Coronary artery disease is linked with demyelination and iron deposition in white matter watershed areas

Learning new motor skills relies on neural plasticity within motor and limbic systems. This study uniquely combined diffusion tensor imaging and multiparametric mapping MRI to detail these neuroplasticity processes. We recruited 18 healthy male participants who underwent 960min of training on a computer-based motion game, while 14 were scanned without training. Diffusion tensor imaging, which quantifies tissue microstructure by measuring the capacity for, and directionality of, water diffusion, revealed mostly linear changes in white matter across the corticospinal-cerebellar-thalamo-hippocampal circuit. These changes related to performance and reflected different responses to upper- and lower-limb training in brain areas with known somatotopic representations. Conversely, quantitative MRI metrics, sensitive to myelination and iron content, demonstrated mostly quadratic changes in gray matter related to performance and reflecting somatotopic representations within the same brain areas. Furthermore, while myelin and iron-sensitive multiparametric mapping MRI was able to describe time lags between different cortical brain systems, diffusion tensor imaging detected time lags within the white matter of the motor systems. These findings suggest that motor skill learning involves distinct phases of white and gray matter plasticity across the sensorimotor network, with the unique combination of diffusion tensor imaging and multiparametric mapping MRI providing complementary insights into the underlying neuroplastic responses.

Aim . To assess the Wnt1 and Wnt3a proteins levels in patients with stable coronary artery disease (CAD) and different phenotypes of coronary artery lesions. Material and methods . A cross-sectional study included 72 patients with a verified diagnosis of stable CAD (aged 45-75 years) and 30 healthy individuals (control group) without cardiovascular risk factors. Based on coronary angiography or multispiral computed tomography, patients were divided into two groups. Group I — with non-obstructive coronary artery lesions (non-obCAD, n=30; including 11 men (37.5%); median age — 66.0 years [60.5; 71.5]; body mass index (BMI) 26.7 [25.5-30.2] kg/m²); Group II — with obstructive coronary artery lesions (obCAD, n=42; including 30 men (71.4%); median age — 64.0 years [57.0; 72.0]; BMI 27.4; [24.8; 29.8] kg/m²). The control group included 30 volunteers (10 men (33.3%); median age — 28.0 years [26.0; 37.0]; BMI 22.0; [20.9; 25.3] kg/m²). All patients underwent standard laboratory testing (complete blood count, biochemistry blood test, urinalysis) and instrumental diagnostics: electrocardiography (ECG), 24-hour Holter ECG monitoring, echocardiography, stress echocardiography and/or myocardial perfusion scintigraphy with a stress test. The levels of Wnt1 and Wnt3a proteins, endothelin-1, interleukins (IL-1β, IL-6), and C-reactive protein were determined by enzyme-linked immunosorbent assay. Results . The CAD patient groups were comparable in age and BMI but differed in sex: the obstructive CAD group was predominantly male (71.4%), while females predominated (62.5%) in the non-obstructive CAD group. The level of Wnt1 protein was significantly higher in the obstructive CAD group (0.19 ng/ml) compared to both the non-obstructive CAD (0.15 ng/ml; p<0.001) and control groups (0.15 ng/ml; p=0.001). The level of Wnt3a was also higher in the obstructive CAD group (0.24 ng/ml) and the control group (0.25 ng/ml) than in the non-obstructive CAD group (0.11 ng/ml; p<0.001). Endothelin-1 levels were higher in the nonobstructive CAD group (33.5 pg/ml) than in the obstructive CAD group (27.3 pg/ml; p=0.027). Inflammatory markers (IL-1β, IL-6, CRP) did not differ significantly. Factor analysis revealed two main components: “lipid profile” and “endothelial damage” (Wnt1, Wnt3a, and endothelin-1). ROC analysis showed the second component had high prognostic ability for differentiating CAD phenotypes (AUC=0.987; p<0.001). A logistic regression model based on Wnt1 and Wnt3a demonstrated high accuracy (AUC=0.953) in identifying obstructive CAD. Conclusion . The obtained data may suggest a possible role of the Wnt signaling pathway in the pathogenesis of different types of coronary artery lesions in CAD. Increased levels of Wnt1 and Wnt3a were associated with obstructive coronary artery lesions. An attempt was made to develop a regression model based on Wnt1 and Wnt3a concentrations. The resulting model has high diagnostic value for identifying patients with obCAD. This allows considering these proteins as potential prognostic biomarkers for risk stratification and clarifying the type of coronary artery lesion in CAD.

