Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.

Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

Associations of Clinical Characteristics With Sudden Cardiac Arrest in People With Type 2 Diabetes With and Without Cardiovascular Disease: A Longitudinal Case-Control Study Using Routine Primary Care Data.

Objective: To assess longitudinal associations with sudden cardiac arrest (SCA) of clinical characteristics recorded in primary care in people with type 2 diabetes (T2D), both with and without cardiovascular disease (CVD).

Research Design And Methods: We performed a case-control study, with SCA case subjects with T2D from the Amsterdam Resuscitation Studies (ARREST) registry of out-of-hospital resuscitation attempts in the Dutch Noord-Holland region (2010-2020) and up to five matched (age, sex, T2D, general practitioner [GP] practice) non-SCA control subjects. We collected relevant clinical measurements, medication use, and medical history from GPs' electronic health care records.

ACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH.

Background & Aims: Recent findings reveal the importance of tryptophan-initiated de novo nicotinamide adenine dinucleotide (NAD) synthesis in the liver, a process previously considered secondary to biosynthesis from nicotinamide. The enzyme α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), primarily expressed in the liver and kidney, acts as a modulator of de novo NAD synthesis. Boosting NAD levels has previously demonstrated remarkable metabolic benefits in mouse models.

Fetal Skin Wound Healing: Key Extracellular Matrix Components and Regulators in Scarless Healing.

Fetal skin at early gestational stage is able to regenerate and heal rapidly after wounding. The exact mechanisms and molecular pathways involved in this process are however still largely unknown. The numerous differences in the skin of the early fetus versus skin in later developmental stages might provide clues for the mechanisms of scarless healing.

Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia.

Background And Objectives: Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia.

Upregulation of the AMPK-FOXO1-PDK4 pathway is a primary mechanism of pyruvate dehydrogenase activity reduction in tafazzin-deficient cells.

Barth syndrome (BTHS) is a rare disorder caused by mutations in the TAFAZZIN gene. Previous studies from both patients and model systems have established metabolic dysregulation as a core component of BTHS pathology. In particular, features such as lactic acidosis, pyruvate dehydrogenase (PDH) deficiency, and aberrant fatty acid and glucose oxidation have been identified.

Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.

Decreased nicotinamide adenine dinucleotide (NAD) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD precursor due to efficient NAD elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown.

Serum Adiponectin and Leptin Among Ghanaian Migrants in Amsterdam and Their Compatriots in Rural and Urban Ghana: The RODAM Study.

Background: The rapidly rising cardiometabolic disease (CMD) burden in urbanizing sub-Saharan African populations and among sub-Saharan African migrants in Europe likely affects serum adiponectin and leptin levels, but this has not yet been quantified.

Objectives: To compare the serum levels of adiponectin and leptin among migrant, and non-migrant (urban and rural) populations of Ghanaian descent.

Methods: Cross-sectional analysis of serum leptin and adiponectin in the multi-centre Research on Obesity and Diabetes among African Migrants (RODAM) study.

Platelets of COVID-19 patients display mitochondrial dysfunction, oxidative stress, and energy metabolism failure compatible with cell death.

Background: Alterations in platelet function have been implicated in the pathophysiology of COVID-19 since the beginning of the pandemic. While early reports linked hyperactivated platelets to thromboembolic events in COVID-19, subsequent investigations demonstrated hyporeactive platelets with a procoagulant phenotype. Mitochondria are important for energy metabolism and the function of platelets.

Young-onset dementia in memory clinics in the Netherlands: Study design and description of PRECODE-GP.

The disease trajectory and healthcare requirements of patients with young-onset dementia (YOD) differ from those of older patients. Accurate data about YOD is crucial to improve diagnosis and optimize care. PRECODE-GP aims to set up a prospective national database of patients with YOD to gain insight into the occurrence and characteristics of patients with YOD in memory clinics in the Netherlands.

Communication about diagnosis, prognosis, and prevention in the memory clinic: perspectives of European memory clinic professionals.

