating subclinical atherosclerosis and carotid artery disease. Increased carotid intima-media thickness (IMT) may precede the development of atherosclerotic plaques. Several studies have shown that increased IMT is associated with increased incidence of stroke. Silent brain infarct (SBI) has been proposed as a strong subclinical risk marker for future symptomatic stroke onset. However, the relationship between SBI and elevated IMT in healthy, middle-aged Japanese individuals has not been adequately examined. Methods: We examined 280 Japanese adults (92 women; mean age, 52.9 ± 5 years) with no history of cardiocerebrovascular disease. We assessed all participants’ periventricular hyperintensities, deep subcortical white matter hyperintensities, SBI on magnetic resonance imaging, cardio-ankle vascular index (CAVI)/ankle-brachial index (ABI), and various vascular risk factors. In addition, we measured intima-media thickness at the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA). Results: Participants were categorized into two groups according to the presence or absence of SBIs, and we then compared the clinical characteristics of the two groups. Age, hypertension, increased HbA1c level, and decreased estimated glomerular filtration rate were found to be significantly associated with the SBI group. The odds ratio (OR) of the maximum IMT at the CB for the presence of SBI was 4.016 (95% confidence interval [CI], 1.565-10.304), even after adjusting for potential confounding factors. In contrast, the ORs of maximum IMT at the ICA and CCA as well as CAVI and ABI were not significant. Participants with IMTs ≥2 mm at the CB had a higher probability of the presence of SBI (OR, 26.451; 95% CI, 2.404-291.00). Conclusion: The maximum IMT at the CB was significantly correlated with the presence of SBI on MRI, but ABI or CAVI did not show significant correlation. Thus, compared to CAVI or ABI, carotid ultrasonography appears to be a very useful tool for noninvasively detecting SBI. In particular, IMTs ≥2 mm at the CB on carotid ultrasonography may be practical for identifying SBIs among middle-aged Japanese individuals.

Abstract 135: Examining the Information Loss Between Neuroimages and Neuroimaging Reports for Detection of Silent Brain Infarcts and White Matter Disease Using Artificial Intelligence Technologies

Background: Real world studies of silent brain infarction (SBI) and white matter disease (WMD) are impeded by challenges in cohort identification. Natural language processing (NLP) from imaging reports may facilitate future studies. However, electronic health records can be heterogeneous and the process of interpreting neuroimages and generating reports can vary. Understanding knowledge representation and relationships between neuroimages and imaging reports is crucial for using NLP to facilitate disease management and cohort identification. Methods: A balanced sample of head neuroimages (CT, MRI) of patients &gt;50 years without clinical histories of symptomatic stroke, TIA, or dementia were obtained at Mayo Clinic and Tufts Medical Center. A team of 4 radiology residents performed report interpretation (RI) on 1000 reports according to a standardized protocol for the presence of SBIs, the presence of WMD, and WMD grade. A random subsample of 400 was doubly read for interrater reliability. For benchmarking, a team of 4 neuroradiologists directly reviewed and described findings on a subsample of 182 images, each doubly read. We assessed interrater reliability for direct review (DR) and RI, and agreement between these 2 information sources. An NLP algorithm was developed to review and extract findings from 1000 imaging reports. Results: For DR, interrater reliability was moderate for SBIs and WMD (k = 0.53, 95% CI 0.43-0.64 and k = 0.47, 95% CI 0.33-0.61) and good for WMD grade (Spearman 0.71, p&lt;0.001). For RI, interrater reliability for SBIs, WMD and WMD grade was good (k = 0.88, 95% CI 0.80-0.97; k = 0.98, 95% CI 0.97-1.00; and Spearman = 0.985, p&lt;0.001, respectively). Agreement between DR and RI was good for SBIs (k = 0.77, 95% CI 0.67-0.86) and WMD (k = 0.65, 95% CI 0.54-0.77). Spearman rank correlations comparing WMD grade interpretation DR to RI was 0.60 (p&lt;0.001). In identifying the presence of SBIs and WMDs, the accuracy of the NLP algorithm was 0.991 and 0.994, respectively. Conclusion: For the presence of SBI and WMD, and WMD grade, agreement between RI and DR was similar to agreement between 2 neuroradiologists directly reviewing neuroimages. It is highly feasible to use NLP to identify patients with SBIs and WMDs for clinical studies.

High triglyceride/HDL cholesterol ratio is associated with silent brain infarcts in a healthy population

BackgroundTriglycerides (TG)/high-density lipoprotein (HDL) cholesterol ratio is a marker of small/dense low-density lipoprotein particles, which are closely associated with various metabolic and vascular diseases. However, the role of TG/HDL cholesterol ratio in cerebrovascular diseases has not been well studied. In this study, we evaluated the relationship between TG/HDL cholesterol ratio and the presence of silent brain infarct (SBI) in a neurologically healthy population.MethodsWe retrospectively evaluated consecutive participants in health check-ups between January 2006 and December 2013. SBI was defined as an asymptomatic, well-defined lesion with a diameter of ≥3 mm on T1- or T2-weighted images. TG/HDL cholesterol ratio was calculated after dividing absolute TG levels by absolute HDL cholesterol levels.ResultsOf 3172 healthy participants, 263 (8.3%) had SBI lesions. In multivariate analysis, TG/HDL cholesterol ratio was independently associated with SBI (adjusted odds ratio [aOR] = 1.16, 95% confidence interval [CI] = 1.00 to 1.34, P = 0.047). This association was prominent in males (aOR = 1.23, 95% CI = 1.03 to 1.48, P = 0.021), but not in females. In the analyses of the relationships between lipid parameters and SBI lesion burden, TG/HDL cholesterol ratio was positively correlated, and total cholesterol/TG ratio was negatively correlated with SBI lesion burden, in dose-response manners (P for trend = 0.015 and 0.002, respectively).ConclusionsThe TG/HDL cholesterol ratio was positively associated with the prevalence of SBI in a neurologically healthy population.

Abstract MP39: Association of MIND Diet Adherence With Brain Volume, Silent Brain Infarcts and Brain Atrophy in the Framingham Heart Study

Objective: Adherence to the Mediterranean- DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs) or brain atrophy. Methods: We aimed to evaluate, cross-sectionally and longitudinally, whether consumption of a diet consist with the MIND diet was associated with larger brain volumes, fewer SBIs and fewer atrophy in the community-based Framinham Heart Study. We included 1,904 participants (mean age 69 (SD, 9)) who completed a brain MRI and a validated food frequency questionnaire (FFQ). The MIND diet consists of 10 healthy and five unhealthy components (range: 0-15). A cumulative MIND diet score was calculated by averaging across three FFQs (exams 5 (1991-1995), 6 (1995-1998), and 7 (1998-2001)). From the total study population, 86 % completed all three FFQs. Brain MRI was performed proximal to exam 7 and again after a mean of 7 years (SD, 1.1) (n=1,317). Total brain volume (TBV), hippocampal volume (HPV), white matter hyperintensity volume (WMHV), expressed as a percentage of total cranial volume, and presence of SBIs were assessed from MRI scans. We used multivariable linear (TBV, HPV and WMHV) and logistic (SBIs) regressions for the cross-sectional analyses, and we analyzed the annualized change of TBV and HPV as atrophy measures using multivariable linear regression. Results: In cross-sectional analyses, higher MIND diet scores were significantly associated with larger TBV (β±SE, +0.09±0.04; p=0.03) after adjustment for basic demographic factors, total daily energy intake, and APOE e4 allele status, but was not associated with HPV (+0.001±0.001; p=0.09), WMHV (-0.01±0.01; p=0.27), SBIs (OR (95%CI), +1.01, 0.92:1.10; p=0.61) or atrophy (TBV, -0.001±0.01; p=0.88; HPV, -0.0003±0.001; p=0.62). After additional adjustments for cardiovascular risk factors the association with TBV was attenuated (+0.05±0.04; p=0.17). Significant interactions were observed for HPV by APOE ε4 status and BMI in the basic model. After stratification by APOE ε4 status, higher MIND diet scores were significantly associated with higher HPV among APOE ε4 non-carriers (+0.002±0.001; p=0.01) but not carriers (n=412). After stratification by BMI, higher adherence to the MIND diet was associated with larger HPV among participants with a BMI above 25 (+0.002±0.001; p=0.01), but not among participants with a BMI below 25. Conclusions: Higher adherence to the MIND diet was not independently associated with brain volume measures, SBIs or brain atrophy in our community cohort as the associations appeared to be mediated by cardiovascular risk factors. In addition, we observed that adherence to the diet was associated with larger brain volume measures in sub groups. Replication is needed to confirm our findings.

Night-time systolic blood pressure and subclinical cerebrovascular disease: the Cardiovascular Abnormalities and Brain Lesions (CABL) study.

Although ambulatory blood pressure (BP) is a better predictor of cardiovascular outcomes than office BP, its association with subclinical cerebrovascular disease is not clarified. We investigated the associations of office and ambulatory BP values with subclinical cerebrovascular disease in a population based, predominantly elderly cohort without prior stroke. Eight hundred and twenty-eight participants underwent 24-h ambulatory BP monitoring (ABPM), 2D echocardiography and brain magnetic resonance imaging in the Cardiac Abnormalities and Brain Lesion (CABL) study. Daytime, night-time, and 24-h BPs, nocturnal dipping pattern, morning surge (MS), and 24-h variability were assessed. Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV). The association of BP measures with the presence of SBI and upper quartile of log-WMHV (log-WMHV4) was analysed. SBIs were detected in 111 patients (13.4%). Mean log-WMHV was -0.99 ± 0.94. In multivariable analysis, only night-time systolic BP (SBP) was significantly associated with SBI [odds ratio (OR) 1.15 per 10 mmHg, P = 0.042], independent of cardiovascular risk factors, and pertinent echocardiographic parameters. Although daytime, night-time, 24-h BPs, and non-dipping pattern were all significantly associated with log-WMHV4 (all P < 0.05), night-time SBP showed the strongest association (OR 1.21 per 10 mmHg, P = 0.003) and was the sole independent predictor when tested against the other BP parameters. Office BP measures, MS, and BP variability were not associated with subclinical cerebrovascular disease in adjusted analyses. Elevated night-time SBP is strongly associated with subclinical cerebrovascular disease. Night-time SBP by ABPM allows to identify individuals at higher risk of hypertensive brain injury.

