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To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p0.01) and low CSF-Aβ (p0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p0.05). In a similar logistic regression model, parietal and occipital (p0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p0.05) and occipital PVWMH and elevated CSF-phospho-tau (p0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18 fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUV max ) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUV ROImax ); (3) averaged mean SUV across 10 ROIs (SUV mean ). Results: Sixty-one patients were included. Plaque inflammatory FDG SUV max was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol ( p = 0.009), and triglycerides ( p = 0.01), and with lower high-density lipoprotein (HDL) ( p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUV mean (Spearman rho 0.44, p = 0.009), SUV ROImax (rho 0.33, p = 0.01), and SUV max (rho 0.35, p = 0.06). Total cholesterol was associated with SUV mean (rho 0.33, p = 0.009), with trends for SUV max (rho 0.24, p = 0.059) and SUV ROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUV max (rho 0.32, p = 0.01) and SUV ROImax (rho 0.35, p = 0.005). HDL was associated with lower SUV max (rho −0.37, p = 0.004) and SUV ROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL ( p = 0.008) and total cholesterol ( p = 0.04) were independently associated with SUV max . Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.

Objective: In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. Methods: In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. Results: Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset ( p = 0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients ( p = 0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days ( p = 0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6–837.5, p = 0.03), and 7 days (HR 9.1, 1.1–79.2, p = 0.05), with a trend at 14 days (HR 4.6, 0.9–22.8, p = 0.06). Conclusions: Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.