Comparative Analysis of Different Definitions of Amyloid-ß Positivity to Detect Early Downstream Pathophysiological Alterations in Preclinical Alzheimer.

Amyloid-ß (Aß) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early Aß pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer's continuum is critical. Here, we compare different Aß classification approaches and we show their performance in detecting pathophysiological changes downstream Aß pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer's continuum. Participants underwent Aß PET and CSF biomarkers assessment. We classified participants as Aß -positive using five approaches: (1) CSF Aß42 < 1098 pg/ml; (2) CSF Aß42/40 < 0.071; (3) Aß PET Centiloid > 12; (4) Aß PET Centiloid > 30 or (5) Aß PET Positive visual read. We assessed the correlations between Aß biomarkers and compared the prevalence of Aß positivity. We determined which approach significantly detected associations between Aß pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher Aß-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF Aß-positive but PET Aß-negative than CSF Aß-negative but PET Aß-positive. The CSF Aß 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the Aß-positive group. Altogether, we highlight the need for sensitive Aß -classifications to study the preclinical Alzheimer's continuum. Approaches that define Aß positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.

Plaque neovascularization detected with contrast-enhanced ultrasound predicts ischaemic stroke recurrence in patients with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast-enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels in vivo. Our aim was to determine if CEUS-detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow-up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence. RESULTS: We included 78 patients whose mean age was 74.3 ± 10.4 years. There were 29 (37.2%) patients with a low-grade stenosis (<50%). The remainder presented moderate (50%-69%) or high-grade (≥70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow-up of 14.1 (interquartile range, 9.5-19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS-detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66-26.01). CONCLUSION: In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.

The impact of exercise duration and intensity on the release of cardiac biomarkers.

Numerous studies have observed cardiac biomarker release with prolonged exercise. Despite this, we are unsure as to the constituent aspects of any given exercise bout that may be important in promoting cardiac biomarker release. This study examined the influence of exercise duration and intensity on the appearance of cardiac biomarkers. Twenty-one subjects ran for 45, 90 and 180 min at 85% and 95% of their individual anaerobic threshold on six different days randomized. Cardiac troponin I (cTnI) and N-terminal pro-brain natiuretic peptide (NT-proBNP) were assayed from blood samples collected before, 30 min and 3 h post-exercise. NT-proBNP was elevated after all exercise trials (range before: 21-32; range post: 38-67 ng/L). Peak post-exercise concentrations of NT-proBNP were associated with exercise duration (P=0.049), but not exercise intensity (P=0.451). cTnI was elevated after all exercise trials (range before: 0.007-0.011; range post: 0.008-0.021 µg/L). Peak post-exercise concentrations of cTnI were associated with exercise duration (P=0.003) and intensity (P=0.037). Data suggest that while both cTnI and NT-proBNP increased after all exercise trials, the mediating effect of duration influenced both NT-proBNP and cTnI while intensity influenced only cTnI.