improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice.

Background: Alzheimer's disease (AD) is a growing public health problem in the aging population, with limited treatment options. We previously reported that herb water extract (CAW) attenuates cognitive decline in murine models of AD and aging.

Objective: To explore changes in the hippocampal metabolome associated with CAW's modulation of cognitive function and amyloid-β (Aβ) plaque load in aged Tg2576 and wild-type (WT) mice.

Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice.

Extracts of the plant can enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study, we explore the effects of AA on brain mitochondrial function, antioxidant response and cognition in a beta-amyloid (Aβ)-overexpressing 5xFAD mouse line.

Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts.

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear.

The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.

Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.

Sex Differences in Basal Cortisol Levels Across Body Fluid Compartments in a Cross-sectional Study of Healthy Adults.

Context: Many studies have moved toward saliva and peripheral blood sampling for studying cortisol, even in relation to disorders of the brain. However, the degree to which peripheral cortisol reflects central cortisol levels has yet to be comprehensively described. Data describing the effect that biological characteristics such as age and sex have on cortisol levels across compartments is also limited.

Parkinson's disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction.

Parkinson's disease (PD) is a complex multisystem disorder clinically characterized by motor, non-motor, and premotor manifestations. Pathologically, PD involves neuronal loss in the substantia nigra, striatal dopamine deficiency, and accumulation of intracellular inclusions containing aggregates of α-synuclein. Recent studies demonstrate that PD is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA).

ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults: A Randomized Clinical Trial.

Importance: Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, including Alzheimer disease, may be preventable through ω-3 treatment.

Objective: To determine whether ω-3 treatment reduces WML accumulation in older adults without dementia harboring WMLs and with suboptimal ω-3 status.

Design, Setting, And Participants: This quadruple-blinded, placebo-controlled, randomized clinical trial with treatment stratification by apolipoprotein E ε4 allele (APOE*E4) carrier status used linear mixed-effects models to estimate mean annual change between groups.

The Time Course of Changes in Prefrontal Cortex Activity During Walking in People With Parkinson's Disease.

Background: Walking abnormalities in people with Parkinson's disease (PD) are characterized by a shift in locomotor control from healthy automaticity to compensatory, executive control, mainly located in the prefrontal cortex (PFC). Although PFC activity during walking increases in people with PD, the time course of PFC activity during walking and its relationship to clinical or gait characteristics is unknown.

Objective: To identify the time course of PFC activity during walking in people with PD.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease.

Boron-Silicon Alloy Nanoparticles as a Promising New Material in Lithium-Ion Battery Anodes.

Silicon's potential as a lithium-ion battery (LIB) anode is hindered by the reactivity of the lithium silicide (Li Si) interface. This study introduces an innovative approach by alloying silicon with boron, creating boron/silicon (BSi) nanoparticles synthesized via plasma-enhanced chemical vapor deposition. These nanoparticles exhibit altered electronic structures as evidenced by optical, structural, and chemical analysis.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Background And Objectives: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.

Amelioration of age-related cognitive decline and anxiety in mice by extract varies by sex, dose and mode of administration.

A water extract (CAW) of the Ayurvedic plant administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.

Fluoro-Ethylene-Carbonate Plays a Double-Edged Role on the Stability of Si Anode-Based Rechargeable Batteries During Cycling and Calendar Aging.

The energy storage density of Li-ion batteries can be improved by replacing graphite anodes with high-capacity Si-based materials, though instabilities have limited their implementation. Performance degradation mechanisms that occur in Si anodes can be divided into cycling stability (capacity retention after repeated battery cycles) and calendar aging (shelf life). While cycling instabilities and improvement strategies have been researched intensively, there is little known about the underlying mechanisms that cause calendar aging.

Surface and Bulk Stabilization of Silicon Anodes with Mixed-Multivalent Additives: Ca(TFSI) and Mg(TFSI).

Silicon is drawing attention as an emerging anode material for the next generation of lithium-ion batteries due to its higher capacity compared with commercial graphite. However, silicon anions formed during lithiation are highly reactive with binder and electrolyte components, creating an unstable SEI layer and limiting the calendar life of silicon anodes. The reactivity of lithium silicide and the formation of an unstable SEI layer are mitigated by utilizing a mixture of Ca and Mg multivalent cations as an electrolyte additive for Si anodes to improve their calendar life.

Mode of administration influences plasma levels of active compounds in 5xFAD mice while markers of neuroinflammation remain unaltered.

Introduction: A water extract of (L.) Urban [Apiaceae] (CAW) has demonstrated cognitive-enhancing effects in mouse models of Alzheimer's disease and aging, the magnitude of which is influenced by whether CAW is delivered in the drinking water or the diet. These cognitive benefits are accompanied by improvements in oxidative stress and mitochondrial function in the brain, two pathways related to the neuroinflammatory response.

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-β Toxicity.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of () that protect against Aβ cytotoxicity in vitro. has been associated with improving mental health and cognitive function, with potential use in Alzheimer's disease.

Amelioration of age-related cognitive decline and anxiety in mice by extract varies by sex, dose and mode of administration.

We have previously reported that a water extract (CAW) of the Ayurvedic plant administered in drinking water can improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here we compared the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.

Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers.

There is great interest in developing clinical biomarker assays that can aid in non-invasive diagnosis and/or monitoring of human diseases, such as cancer, cardiovascular disease, and neurological diseases. Yet little is known about the longitudinal stability of miRNAs in human plasma. Here we assessed the intraindividual longitudinal stability of miRNAs in plasma from healthy human adults, and the impact of common factors (e.

Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies.

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.

Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial.

Background: Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease.

Methods: We report a 36-week, randomised, double-blind, placebo-controlled study of NLY01 in participants with early untreated Parkinson's disease conducted at 58 movement disorder clinics in the USA.

Bioanalytical method validation and application to a phase 1, double-blind, randomized pharmacokinetic trial of a standardized (L.) Urban water extract product in healthy older adults.

is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults.

Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health.

Lipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF.

Lifelong Association of Disorders Related to Military Trauma with Subsequent Parkinson's Disease.

Background: Trauma-related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging as risk factors for Parkinson's disease (PD), but their association with development of PD and independence from comorbid disorders remains unknown.

Objective: To examine TBI and PTSD related to early trauma in military veterans using a case-control study.

Methods: PD was identified by International Classification of Diseases (ICD) code, recurrent PD-specific prescriptions, and availability of 5+ years of earlier records.