In patients with uncomplicated diabetes, there is low probability of finding significant coronary artery disease (CAD) by noninvasive tests. Therefore, screening for its presence is not justified, and it is important to find reliable predictors of silent CAD to identify patients with uncomplicated diabetes for further screening. The relationship between lipoprotein(a) [Lp(a)], apolipoprotein(a) [apo(a)] polymorphism, and silent CAD has never been studied. We investigated the association of Lp(a) and apo(a) polymorphism with angiographically documented asymptomatic CAD in type 2 diabetic patients without evident complications. A total of 1,323 diabetic patients without any clinical and electrocardiographic evidence of CAD were evaluated. Of 121 patients with highly positive results of exercise electrocardiography (ECG) (n = 30) or positive results on exercise thallium scintigraphy (n = 91), 103 subjects showed angiographically documented CAD (CAD group). Of 1,106 patients with negative results on exercise ECG, 103 subjects without CAD (NO CAD group) were selected and matched by age, gender, and duration of diabetes to patients in the CAD group. In patients in the NO CAD group, results of exercise ECG, 48-h ambulatory ECG, and stress echocardiography were negative for CAD. The CAD group had higher Lp(a) levels (21.7 +/- 17.7 vs. 15.2 +/- 19.0 mg/dl; P = 0.0093) than the NO CAD group, and a percentage of subjects had at least one small apo(a) isoform (68.9 vs. 29.1%; P = 0.0000) higher than the NO CAD group. Logistic regression analysis showed that apo(a) phenotypes (odds ratio [OR] 8.13, 95% CI 3.65-21.23), microalbuminuria (5.38, 2.44-11.88), smoking (2.72, 1.31-5.64), and Lp(a) levels (2.41, 1.15-5.03) were predictors of asymptomatic CAD. Our investigation reports the first evidence of an independent association of Lp(a) and apo(a) polymorphism with asymptomatic CAD. This suggests that Lp(a) levels and apo(a) phenotypes could be used together with other risk factors as markers of asymptomatic CAD in patients with diabetes.

The extracellular miRNAs circulate in the bloodstream and may serve as novel diagnostic and therapeutic biomarkers. The aim of the present study was to investigate circulating Toll-like receptor 4 (TLR4)-responsive miRNA expression in patients with coronary artery disease (CAD) and to examine the effects of renin-angiotensin system (RAS) blockade and statins on miRNA levels. This study included 41 patients with CAD and 20 subjects without CAD (non-CAD). Plasma TLR4-responsive miRNA samples were analysed using a microarray assay for 1700 human miRNA. The candidate miRNAs were verified with real-time reverse transcription (RT)-PCR. Patients with CAD were randomized to 12 months of combined treatment with either telmisartan and atorvastatin [angiotensin II receptor blocker (ARB)] or enalapril and atorvastatin [angiotensin-converting enzyme inhibitor (ACEI)]. Plasma samples were obtained from peripheral blood at baseline and after 12 months. The microarray assay showed significant differences in seven TLR4-responsive miRNAs between the CAD and non-CAD groups (P<0.05). Real-time PCR verified that miR-31, miR-181a, miR-16 and miR-145 were significantly lower in the CAD group than in the non-CAD group (P<0.01). Levels of TLR4 protein were higher in the CAD group than in the non-CAD group (P<0.01) and were negatively correlated with levels of TLR4-responsive miRNAs. Receiver operating characteristic (ROC) curve analysis revealed that a panel of these four miRNAs was sensitive and specific enough to distinguish CAD from non-CAD [area under the curve (AUC)=0.93, 95% CI (confidence interval)=0.99-0.87]. Both ARB and ACEI groups showed increased TLR4-responsive miRNAs and diminished levels of TLR4 protein (P<0.05). Changes in miRNAs and TLR4 levels were greater in the ARB group than in the ACEI group (P<0.05). Circulating TLR4-responsive miRNAs including miR-31, miR-181a, miR-16 and miR-145 were significantly lower in patients with CAD compared with controls and these miRNAs may be involved in the pathogenesis of CAD.

