The relationship between white matter microstructure and self-perceived cognitive decline

Subjective cognitive decline (SCD) is a perceived cognitive change prior to objective cognitive deficits, and although it is associated with Alzheimer's disease (AD) pathology, it likely results from multiple underlying pathologies. We investigated the association of white matter microstructure to SCD as a sensitive and early marker of cognitive decline and quantified the contribution of white matter microstructure separate from amyloidosis. Vanderbilt Memory & Aging Project participants with diffusion MRI data and a 45-item measure of SCD were included [n = 236, 137 cognitively unimpaired (CU), 99 with mild cognitive impairment (MCI), 73 ± 7 years, 37% female]. A subset of participants (64 CU, 40 MCI) underwent a fasting lumbar puncture for quantification of cerebrospinal fluid (CSF) amyloid-β(CSF Aβ42), total tau (CSF t-tau), and phosphorylated tau (CSF p-tau). Diffusion MRI data was post-processed using the free-water (FW) elimination technique, which allowed quantification of extracellular (FW) and intracellular compartment (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) microstructure. Microstructural values were quantified within 11 cognitive-related white matter tracts, including medial temporal lobe, frontal transcallosal, and fronto-parietal tracts using a region of interest approach. General linear modeling related each tract to SCD scores adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile scores, APOE ε4 carrier status, diagnosis, Geriatric Depression Scale scores, hippocampal volume, and total white matter volume. Competitive models were analyzed to determine if white matter microstructural values have a unique role in SCD scores separate from CSF Aβ42. FW-corrected radial diffusivity (RDT) was related to SCD scores in 8 tracts: cingulum bundle, inferior longitudinal fasciculus, as well as inferior frontal gyrus (IFG) pars opercularis, IFG orbitalis, IFG pars triangularis, tapetum, medial frontal gyrus, and middle frontal gyrus transcallosal tracts. While CSF Aβ42 was related to SCD scores in our cohort (Radj2 = 39.03%; β = −0.231; p = 0.020), competitive models revealed that fornix and IFG pars triangularis transcallosal tract RDT contributed unique variance to SCD scores beyond CSF Aβ42 (Radj2 = 44.35% and Radj2 = 43.09%, respectively), with several other tract measures demonstrating nominal significance. All tracts which demonstrated nominal significance (in addition to covariates) were input into a backwards stepwise regression analysis. ILF RDT, fornix RDT, and UF FW were best associated with SCD scores (Radj2 = 46.69%; p = 6.37 × 10-12). Ultimately, we found that medial temporal lobe and frontal transcallosal tract microstructure is an important driver of SCD scores independent of early amyloid deposition. Our results highlight the potential importance of abnormal white matter diffusivity as an early contributor to cognitive decline. These results also highlight the value of incorporating multiple biomarkers to help disentangle the mechanistic heterogeneity of SCD as an early stage of cognitive decline

Saprochaete capitata fungal infection in renal transplant recipient

Saprochaete capitata is a fungus that rarely causes human infections; majority of infections were reported in patients with hematological malignancies. Here, we report a case of Saprochaete capitata infection in a renal transplant recipient. To the best of our knowledge, this is the first case report of infection with this unusual organism in renal transplant recipients. In our patient, this organism was isolated from broncho alveolar lavage, and it responded dramatically to the combination of amphotericin and voriconazole

A Blueberry-Enriched Diet Improves Renal Function and Reduces Oxidative Stress in Metabolic Syndrome Animals: Potential Mechanism of TLR4-MAPK Signaling Pathway

Metabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardio-renal diseases. Recent evidence indicates that antioxidants from berries are alternative to attenuate oxidative stress and inflammation. We tested the hypothesis that inflammation-induced renal damage is triggered by the activation of TLR4, and subsequent modulation of redox-sensitive molecules and mitogen-activated protein kinase (MAPK) pathway.Five-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry-enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance test and acute renal clearance experiments were performed. Gene and protein expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were measured. Kidney redox status and urinary albumin levels were quantified. Renal pathology was evaluated histologically.Control OZR exhibited lower glucose tolerance; exacerbated renal function parameters; increased oxidative stress. Gene and protein expression levels of TLR4 were higher and this was accompanied by increased renal pathology with extensive albuminuria and deterioration in antioxidant levels in OZR. In addition, OZR had increased phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.TLR4-MAPK signaling pathway is a key to the renal structural injury and dysfunction in MetS and blueberry (BB) protect against this damage by inhibiting TLR4.This is the first study to put forth a potential mechanism of TLR4-induced kidney damage in a model of MetS and to elucidate a downstream mechanism by which blueberry exert their reno-protective effects

Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-based (target SBP < 180 mm Hg) BP management. Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries. Predictors Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs