Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.

Altered energy metabolism in Alzheimer's disease (AD) is a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are implicated in multiple neurodegenerative diseases. Although numerous studies have investigated global changes in brain metabolism, redox status, gene expression and epigenetic markers in AD, the intricate interplay between different metabolic processes, particularly in astrocytes, remains poorly understood.

The magnitude of exercise-induced progenitor cell mobilisation and extravasation is positively associated with cardiorespiratory fitness.

CD34 progenitor cells with angiogenic capabilities traffic into blood during exercise and extravasate afterwards but the magnitude of this response varies between people. We examined whether exercise-induced progenitor cell trafficking is influenced by cardiorespiratory fitness (maximum oxygen uptake; ). Ten males (age: 23 ± 3 years; : 61.

The Relationship Between Physical Activity and Non-Modifiable Risk Factors on Alzheimer's Disease and Brain Health Markers: A UK Biobank Study.

Background: Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer's disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition.

Objective: The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition.

Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis.

Introduction: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations.

Effects of the COVID-19 associated United Kingdom lockdown on physical activity in older adults at high risk of cardiovascular disease: a mixed methods perspective from the MedEx-UK multicenter trial.

Introduction: Physical inactivity and sedentary behaviour are linked to increased risk of cardiovascular disease, infections and dementia, as well as placing a significant economic burden on healthcare systems. The implementation of COVID-19 pandemic lockdown measures aimed at reducing virus transmission posed challenges to the opportunity to be physically active. This study investigates how the first UK COVID-19 lockdown affected objectively measured physical activity in older adults at higher risk of cardiovascular disease.

Inhibitory control mediates the effect of high intensity interval exercise on food choice.

Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite, food choices, and cognitive processes, and the mediating role of cognitive functioning, namely inhibitory control, working memory, cognitive flexibility and decision making. We compared the effects of high-intensity interval exercise (HIIE) to a resting condition on appetite and food choices, using visual analogue rating scales and a computerised portion selection task.

The role of ADAM10 in astrocytes: Implications for Alzheimer's disease.

Much of the early research into AD relies on a neuron-centric view of the brain, however, evidence of multiple altered cellular interactions between glial cells and the vasculature early in AD has been demonstrated. As such, alterations in astrocyte function are widely recognized a contributing factor in the pathogenesis of AD. The processes by which astrocytes may be involved in AD make them an interesting target for therapeutic intervention, but in order for this to be most effective, there is a need for the specific mechanisms involving astrocyte dysfunction to be investigated.

Inflammation in first-episode psychosis: The contribution of inflammatory biomarkers to the emergence of negative symptoms, a systematic review and meta-analysis.

Objective: To provide a comprehensive analysis of cytokine perturbations in antipsychotic-naïve first-episode psychosis (FEP) populations and assess the relationship between inflammatory biomarkers and negative symptom severity.

Methods: A systematic review and meta-analysis following PRISMA guidelines were conducted. A total of 1042 records were identified via systematic search of EMBASE, MEDLINE and APA PsycInfo databases.

Amyloid-β precursor protein processing and oxidative stress are altered in human iPSC-derived neuron and astrocyte co-cultures carrying presenillin-1 gene mutations following spontaneous differentiation.

Introduction: Presenilin-1 (PSEN1) gene mutations are the most common cause of familial Alzheimer's disease (fAD) and are known to interfere with activity of the membrane imbedded γ-secretase complex. PSEN1 mutations have been shown to shift Amyloid-β precursor protein (AβPP) processing toward amyloid-β (Aβ) 1-42 production. However, less is known about whether PSEN1 mutations may alter the activity of enzymes such as ADAM10, involved with non-amyloidogenic AβPP processing, and markers of oxidative stress.

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: protocol for the MedEx-UK randomised controlled trial.

Introduction: Dementia prevalence continues to increase, and effective interventions are needed to prevent, delay or slow its progression. Higher adherence to the Mediterranean diet (MedDiet) and increased physical activity (PA) have been proposed as strategies to facilitate healthy brain ageing and reduce dementia risk. However, to date, there have been no dementia prevention trials in the UK focussed on combined dietary and PA interventions.

Age, BMI, and inflammation: Associations with emotion recognition.

Experimental studies show that inflammation impairs the ability to interpret the mental state of another person, denoted theory of mind (ToM). The current study attempted a conceptual replication in states associated with elevated low-grade inflammation, i.e.

Exercise as a protective mechanism against the negative effects of oxidative stress in first-episode psychosis: a biomarker-led study.

First-episode psychosis (FEP) is a psychiatric disorder, characterised by positive and negative symptoms, usually emerging during adolescence and early adulthood. FEP represents an early intervention opportunity for intervention in psychosis. Redox disturbance and subsequent oxidative stress have been linked to the pathophysiology of FEP.

