Parco Chan

Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease

Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimers disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.

The effect of white matter hyperintensities on verbal memory: Mediation by temporal lobe atrophy

Objective To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias. Methods We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning. Results In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle −1.53, 95% bootstrap confidence interval [CI] −2.45 to −0.88; and confirmation −0.66, 95% CI [−0.95 to −0.41] words). This pathway was significant in subgroups with (−0.20, 95% CI [−0.38 to −0.07] words, n = 363) and without (−0.71, 95% CI [−1.12 to −0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (−1.82%, 95% CI [−2.64% to −1.11%]), a sensitive and specific sign of AD. Conclusions Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy.

Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report

White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimers disease (AD), but their interrelationships remain unclear.

Novel Phospholipid Signature of Depressive Symptoms in Patients With Coronary Artery Disease

Background Depression in patients with coronary artery disease (CAD) is associated with increased cardiovascular morbidity. Given the proinflammatory actions of phospholipids, aberrant phospholipid metabolism may be an etiological mechanism linking CAD and depression. Our primary objective was to identify a phospholipid biomarker panel that characterizes CAD patients with significant depressive symptoms from those without. Methods and Results We performed a targeted lipidomic analysis on CAD patients with significant depressive symptoms (n=37, Center for Epidemiologic Studies Depression score ≥16) and those without (n=49). Phospholipid species were selected using partial least‐square discriminant analysis, and the ability of the resulting model to discriminate between groups was evaluated using receiver operator characteristic curves. Biosignature scores were calculated from this model, and analyses of covariance were performed to compare intergroup differences in biosignature scores, with adjustment for clinical differences between patients. Those with significant depressive symptoms had lower cardiopulmonary fitness, more prevalent history of depression, and a greater number of vascular risk factors. A model of 10 phospholipid species had an area under the curve value of 0.84 (95% confidence interval 0.72‐0.95), sensitivity of 0.73, and specificity of 0.71. This model passed permutation testing (n=1000, P<0.001). Biosignature scores were higher in those with significant depressive symptoms after adjustment for potential confounders (F[1.86]=14.39, P<0.0005). Conclusions The present findings support the role of proinflammatory phospholipid species in the presence of depression in CAD patients from the CAROTID trial (Coronary Artery Disease Randomized Omega‐3 Trial in Depression). Future investigations should aim to replicate findings in larger data sets and clarify possible pathophysiological mechanisms. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00981383.

Longitudinal associations between 4-hydroxynonenal and depression in coronary artery disease patients

Depressive symptoms in patients with coronary artery disease (CAD) attenuate the cardiovascular benefits of cardiac rehabilitation (CR). Given that oxidative stress may be an important mechanism underlying depression, this study aimed to understand the longitudinal relationship between lipid peroxidation markers and depression in CAD. Serum levels of early (lipid hydroperoxides, LPH) and late (4‑hydroxy‑2-nonenal, 4-HNE; 8-isoprotane, 8-ISO) lipid peroxidation markers were measured in 120 CAD patients undergoing CR. The Structured Clinical Interview for DSM Axis I Disorders - Depression Module (SCID) was used to diagnose depression at baseline and the Center for Epidemiological Studies Depression Scale (CES-D) was used to measure depressive symptom severity. Multivariate mixed models compared the trajectories of serum LPH, 4-HNE, and 8-ISO between depressed and non-depressed CAD patients undergoing 6 months of CR. Similar models evaluated the associations between serum LPH, 4-HNE, and 8-ISO and CES-D score over the course of CR. Serum 4-HNE decreased less in CAD patients with depression compared to those without. In addition, a decrease in 4-HNE concentrations was significantly associated with a decrease in CES-D scores over 6 months. These findings suggest that 4-HNE may be an important marker of depressive symptoms in CAD and may be involved in its progression.

Palivizumab prophylaxis for respiratory syncytial virus in infants with cystic fibrosis: is there a need?

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study’s objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged <u20092xa0years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ2 and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B)u2009=u20090.23 [0.11–0.49], pu2009<u20090.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; tu2009=u20092.39 [dfu2009=u20097], pu2009=u20090.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (tu2009=u20093.52 [dfu2009=u200915], pu2009=u20090.003) and hospital LOS (tu2009=u20092.11 [dfu2009=u200952], pu2009=u20090.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups.