Cardiac and Carotid Markers Link With Accelerated Brain Atrophy

OBJECTIVE: Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. APPROACH AND RESULTS: In the longitudinal population-based AGES–Reykjavik Study, we included 2430 subjects (mean age 74.6, 41.4% male) with baseline data on NT-proBNP and CITM (assessed by Ultrasound imaging). Participants underwent a high-resolution brain MRI at baseline and five years later to assess total brain (TBV), grey matter (GMV) and white matter (WMV) volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 ml (95% CI: −6.0, −1.1) decline in TBV and 3.5 ml (95% CI: −5.7, −1.3) decline in GMV. Likewise, each millimeter higher CIMT was associated with 10.8 ml (95% CI: −17.3, −4.2) decline in TBV and 8.6 ml (95% CI: −14.4, −2.8) decline in GMV. There was no association between NT-proBNP and CIMT and changes in WMV. Compared to participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 ml (95% CI: −6.0, −1.6) greater decline in their TBV and 4ml (95% CI: −6.0, −2.0) greater decline in GMW. These associations were independent of socio-demographic and cardiovascular factors. CONCLUSIONS: Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy

High blood pressure and resilience to physical and cognitive decline in the oldest old: The leiden 85-plus study

Objectives To evaluate the association between various blood pressure (BP) measures at age 85 and future decline in physical and cognitive function the oldest old. Design Longitudinal study. Setting The population-based Leiden 85-plus Study. Participants Five hundred seventy-two 85-year-old community-dwelling individuals. Measurements BP was measured at age 85 during home visits. Activities of daily living (ADLs) and Mini-Mental State Examination (MMSE) were assessed at age 85 and annually thereafter up to age 90. On average, participants were followed for 3.2 years. Cross-sectional and longitudinal analyses were performed using linear regression models using systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) as the determinants. All analyses were adjusted for sociodemographic and cardiovascular factors. Results At age 85, higher SBP and PP were associated with lower ADL disability scores (both P =.01). Similarly, higher SBP, DBP, and MAP were associated with higher MMSE scores (all P <.05). From age 85 onward, higher SBP (P <.001), MAP (P =.01), and PP (P =.003) at age 85 were associated with lower annual increases in ADL disability scores. Likewise, higher SBP (P =.03) and PP (P =.008) at age 85 were associated with lower annual declines in MMSE scores. Additional analyses showed that the association between high BP and lower annual decline in MMSE score was most pronounced in participants with high ADL disability. Conclusion In the oldest old, higher SBP and PP are associated with resilience to physical and cognitive decline, especially in individuals with pre-existing physical disability

Association of circulating metabolites in plasma or serum and risk of stroke:meta-analysis from seven prospective cohorts

Abstract Objective: To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings. Methods: We investigated the association of metabolites with risk of stroke in 7 prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by nuclear magnetic resonance technology. The relationship between metabolites and stroke was assessed with Cox proportional hazards regression models. The analyses were performed considering all incident stroke events and ischemic and hemorrhagic events separately. Results: The analyses revealed 10 significant metabolite associations. Amino acid histidine (hazard ratio [HR] per SD 0.90, 95% confidence interval [CI] 0.85, 0.94; p = 4.45 × 10−5), glycolysis-related metabolite pyruvate (HR per SD 1.09, 95% CI 1.04, 1.14; p = 7.45 × 10−4), acute-phase reaction marker glycoprotein acetyls (HR per SD 1.09, 95% CI 1.03, 1.15; p = 1.27 × 10−3), cholesterol in high-density lipoprotein (HDL) 2, and several other lipoprotein particles were associated with risk of stroke. When focused on incident ischemic stroke, a significant association was observed with phenylalanine (HR per SD 1.12, 95% CI 1.05, 1.19; p = 4.13 × 10−4) and total and free cholesterol in large HDL particles. Conclusions: We found association of amino acids, glycolysis-related metabolites, acute-phase reaction markers, and several lipoprotein subfractions with the risk of stroke. These findings support the potential of metabolomics to provide new insights into the metabolic changes preceding stroke