Tai Chi is an effective form of exercise to reduce markers of frailty in older age.

Frailty affects the quality of life of older age adults by limiting mobility, reducing physiological reserve and reducing independence. The frailty phenotype is typically characterised by exhaustion, loss or lack of physical activity, weight loss and weakness, although more recently there have been proposals to extend the frailty criteria to include physiological characteristics such as inflammation, oxidative stress and vascular function. Exercise has the potential to prevent, delay or even reverse frailty, but not all exercise is perceived as suitable for an older age population.

Designing a feasible exercise intervention in first-episode psychosis: Exercise quality, engagement and effect.

First-episode psychosis (FEP) is the first presentation of a psychotic disorder that usually propagates during early adulthood. FEP represents an important early intervention point to attenuate the metabolic risks associated with psychosis and its treatment. Exercise has potential to improve metabolic and functional outcome, but engaging this population in regular exercise is typically difficult.

The effect of age and obesity on platelet amyloid precursor protein processing and plasma markers of oxidative stress and inflammation.

Introduction: Advancing age is a major risk factor for a range of diseases such as, cardiovascular disease, diabetes, cancer and neurodegenerative diseases. In addition, over a third of the population are overweight and obesity is becoming more prevalent in younger people. Ageing and obesity are both linked to a chronic proinflammatory state and elevated oxidative stress, which have both been implicated in cardiovascular and neurodegenerative diseases.

Inflammation Mediates Body Weight and Ageing Effects on Psychomotor Slowing.

Inflammation (immune system activation) affects neuronal function and may have consequences for the efficiency and speed of functional brain processes. Indeed, unusually slow psychomotor speed, a measure predictive of behavioural performance and health outcomes, is found with obesity and ageing, two conditions also associated with chronic inflammation. Yet whether inflammation is the mediating factor remains unclear.

Loneliness in healthy young adults predicts inflammatory responsiveness to a mild immune challenge in vivo.

The established link between loneliness and poor health outcomes may stem from aberrant inflammatory regulation. The present study tested whether loneliness predicted the inflammatory response to a standardised in vivo immune challenge. Using a within-subjects double blind placebo-controlled design, 40 healthy men (mean age = 25, SD = 5) received a Salmonella Typhi vaccination (0.

Selective effects of acute low-grade inflammation on human visual attention.

Illness is often accompanied by perceived cognitive sluggishness, a symptom that may stem from immune system activation. The current study used electroencephalography (EEG) to assess how inflammation affected three different distinct attentional processes: alerting, orienting and executive control. In a double-blinded placebo-controlled within-subjects design (20 healthy males, mean age = 24.

Mediterranean diet adherence and cognitive function in older UK adults: the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) Study.

Background: In Mediterranean countries, adherence to a traditional Mediterranean dietary pattern (MedDiet) is associated with better cognitive function and reduced dementia risk. It is unclear if similar benefits exist in non-Mediterranean regions.

Objectives: The aims of this study were to examine associations between MedDiet adherence and cognitive function in an older UK population and to investigate whether associations differed between individuals with high compared with low cardiovascular disease (CVD) risk.

Role of magnetic resonance spectroscopy in cerebral glutathione quantification for youth mental health: A systematic review.

Aim: Oxidative stress is strongly implicated in many psychiatric disorders, which has resulted in the development of new interventions to attempt to perturb this pathology. A great deal of attention has been paid to glutathione, which is the brain's dominant antioxidant and plays a fundamental role in removing free radicals and other reactive oxygen species. Measurement of glutathione concentration in the brain in vivo can provide information on redox status and potential for oxidative stress to develop.

Depression in Alzheimer's Disease: An Alternative Role for Selective Serotonin Reuptake Inhibitors?

Depression is a common co-morbidity seen in people with Alzheimer's disease (AD). However, the successful treatment of depressive symptoms in people with AD is rarely seen. In fact, multiple randomized controlled trials have shown selective serotonin reuptake inhibitors (SSRIs), the current best recommended treatment for depression, to be ineffective in treating depressive symptoms in people with AD.

Acute aerobic exercise induces a preferential mobilisation of plasmacytoid dendritic cells into the peripheral blood in man.

Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise.

Low-grade inflammation decreases emotion recognition - Evidence from the vaccination model of inflammation.

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment.

Preliminary evidence of reductive stress in human cytotoxic T cells following exercise.

This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained [ n = 9, means ± SD: age 28 ± 5 yr; (body mass index) BMI 23.2 ± 2.6 kg/m; V̇o (maximal oxygen intake)56.