Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.

Female sex, age, and APOE4 genotype are the greatest risk factors for Alzheimer's disease. Using a translational perimenopause mouse model based on human Stages of Reproductive Aging Works (STRAW) criteria, we investigated the impact of APOE genotype on female midlife endocrine aging, peripheral metabolic indicators, brain bioenergetic pathways, mitochondrial function, neuroimmune activation, and myelination. Compared to APOE3 females, APOE4 females exhibited accelerated endocrine aging that was coincident with failure to mount adaptive bioenergetic reprogramming and significant decline in mitochondrial function that were coupled with increased immune activation and demyelination in brain.

Cognitive impairment and p-tau217 are high in a vascular patient cohort.

Introduction: Vascular comorbidities are modifiable contributors to cognitive impairment and Alzheimer's disease (AD), yet brain health outcomes are rarely evaluated in cardiovascular patients.

Methods: This study prospectively evaluated cognition and AD pathology in 162 community-dwelling adults with asymptomatic cardiovascular disease who did not have a clinical diagnosis of dementia or cognitive impairment.

Results: Twenty-nine percent of the cohort had Montreal Cognitive Assessment (MoCA) scores indicative of cognitive impairment or dementia after adjusting for age, sex, and education based on National Alzheimer's Coordinating Center normative data.

Comparative Analysis of SiMoA and Ella Immunoassay Platforms for Measuring Serum Neurofilament Light Chain Levels in ATTRv With Polyneuropathy and Presymptomatic Carriers.

Background: Neurofilament light chains (NfL) represent reliable serum biomarkers of neuroaxonal injury. Due to their low serum levels, precise detection methods are critical. This study aimed to scrutinize the comparability of two techniques: Single Molecule Array (SiMoA) and Ella automated immunoassay, analyzing serum NfL levels in ATTRv presymptomatic subjects and polyneuropathy patients.

Multisystem failure, tipping points, and risk of Alzheimer's disease.

Introduction: Medical conditions including obesity, diabetes, hyperlipidemia, and depression significantly increased risk of Alzheimer's disease (AD). However, effect of their duration, influenced by non-modifiable factors like chromosomal sex and apolipoprotein E (APOE) genotype, remains unclear.

Methods: Data from 5644 UKBiobank participants were analyzed using Cox regression model to identify critical tipping points based on age of onset, risk factor (RF) duration and their interaction with sex and APOE genotype.

Elevated serum concentrations of GFAP in hereditary transthyretin amyloidosis since pre-symptomatic stages.

Background: Hereditary transthyretin amyloidosis (ATTRv) is a rare disorder caused by pathogenic TTR gene variants. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are potential biomarkers for astrocyte activation and neuroaxonal damage, respectively. This study investigates serum GFAP (sGFAP) and NfL (sNfL) levels in ATTRv patients, pre-symptomatic subjects, and healthy controls (HCs) to evaluate their utility as biomarkers of disease progression and CNS involvement.

Combination therapy targeting Alzheimer's disease risk factors is associated with a significant delay in Alzheimer's disease-related cognitive decline.

Background: Alzheimer's disease (AD) cognitive decline can be a major contributor to loss of independent living. Therapeutic strategies that alter the course of cognitive deterioration have the potential to sustain activities of daily living, promote quality of life, and delay transition to nursing-home care.

Methods: We performed longitudinal linear regression analysis of National Alzheimer's Coordinating Center (NACC) cognitive data from 7653 mild dementia AD participants at baseline with at least one medication for diabetes (DBMD), lipid-lowering (LIPL), anti-hypertensive (AHTN), and non-steroidal anti-inflammatory (NSD) medications or any combination in 5684 (74%) participants and in 1969 (26%) participants with no study-relevant prescriptions over 10 years.

Sudoscan in ATTRv Amyloidosis: A Potential Marker of Disease Progression?

Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a severe, autosomal dominant disease resulting from multisystemic extracellular deposition of amyloid fibrils, leading to progressive organ damage and death. Sudoscan is a reproducible tool investigating sweat gland function and, indirectly, small nerve fiber impairment. The aim of this study was to evaluate any changes over time in electrochemical skin conductance (ESC) measured by Sudoscan in a cohort of late-onset patients with ATTRv from a single Italian center.

Transthyretin amyloid deposition in the ligamentum flavum of an Italian cohort of patients with lumbar spinal stenosis.

Transthyretin amyloidosis (ATTR amyloidosis) is a rare systemic disorder characterized by the extracellular deposition of amyloid fibrils, which can affect multiple tissues. Lumbar spinal stenosis (LSS), a condition involving narrowing of the lumbar spinal canal, has been frequently associated with amyloid deposition in the ligamentum flavum (LF). This study aimed to evaluate the prevalence of ATTR deposits in LF samples obtained from patients undergoing LSS surgery at two Italian centers.

Automated pupillometry is a predictor of outcome of stroke patients: an observational, prospective, cohort study.

Automated pupillometry (AP) is a rapid, non-invasive tool to assess the pupillary light reflex, extensively used for monitoring patients with traumatic brain injury. In acute ischaemic stroke, quantitative tools to monitor neurological status and predict outcome are lacking. This study aims to evaluate the ability of AP to predict stroke outcome, defined through the modified Rankin Scale (mRS) scores.

Neurofibrillary tangles predict dementia in patients with carotid stenosis.

Objective: There is growing appreciation that extracranial carotid atherosclerotic disease (ECAD) is associated with increased dementia risk. Despite this, clinical management of ECAD does not involve evaluation for cognitive outcomes or risk stratification for dementia. One impediment to studying and improving clinical care for this cohort (roughly 10% of adults aged >60 years) is that factors to identify patients with ECAD at risk for dementia are not known.

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study.

Background: Hereditary amyloid transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, inherited, multisystemic, progressive adult-onset disease, affecting sensorimotor nerves, and various organs. It is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate, forming amyloid fibrils. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, designed to enter hepatocytes and selectively target TTR mRNA to reduce both variant TTR and wild-type TTR (wt).

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer's risk population: A retrospective analysis.

Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes.

Basic psychological needs satisfaction, coping functions, and emotional experiences in competitive athletes: a multi-states theory perspective.

The aim of the study was to investigate the relationship between basic psychological needs satisfaction, coping functions, cognitive appraisals, emotions, and psychobiosocial experiences in competitive athletes. Multi-states (MuSt) theory was used as the theoretical framework. The study involved a convenience sample of 183 Italian athletes (102 men), aged 16 to 48 years (M = 24.

IgM Flare in Anti-MAG Neuropathy Post Rituximab Treatment: A Clinical Case and a Systematic Review of the Literature.

Background/objectives: Anti-MAG polyneuropathy is a demyelinating peripheral neuropathy associated with IgM monoclonal gammopathies, particularly MGUS (monoclonal gammopathy of undetermined significance) and Waldenström macroglobulinemia. It is characterized by a subacute onset of distal sensory symptoms, with distal motor dysfunction typically appearing only in the later stages of the disease. The condition is caused by the presence of autoantibodies directed against myelin-associated glycoprotein, a structural protein of myelin.

Serum Biomarkers in Transthyretin Amyloidosis: An Overview of Neurofilaments, Cardiac, Renal, and Gastrointestinal Involvement.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a genetic disorder characterized by the deposition of misfolded transthyretin (TTR) protein in tissues, resulting in progressive dysfunction of multiple organs, including the nervous system, heart, kidneys, and gastrointestinal (GI) tract. Noninvasive serum biomarkers have become key tools for diagnosing and monitoring ATTRv. This review examines the role of available biomarkers for neurological, cardiac, renal, gastrointestinal, and multisystemic involvement in ATTRv.

Cognitive appraisals linking dispositional mindfulness to athletes' emotions: a multi-states theory approach.

Purpose: The aim of the study was to examine the relationship between dispositional mindfulness, cognitive appraisals, emotions, and psychobiosocial experiences in athletes within the framework of multi-states (MuSt) theory.

Method: A convenience sample of 334 Italian athletes (188 men and 146 women), aged 18-48 years ( = 24.77,  = 7.

Asymptomatic carotid artery stenosis is associated with increased Alzheimer's disease and non-Alzheimer's disease dementia risk.

Background: In the absence of a cerebrovascular accident, whether asymptomatic extracranial carotid atherosclerotic disease (aECAD) affects Alzheimer's disease (AD) and non-AD dementia risk is not clear. Understanding whether aECAD is associated with an increased risk for AD is important as it is present in roughly 10% of the population over 60 and could represent a modifiable risk factor for AD and non-AD dementia.

Methods: This retrospective cohort study analysed Mariner insurance claims.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study.

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score).

Automated Pupillometry Is Able to Discriminate Patients with Acute Stroke from Healthy Subjects: An Observational, Cross-Sectional Study.

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS).

The power of coaches' emotions: A case study on how coaches' facial expressions impact performance of young female synchronized ice-skaters.

Objectives: The present study aimed to investigate the impact of coaches' pleasant and unpleasant facial expressions on affects and team performance of young elite female synchronized ice-skaters.

Methods: Initially, the coach provided a neutral explanation of the exercise, which was followed by the athletes' execution. The ice-skaters then received either pleasant or unpleasant feedback from the coach, completed two questionnaires, and performed the exercise again.