The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.

Introduction: The harmful alga Karenia brevis (K. brevis) releases brevetoxins (PbTx) that cause respiratory and neurological symptoms. The apolipoprotein E (APOE) ε4 allele has been linked to poor neurological outcomes after exposure to environmental toxicants.

Baseline serum brain-derived neurotrophic factor association with future cognition in community-dwelling older adults undergoing annual memory screening.

Objectives: It has been shown that peripheral measures of brain-derived neurotrophic factor (BNDF), an important neurotrophin instrumental to the biology of learning, may contribute to predicting cognitive decline. However, the two primary forms of BDNF, mature (mBDNF) and pro (proBDNF), and how they contribute to cognition longitudinally has not been well studied.

Methods: Eighty-two older adults (average age 72.

Interleukin 10 (IL10) promoter region polymorphism is associated with IL10 serum concentrations and processing speed in healthy community-dwelling older adults.

Inflammation is repressed by interleukin 10 (IL10), a potent anti-inflammatory cytokine, and unchecked inflammation can have detrimental effects on cognition. In healthy older adults enrolled in the Australian Research Council Longevity Intervention (ARCLI) cohort we explored whether a known functional single nucleotide polymorphism (SNP) in the promoter region of IL10, -1082 G/A (rs1800896), was associated with reaction times on computerized cognitive testing that included elements of processing speed (i.e.

Liver and inflammatory biomarker relationships to depression symptoms in healthy older adults.

Introduction: Early identification and management of physical and mental illness is vital to maintain quality of life as we age. Markers of peripheral inflammation and liver function show elevations with aging, and are also associated with depression symptoms, suggesting a similar pattern in both aging and clinical groups.

Methods: The current study examined the relationship between such markers and measures of depression/negative mood in 284 healthy older adults using data from the Australian Research Council Longevity Intervention (ARCLI).

supplementation has no effect on serum brain-derived neurotrophic factor levels but beneficially modulates nuclear factor kappa B and cyclic AMP response element-binding protein levels in healthy elderly subjects.

Background And Aim: is an Ayurvedic herb that has been used for multiple conditions, most notably to augment cognition, particularly memory and attention. Multiple mechanisms, including raising brain-derived neurotrophic factor (BDNF), have been proposed and investigated in animal models that require translational studies in humans.

Methods: Bacopa was administered in an open-labeled study to cognitively healthy controls over a 3-month period.

APOE ε4 and Alzheimer's disease diagnosis associated differences in L-carnitine, GBB, TMAO, and acylcarnitines in blood and brain.

Background: The apolipoprotein E (APOE) ε4 allele, involved in fatty acid (FA) metabolism, is a major genetic risk factor for Alzheimer's disease (AD). This study examined the influence of APOE genotypes on blood and brain markers of the L-carnitine system, necessary for fatty acid oxidation (FAO), and their collective influence on the clinical and pathological outcomes of AD.

Methods: L-carnitine, its metabolites γ-butyrobetaine (GBB) and trimethylamine-n-oxide (TMAO), and its esters (acylcarnitines) were analyzed in blood from predominantly White community/clinic-based individuals (n = 372) and in plasma and brain from the Religious Order Study (ROS) (n = 79) using liquid chromatography tandem mass spectrometry (LC-MS/MS).

Characterization of immune profile in an aging multiple sclerosis clinic population.

Background: There is limited data regarding adaptive immunity in older persons with Multiple Sclerosis (MS).

Objective: The aim of the present study was to quantify adaptive immune cells in younger (age less than 50) and older (age greater than 50) with MS in the context of clinical parameters (EDSS, 25-foot walk, SDMT). Subjects were either Untreated (no MS medications in 6 months), taking Injectables (interferons or glatiramer acetate), or Other approved MS treatments.

Sex-specific differences in plasma lipid profiles are associated with Gulf War Illness.

Background: Nearly 250,000 veterans from the 1990-1991 Gulf War have Gulf War Illness (GWI), a condition with heterogeneous pathobiology that remains difficult to diagnose. As such, availability of blood biomarkers that reflect the underlying biology of GWI would help clinicians provide appropriate care to ill veterans. In this study, we measured blood lipids to examine the influence of sex on the association between blood lipids and GWI diagnosis.

Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model.

Gulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War (GW), who suffer from symptoms that reflect ongoing mitochondria dysfunction. Brain mitochondria bioenergetics dysfunction in GWI animal models corresponds with astroglia activation and neuroinflammation. In a pilot study of GW veterans (n = 43), we observed that blood nicotinamide adenine dinucleotide (NAD) and sirtuin 1 (Sirt1) protein levels were decreased in the blood of veterans with GWI compared to healthy GW veterans.

Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease.

Introduction: This clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy.

Methods: 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini-Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double-blind, sham-controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting.

A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness.

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins.

Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

Objective: Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6).

Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment.

Background: Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects.

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease.

This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers.

Lymphocytic esophagitis: Report of three cases and review of the literature.

Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema ("spongiosis"). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis.

Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-Amyloid.

We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period.

Hospital bed occupancy: more than queuing for a bed.

Timely access to safe hospital care remains a major concern. Target bed-occupancy rates have been proposed as a measure of the ability of a hospital to function safely and effectively. High bed-occupancy rates have been shown to be associated with greater risks of hospital-associated infection and access block and to have a negative impact on staff health.

Serum Abeta levels as predictors of conversion to mild cognitive impairment/Alzheimer disease in an ADAPT subcohort.

Recent evidence suggests an association of beta-amyloid (Abeta) with vascular risk factors and the medications to treat them, which could potentially obfuscate the usefulness of Abeta for prediction of mild cognitive impairment (MCI) or Alzheimer disease (AD). In a subcohort from the Alzheimer's Disease Anti-inflammatory Prevention Trial (enriched for family history of AD), we investigated whether systolic blood pressure, total cholesterol, triglycerides, serum creatinine, apolipoprotein E, and use of statins and antihypertensives influenced the predictive value of serum Abeta for MCI/AD during a 2-year period. We collected blood samples to quantify serum Abeta from cognitively normal participants (n = 203) at baseline and ascertained the outcome of MCI/AD (n = 24) for a period of approximately 2 years.

Cross validation of the Montreal Cognitive Assessment in community dwelling older adults residing in the Southeastern US.

Objective: Cross validation study of the MoCA for the detection of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) in a community-based cohort residing in the Southeastern United States.

Methods: One hundred and eighteen English-speaking older adults, who underwent diagnostic evaluation as part of an on-going prospective study, were administered the MoCA and MMSE. Twenty were diagnosed with AD, 24 met criteria for amnestic MCI and 74 were considered cognitively normal.

Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in Alzheimer's disease.

A continuous inflammatory state is associated with Alzheimer's disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Abeta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis.

The influence of diagnosis, intra- and inter-person variability on serum and plasma Abeta levels.

Evidence suggests that high peripheral beta-amyloid (Abeta)(1-40) levels and low ratios of Abeta(1-42)/Abeta(1-40) are associated with increased risk for Alzheimer's disease (AD). In this cross-sectional design, serum and plasma samples from 67 AD patients and 146 controls (similar in age and gender) were evaluated using Abeta(1-40) and Abeta(1-42) ELISA. Coefficient of variance was calculated for intra- and inter-person variability of Abeta(1-40) and Abeta(1-42).

A case of hyoscine-related oesophagitis.

We describe a previously unreported association between hyoscine hydrobromide and severe oesophagitis, with ulceration visible almost to the submucosa in the distal oesophagus. The condition resolved with cessation of tablets and 2 months' treatment with a proton-pump inhibitor.