Matrix metalloproteinase (MMP)-3 and MMP-9 polymorphisms are characterized by plaque stability in coronary arteries. The aim of the current study was to investigate the 5A/6A polymorphism in the MMP-3 gene and C/T polymorphism in the MMP-9 gene in patients with coronary artery disease (CAD). The study population consisted of 400 patients who underwent coronary angiography. There were two groups consisting of 200 consecutive patients with CAD, presenting with stable angina pectoris, and 200 consecutive patients exhibiting normal coronary arteries. Two single nucleotide polymorphisms in the MMP gene, MMP-3 and MMP-9, were detected using a polymerase chain reaction-restriction fragment length polymorphism assay. Mean age, gender distribution, smoking status, presence of diabetes mellitus and hypercholesterolemia were identified to be similar between the groups. One hundred and twenty seven (63.5%) patients had hypertension in the CAD group, whereas only 55 (27.5%) patients had hypertension in the control group (P<0.001). No significant difference in frequency of alleles and genotypes of MMP-9 C→T between the CAD and control groups was identified. The 5A allele frequency of MMP-3 in the CAD group was significantly higher when compared with the control group (P<0.001; odds ratio=2.18). The genotype frequency of MMP-3 5A/5A in the CAD group was significantly higher when compared with the controls (P=0.005). When compared with the homozygous wild-type (6A/6A) genotype of the MMP-3 gene, the cumulative frequency of heterozygote and homozygote genotypes of the MMP-3 gene was significantly higher in the CAD compared with the control group (P<0.001). Thus, the present study demonstrated that the 5A/5A and 6A/5A+5A/5A genotypes of the MMP-3 gene were associated with an increased risk of CAD.

Coronary artery ectasia (CAE) and coronary artery stenotic disease (CASD) represent distinct pathologies of the coronary arteries with remarkable clinical and angiographic features. Objectives: The study aims to find the angiographic features of patients with coronary artery ectasia compared with stenotic coronary artery disease. Methods: This retrospective study was conducted at Prime Teaching Hospital Peshawar from April 2023 to March 2024. Data were collected from 185 patients. Patients with a history of coronary artery bypass grafting or coronary intervention were excluded from the study. Baseline demographic and clinical characteristics, including age, gender, cardiovascular risk factors, hypertension, diabetes mellitus, hyperlipidemia, smoking history and presenting symptoms, were collected from electronic medical records. Results: Data were collected from 185 patients. The mean age of patients in the CAE group was 58.5 ± 8.3 years, and the CAD group was 63.2 ± 7.9 years. 55.6% of the male group was in CAE and 87% in the CAD group. Out of 185, 33% suffered from hypertension in CAE and 81.4% in the CAD group. The most common comorbidity was hyperlipidemia in the CAD group (72.9%). Stable angina was present in 44.4% of CAE and 60.7% of the CAD group. Unstable angina is most common in the CAD group (21.4%), and AMI was 10.7% and 11.1% in the CAD and CAE groups, respectively. Percutaneous Coronary Intervention (PCI) was most common in the CAD group, which was 75%. Conclusion: It is concluded that coronary artery ectasia (CAE) presents distinct angiographic and clinical features compared to stenotic coronary artery disease (CAD), including localised or diffuse dilatation of coronary arteries, a higher prevalence of silent ischemia, and lower utilisation of percutaneous coronary intervention (PCI).

To evaluate, by using quantitative MRI metrics, subtle cortical changes in brains of patients with the adult form of myotonic dystrophy type I (DM1) who showed no or minimal abnormalities on MRI. DM1 is an autosomal dominant multisystem disorder caused by the expansion of CTG repeats in the myotonic dystrophy-protein kinase gene. Mild to severe involvement of the CNS can be part of the clinical features of the disease. Several MRI studies have demonstrated that both focal white matter (WM) lesions and diffuse grey matter atrophy can be found in the brains of DM1 patients. However, whether these two processes are related or may occur independently is not clear. Ten genetically-proven DM1 patients who showed no or minimal abnormalities on MRI underwent a new brain MRI examination to obtain computerized measures of total and regional brain volumes normalized to head size and regional measurements of the magnetization transfer ratio (MTr). Normalized brain volumes (NBV) were significantly (p < 0.0001) lower in DM1 subjects than in a group of age- and sex-matched normal controls. Normalized cortical volumes (NCV) also were lower (p = 0.003) in DM1 subjects than in normal controls, whereas normalized WM volumes were not different between the two groups (p = 0.3). In agreement with this, values of MTr in the neocortex (cortical-MTr) were significantly (p = 0.006) lower in DM1 patients than in normal controls and this difference was not found in the WM tissue (p = 0.8). Neocortical damage seems to be evident in the absence of visible WM lesions suggesting that a neocortical pathology, unrelated to WM lesion formation, occurs in DM1 brains.

Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability ascribed to the autism spectrum disorder. Studies with FXS patients have reported altered white matter volume compared to controls. The Fmr1 knockout (KO) mouse, a model for FXS, showed evidence of delayed myelination during postnatal brain development. In this study, we examined several white matter regions in the male Fmr1 KO mouse brain compared to male wild-type (WT) mice at postnatal days (PND) 18, 21, 30, and 60, which coincide with critical stages of myelination and postnatal brain development. White matter volume, T₂ relaxation time, and magnetization transfer ratio (MTR) were measured using magnetic resonance imaging and myelin content was determined with histological staining of myelin. Differences in the developmental accumulation of white matter and myelin between Fmr1 KO and WT mice were observed in the corpus callosum, external and internal capsules, cerebral peduncle, and fimbria. Alterations were more predominant in the external and internal capsules and fimbria of Fmr1 KO mice, where the MTR was lower at PND 18, then elevated at PND 30, and again lower at PND 60 compared to the corresponding regions in WT mice. The pattern of changes in MTR were similar to those observed in myelin staining and could be related to the altered protein synthesis that is a hallmark of FXS. While no significant changes in white matter volumes and T₂ relaxation time between the Fmr1 KO and WT mice were observed, the altered pattern of myelin staining and MTR, particularly in the external capsule, reflecting the abnormalities associated with myelin content is suggestive of a developmental delay in the white matter of Fmr1 KO mouse brain. These early differences in white matter during critical developmental stages may contribute to altered brain networks in the Fmr1 KO mice.

Hypothesis: The dense stroma present in pancreatic ductal adenocarcinoma (PDA) harbors a unique tumor microenvironment (TME) that is immune suppressive and underlies the chemo-resistance of PDA. We have evaluated synthetic vitamin D combined with chemoimmunotherapy in a pilot clinical study (NCT03519308). To elucidate the underlying mechanisms of this treatment, we designed a matched study in a genetically engineered mouse model of PDA (KPC mice) to test the hypothesis that synthetic vitamin D enhances the effect of chemotherapy with or without immune checkpoint inhibition. To detect changes in TME, we have integrated diffusion weighted (DW) and dynamic contrast enhanced (DCE) MRI with immunohistochemistry (IHC) and single cell RNA sequencing (scRNAseq). Methods: KPC mice were randomly assigned to one of four groups: 1) Control (untreated); 2) Nab-paclitaxel + gemcitabine + cisplatin (Chemo); 3) Chemo + synthetic vitamin D (calcipotriol, Cal); 4) Chemo + Cal + PD-L1. The treatment lasted for 14 days followed by euthanasia and tumor collection for IHC and scRNAseq. Respiratory motion-robust DW- and DCE-MRI were performed on treatment days 0, 7 and 14. Results: Compared to consistent tumor growth (measured by MRI) in the Control group, both progression and regression were observed in groups 2) - 4), suggesting that the KPC model captured the varied treatment responses observed in the clinic. Capillary perfusion/permeability of the tumor measured by Ktrans (a DCE-MRI metric) was reduced at day 7 in the Chemo group (P&amp;lt;0.05), whereas Chemo+Cal reversed the reduction of Ktrans. Chemo-induced Ktrans reduction was corroborated with a significant reduction of microvascular density by IHC of CD31 compared to the Control. Addition of PD-L1 did not appear to enhance the tumor growth delay by Chemo+Cal. scRNAseq analysis revealed that while Chemo significantly delayed the tumor growth compared to the Control, it increased the portion of mesenchymal cells in the tumor and upregulated epithelial-to-mesenchymal transition (EMT) genes known to resist chemotherapy. In contrast, Chemo+Cal increased the fraction of epithelial cells and downregulated EMT genes compared to Chemo. Trasncriptome analysis of the tumor cells demonstrated that Chemo treatment increased the expression of Fibronectin 1 (FN1), a gene associated with tumor invasiveness, EMT, and metastasis, while lowering the expression of Trefoil Factor Family1 (Tff1), which is related to tumor-suppression and chemosensitivity. Chemo+Cal treatment reversed the expression of both FN1 and Tff1 gene compared to Chemo treatment. Conclusion: Single cell transcriptome analysis provided valuable insights into treatment-induced molecular subtype changes, which may predict future resistance and invasiveness. Our study revealed important mechanisms of calcipotriol that enhance the efficacy of chemotherapy by improving microvascular perfusion and permeability and by reducing chemo-resistance by enriching epithelial cells in PDA tumors. Citation Format: Hoon Choi, Mamta Gupta, Thomas Karasic, Miguel Joaquim, Emma Furth, Stephen Pickup, Cynthia Clendenin, Hee Kwon Song, Yong Fan, Jeffrey Duda, James Gee, Mark Rosen, Peter O’Dwyer, Rong Zhou. Quantitative MRI metrics and single cell transcriptome reveal effects of stroma-directed drug and chemotherapy in a GEM model of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A089.