Serum gamma-glutamyl transferase is associated with silent brain infarcts in a healthy population

Background and aimsAlthough there is substantial evidence that serum gamma-glutamyl transferase (GGT) is associated with cerebrovascular diseases, its role in silent brain infarcts (SBIs) has not been addressed. In this study, we evaluated the relationship between serum GGT and the presence of SBI in a neurologically healthy population. MethodsWe evaluated a consecutive series of healthy volunteers recruited between January 2006 and December 2013. We conducted broad examinations in the form of health check-ups, which included brain magnetic resonance imaging and laboratory examinations including assessment of GGT levels. SBI was defined as asymptomatic, well-defined lesions with a dimeter of ≥3 mm with the same signal characteristics as cerebrospinal fluid on T1- or T2-weighted images. ResultsA total of 3145 healthy subjects were assessed, and 260 SBI cases were identified. In multivariate analysis, the highest GGT tertile was independently associated with SBI [adjusted OR (aOR) = 1.48, 95% confidence interval (CI) = 1.02 to 2.15, p = 0.040] in a dose-response manner (p for trend = 0.037). Age and hypertension were also found to be significant factors for SBI. In a stratified analysis by sex, these positive associations of GGT levels with SBI became more prominent in the male group (aOR = 2.14, 95% CI = 1.15 to 4.00, p = 0.017), with a significantly increasing trend (p for trend = 0.028), while there was no association among female participants. ConclusionsIncreased serum GGT levels were found to be associated with higher SBI prevalence in a neurologically healthy population.

Association Between Heart Rate and Subclinical Cerebrovascular Disease in the Elderly.

Although increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke. The study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed. Presence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was -0.92±0.93 (median, -1.05; min, -5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03-1.61; P=0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct. In a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.

Kidney dysfunction and silent brain infarction in generally healthy adults

BackgroundThe association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. MethodsThe data from the screening health check-up program in the Seoul National University Hospital Health Promotion Center from January 1, 2009 to December 31, 2013 were used. A total of 2594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using T2-weighted and FLAIR images. Kidney dysfunction was defined as eGFR<60ml/min/1.73m2. To assess the effect of kidney dysfunction on the small perforating branches of cerebral vessels, subgroup analysis was performed using the presence of SLI as a dependent variable. ResultsThe mean age was 56.8±9.3years, and 1422 subjects (54.8%) were male. The mean eGFR level was 81.9±15.4ml/min/1.73m2. The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend<0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio=1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio=1.71 to 1.87 in all four models). ConclusionKidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors of stroke followed by SBI.

Abstract TP173: Kidney Dysfunction and Silent Brain Infarction in Generally Healthy Adults

Purpose: The association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. Methods: A total of 2,594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using gradient-recalled echo MRI. Kidney dysfunction was defined as eGFR &lt; 60 ml/min/1.73 m 2 . Results: The mean age was 56.8 ± 9.3 years, and 1,422 subjects (54.8%) were male. The mean eGFR level was 81.9 ± 15.4 ml/min/1.73 m 2 . The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend &lt; 0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio = 1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio = 1.71 to 1.87 in all four models). Conclusion: Kidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors ofstroke followed by SBI.

N-terminal pro-brain natriuretic peptide and subclinical brain small vessel disease.

To study the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with several brain MRI markers of brain vascular disease in a sample of participants free of stroke and dementia. NT-proBNP plasma level was determined by means of a sandwich immunoassay method in a cohort study comprising 278 hypertensive patients. The presence of silent brain infarcts, brain microbleeds, enlarged perivascular spaces, and white matter hyperintensity volumes was assessed by brain MRI. We performed univariate and multivariate analyses to determine whether NT-proBNP was independently associated with these imaging markers, individually or combined. Median age was 63 years, and 41.4% were women. NT-proBNP remained independently associated with silent brain infarcts (odds ratio [OR] per 1-SD increase in NT-proBNP 2.11, 95% confidence interval [CI] 1.44-3.10), brain microbleeds (OR 1.79, 95% CI 1.15-2.78), basal ganglia enlarged perivascular spaces (OR 1.55, 95% CI 1.12-2.15), and white matter hyperintensity volumes (β 1.60, 95% CI 0.47-2.74), even after controlling for vascular risk factors, cardiovascular risk, atrial fibrillation, previous heart disease, duration of hypertension, and preventive treatments. A score combining several imaging markers was also related to NT-proBNP levels (common OR per 1-SD increase 1.74, 95% CI 1.21-2.50). NT-proBNP is independently associated with silent cerebrovascular lesions and could be a surrogate marker of vascular brain damage in hypertension.