Background: The paradigm shift towards earlier Alzheimer's disease (AD) stages and personalized medicine creates new challenges for clinician-patient communication. We conducted a survey among European memory clinic professionals to identify opinions on communication about (etiological) diagnosis, prognosis, and prevention, and inventory needs for augmenting communication skills.

Methods: Memory clinic professionals (N = 160) from 21 European countries completed our online survey (59% female, 14 ± 10 years' experience, 73% working in an academic hospital).

Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection.

Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology.

Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC.

Inflammatory and glycolytic programs underpin a primed blood neutrophil state in patients with pneumonia.

Neutrophils are potent immune cells with key antimicrobial functions. Previous work has shown that neutrophil effector functions are mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still in the circulation in patients during infection.

Comparing the stigma experiences and comfort with disclosure in Dutch and English populations of people living with dementia.

Objectives: People living with dementia can feel hesitant disclosing their diagnosis to social networks, partly due to stigma. Little attention has been paid to the measurement of disclosure decisions and stigma, and few standardised stigma tools have been validated in languages other than English. We investigated the psychometric properties of Dutch translations of three stigma measures, and explored the stigma experiences of Dutch and English people living with dementia as well as patterns and predictors of comfort with disclosure.

Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice.

Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPR) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice.

A systematic literature review of economic evaluations and cost-of-illness studies of inherited cardiomyopathies.

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are commonly inherited heart conditions associated with a high risk of heart failure and sudden cardiac death. To understand the economic and societal disease burden, this study systematically identified and reviewed cost-of-illness (COI) studies and economic evaluations (EEs) of various interventions for HCM and DCM. A literature search was performed in MEDLINE, EMBASE, NHS EED, EconLit and Web of Science to identify COI studies and EEs published between 1 January 2010 and 28 April 2021.

[A survey study towards the opinions of clinicians, patients and care partners regarding computer tools in the memory clinic: sense or nonsense?].

Introduction: Computer tools based on artificial intelligence could aid clinicians in memory clinics by supporting diagnostic decision-making and communicating diagnosis and prognosis. We aimed to identify preferences of end-users, and barriers and facilitators for using computer tools in memory clinics.

Methods: Between July and October 2020, we invited European clinicians (n=109, age 45±10y; 47% female) to participate in an online questionnaire.

Diuretics, SGLT2 inhibitors and falls in older heart failure patients: to prescribe or to deprescribe? A clinical review.

Purpose: Both heart failure and its treatment with diuretics or SGLT2 inhibitors increase fall risk in older adults. Therefore, decisions to continue or deprescribe diuretics or SGLT2 inhibitors in older heart failure patients who have fallen are generally highly complex and challenging for clinicians. However, a comprehensive overview of information required for rationale and safe decision-making is lacking.

Lower Metabolic Potential and Impaired Metabolic Flexibility in Human Lymph Node Stromal Cells from Patients with Rheumatoid Arthritis.

Cellular metabolism is important for determining cell function and shaping immune responses. Studies have shown a crucial role for stromal cells in steering proper immune responses in the lymph node microenvironment. These lymph node stromal cells (LNSCs) tightly regulate immune tolerance.

Altered lipid metabolism in synovial fibroblasts of individuals at risk of developing rheumatoid arthritis.

Objective: Fibroblast-like synoviocytes (FLS) can augment the inflammatory process observed in synovium of patients with rheumatoid arthritis (RA). A recent transcriptomic study in synovial biopsies revealed changes in metabolic pathways before disease onset in absence of synovial tissue inflammation. This raises the question whether alterations in cellular metabolism in tissue resident FLS underlie disease pathogenesis.

Stimulating the sir2-spargel axis rescues exercise capacity and mitochondrial respiration in a Drosophila model of Barth syndrome.

Cardiolipin (CL) is a phospholipid required for proper mitochondrial function. Tafazzin remodels CL to create highly unsaturated fatty acid chains. However, when TAFAZZIN is mutated, CL remodeling is impeded, leading to mitochondrial dysfunction and the disease Barth syndrome.