Beyond Pathology: MRI-derived Metrics Unlock Preoperative Prognostic Risk Stratification in Breast Cancer.

Background: Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. Methods: To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 146 consecutive male patients with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. 28 male normoglycemic patients without CAD matched on age were served as control subjects. Results: The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the area under the curves (AUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0287; RLP-C, P = 0.0386). There were no significant differences in the AUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) x (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0311; IRI, P = 0.0235). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.4381, P &lt;0.0001; AUC-RLC-P, r = 0.3953, P &lt;0.0001), and they correlated well with the insulin resistance index (AUC-TG, r = 0.7194, P &lt;0.0001; AUC-RLC-P, r = 0.6621, P &lt;0.0001). Conclusions: We found that the insulin resistance showed a close relationship with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic state, may be a risk for postprandial impaired lipid metabolism.

Patients with coronary artery disease (CAD) face an increased risk of cognitive impairment, dementia, and stroke. While white matter (WM) lesions are frequently reported in patients with CAD, the effects on WM microstructure alterations remain largely unknown. We aimed to identify WM microstructural alterations in individuals with CAD compared with healthy controls (HC) and to examine their relationships with cognitive performance. Forty-three (43) patients with CAD (35 males and 8 females) and 36 HC (26 males and 10 females) aged 50 and older underwent comprehensive neuropsychological testing and multimodal 3 T magnetic resonance imaging (MRI). A novel multivariate approach-the Mahalanobis distance (D2)-was used to quantify WM abnormalities as the amount of deviation from the HC reference group. D2 integrates multiple MRI-derived diffusion-weighted imaging, R1 relaxometry, and magnetization transfer imaging metrics, while accounting for covariance between metrics. Relationships between WM D2 and cognition (executive function and processing speed) were also assessed. Compared with HCs, patients with CAD had higher D2 values in the whole WM (p = 0.015) and in the right anterior and bilateral middle cerebral artery territories (p < 0.05). Myelin-sensitive metrics, particularly R1 relaxation rate and MT saturation, were the most important contributors to D2. Processing speed was positively associated with greater R1 in both the whole WM and left middle cerebral artery territory. These findings suggest that greater WM microstructural alterations observed in patients with CAD were mainly driven by differences in myelin content. These alterations may contribute to a heightened risk of cognitive impairment.

We aimed to investigate the relationship between coronary artery disease (CAD) and systemic inflammation indices and lipid metabolism-related factors and subsequently, discuss the clinical application of these factors in CAD. We enrolled 284 consecutive inpatients with suspected CAD and divided them into a CAD group and a non-CAD group according to coronary angiography results. Serum levels of angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4), and tumor necrosis factor-α (TNF-α) levels were assessed using the ELISA and the systemic inflammation indices were calculated. Multivariate logistic regression was used to assess the risk factors of CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. The neutrophil-to-high density lipoprotein cholesterol ratio (5.04 vs. 3.47), neutrophil-to-lymphocyte ratio (3.25 vs. 2.45), monocyte-to-high density lipoprotein cholesterol ratio (MHR) (0.46 vs. 0.36), monocyte-to-lymphocyte ratio (0.31 vs. 0.26), systemic immune-inflammation index (SII) (696.00 vs. 544.82), serum TNF-α (398.15 ng/l vs. 350.65 ng/l), FABP4 (1644.00 ng/l vs. 1553.00 ng/l), ANGPTL3 (57.60 ng/ml vs. 52.85 ng/ml), and ANGPTL4 (37.35 ng/ml vs. 35.20 ng/ml) values showed a significant difference between the CAD and non-CAD groups ( P < 0.05). After adjusting for confounding factors, the following values were obtained: ANGPTL3 > 67.53 ng/ml [odds ratio (OR) = 8.108, 95% confidence interval (CI) (1.022-65.620)]; ANGPTL4 > 29.95 ng/ml [OR = 5.599, 95% CI (1.809-17.334)]; MHR > 0.47 [OR = 4.872, 95% CI (1.715-13.835)]; SII > 589.12 [OR = 5.131, 95% CI (1.995-13.200)]. These factors were found to be independently associated with CAD ( P < 0.05). Diabetes combined with MHR > 0.47, SII > 589.12, TNF-α >285.60 ng/l, ANGPTL3 > 67.53 ng/ml, and ANGPTL4 > 29.95 ng/l had the highest diagnostic value for CAD [area under the curve: 0.921, 95% CI, (0.881-0.960), Sensitivity: 88.9%, Specificity: 82.2%, P < 0.001]. MHR > 0.47, SII > 589.12, TNF-α >285.60 ng/l, ANGPTL3 > 67.53 ng/ml, and ANGPTL4 > 29.95 ng/l were identified as independent CAD risk factors and have valuable clinical implications in the diagnosis and treatment of CAD.

