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Aging is associated with blood–brain barrier (BBB) breakdown and microvascular rarefaction, key contributors to cerebral neuroinflammation, hypoperfusion, and vascular cognitive impairment and dementia (VCID). Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore BBB integrity and enhance cerebrovascular function in aged mice, suggesting that circulating factors can rejuvenate the aging...
Interpretable deep learning reveals spatiotemporal MRI features of brain aging that align with neurodegenerationNARA Subscribed
Cortical thinning and atrophy are hallmarks of brain aging that have been characterized using magnetic resonance imaging (MRI). Brain aging involves many neuroanatomic features whose effects on brain structure remain unexplored. To address this challenge, we trained interpretable deep neural networks (DNNs) to estimate brain age (BA) from T 1 -weighted ( T 1 w) MRI. By identifying MRI features unapparent to humans, DNNs can fi...
Alzheimer’s disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion te...
Mortality, functional outcome, and bleeding risk after early versus delayed thrombectomyNARA Subscribed
Endovascular thrombectomy (EVT) is an established treatment for acute ischemic stroke, due to large vessel occlusion (LVO), but the optimal time window for intervention remains a subject of ongoing debate. We aimed to assess the impact of treatment timing on mortality, functional outcomes, and safety by comparing early (≤ 6 h) versus late (> 6–24 h) EVT. We conducted a systematic review and meta-analysis to evaluate the effect...
Age-related and dual task-induced gait alterations and asymmetry: optimizing the Semmelweis Study gait assessment protocolNARA Subscribed
Gait alterations are recognized as early markers of age-related decline and cognitive impairment. Dual-task assessments, which impose cognitive load while walking, provide valuable insights into gait control limitations and cognitive-motor interactions in aging populations. This study evaluates age-related and cognitive load-induced changes in gait parameters, with a particular focus on asymmetry, and aims to optimize the gait...
Chronic impairment of neurovascular coupling and cognitive decline in young survivors of severe traumatic brain injuryNARA Subscribed
Severe traumatic brain injury (TBI) leads to chronic cognitive decline, imposing a significant societal burden. The regulation of cerebral blood flow (CBF) is critical for cognitive function, and acute disruptions in CBF regulation predict poor TBI outcomes. However, the long-term effects of TBI on CBF regulation and their association with cognitive function remain poorly understood. This study aimed to investigate whether sev...
Predicting the progression of MCI and Alzheimer’s disease on structural brain integrity and other features with machine learningNARA Subscribed
Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer’s disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, th...
Chemotherapy-induced cognitive impairment (CICI), often referred to as “chemobrain,” significantly affects the quality of life in cancer survivors. Although traditionally attributed to neuronal toxicity, emerging evidence suggests a key role of cerebrovascular dysfunction in its pathogenesis. We hypothesized that paclitaxel (PTX, Taxol) treatment induces long-term cerebrovascular dysfunction, including microvascular rarefactio...
Chemotherapy-related cognitive impairment, commonly referred to as “chemobrain,” significantly affects cancer survivors’ quality of life, yet its underlying mechanisms remain unclear. Most chemotherapeutic agents cannot cross the blood–brain barrier (BBB), yet they cause central nervous system side effects, suggesting alternative pathways of toxicity. Given that these drugs interact with the cerebrovascular endothelium at thei...
The increasing number of cancer survivors has brought heightened attention to the side effects of cancer therapies, including chemotherapy-related cognitive impairment (CRCI, commonly referred to as “chemobrain”). Cisplatin and methotrexate, commonly used first-line chemotherapeutics in gynecologic oncology for cancers such as breast, ovarian, and bladder cancer, are clinically associated with long-term cognitive deficits. Bui...
Chemotherapy-induced cognitive impairment (CICI), commonly referred to as “chemobrain,” is a frequent and debilitating side effect experienced by cancer survivors treated with paclitaxel (PTX). Preclinical models have shown that PTX promotes cerebromicrovascular endothelial cell senescence, leading to chronic blood–brain barrier (BBB) disruption and neuroinflammation. Conversely, the elimination of senescent cells through seno...
The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in agingNARA Subscribed
Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of...
Cerebral microhemorrhages (CMHs) are of paramount importance as they not only signify underlying vascular pathology but also have profound implications for cognitive function and neurological health, serving as a critical indicator for the early detection and management of vascular cognitive impairment (VCI). This study aimed to investigate the effects of hypertension-induced CMHs on gait dynamics in a mouse model, focusing on...
Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood–brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperinte...
Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhagesNARA Subscribed
Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closel...
DNA methylation clock DNAmFitAge shows regular exercise is associated with slower aging and systemic adaptationNARA Subscribed
DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33–88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO 2 max ( ρ = 0.2, p = 6.4E − 4, r = 0.19, p = 1.2E − 3), Jumpmax...
Age-related decline in circulating IGF-1 associates with impaired neurovascular coupling responses in older adultsNARA Subscribed
Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) to the increased oxygen and energy requirements of active brain regions via neurovascular coupling (NVC) contributes to the genesis of age-related cognitive impairment. Aging is associated with marked deficiency in the vasoprotective hormone insulin-like growth factor-1 (IGF-1). Preclinical studies on animal models of aging suggest that circulating IGF-1 de...