Objective: The aim of this study is to assess the association between epicardial adipose tissue (EAT) and coronary artery disease (CAD) via meta−analysis. Methods: Specific searches of online databases from January 2000 to May 2022 were conducted. All observational studies evaluating the association between EAT and CAD in PubMed, Web of Science, and the Cochrane Library databases were screened. A meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta−Analyses guidelines (PRISMA). In total, 21 studies encompassing 4975 subjects met the inclusion criteria, including 2377 diagnosed and assigned as the CAD group, while the other 2598 were assigned as the non−CAD group. Subjects in the CAD group were further divided into the severe stenosis group (stenosis ≥ 50%, n = 846) and the mild/moderate stenosis group (stenosis < 50%, n = 577). Results: Both the volume and thickness of EAT in the CAD group were larger compared to the non−CAD group (p < 0.00001). In a subgroup analysis within the CAD group, the severe stenosis group had a larger volume and thickness with respect to EAT when compared to the mild/moderate group (p < 0.001). Conclusions: The enlargement of EAT presented in CAD patients with an association with CAD severity. Although limited by different CAD types and measuring methods for EAT, as well as a smaller sample size, our results suggest that EAT is a novel predictor and a potential therapeutic target for CAD.

BackgroundCSF Ab42 levels are associated with myelin content alterations in cognitively‐unimpaired adults (Dean et al, 2017), suggesting that myelin alterations may be an early feature of the Alzheimer’s disease (AD) pathophysiological cascade. We expand on these prior findings to examine longitudinal change in myelin content.Method98 cognitively‐unimpaired (Table 1) participants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent longitudinal multicomponent relaxometry (mcDESPOT) MRI, T2FLAIR MRI, and lumbar puncture (LP). All mcDESPOT MRI were normalized to MNI space using ANTs. White matter lesion volumes were extracted from T2FLAIR images using Lesion Segmentation Toolbox version 2.0.1 in SPM12. CSF was assayed for Ab42 using enzyme‐linked immunosorbent (INNOTEST) methods. 212 mcDESPOT‐derived myelin water fraction (MWF) maps, sensitive to myelin content, were generated for this analysis. MWF values were extracted from 6 white matter tracts affected in AD, and MWF values were averaged across regions to create a global index of myelin content at each timepoint. Linear mixed models were fit with longitudinal regional or global MWF as the outcome. All models included random intercepts and age‐related slopes with fixed effects of age (mean‐centered), sex, years between MRI and LP, white matter hyperintensity volume (log‐transformed) measured at first MRI, CSF Ab42 (mean‐centered) levels measured near first MRI, and Age*Ab42. All models were fitted in R (“lmer” package) version 3.6.0 and considered significant at unadjusted p &lt; .05.ResultWe observed widespread age associations with myelin content such that older age associated with lower global myelin content (Figure 1) and lower CSF Ab42 was associated with lower global myelin content (Figure 2). There was no significant interaction of age and CSF Ab42 on global myelin content. However, an age*Ab42 effect in the cingulum and uncinate fasciculus indicated that older age and lower CSF Ab42 was associated with decreased myelin content (Figure 3).ConclusionWe previously found that lower CSF Ab42 was associated with lower myelin content among cognitively unimpaired adults. Here, we determined that for cognitively unimpaired middle‐aged adults, amyloid‐related longitudinal changes in myelin content also occur. Future studies will test if amyloid‐related myelin alterations may account for AD cognitive decline.