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Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV− N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV− group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age‐matched controls (CN) were administered cognitive tasks during functional near‐infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small‐particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left‐dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. Highlights: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI).Functional connectivity (FC) compensation mechanism is lost in MCI.Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI.CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI.NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors. [ABSTRACT FROM AUTHOR]

Impaired cerebrovascular function contributes to the genesis of age‐related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n = 21, 33.2±7.0 years) and aged (n = 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n‐back) paradigm, oxy‐ and deoxyhemoglobin concentration changes from the frontal cortex using functional near‐infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2‐back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p < 0.05). Both impaired NVC and increased FC correlate with age‐related decline in accuracy during the 2‐back task. These findings suggest that task‐related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load. [ABSTRACT FROM AUTHOR]

Coated-platelets are a subset of highly procoagulant platelets elevated in patients with non-lacunar ischemic stroke and associated with stroke recurrence. Cross-sectional studies in controls have shown that smoking is associated with higher coated-platelet levels while chronic use of serotonin reuptake inhibitors (SSRIs), statins or aspirin is associated with lower coated-platelet levels. We now investigate if initiation of treatment with SSRIs, statins, clopidogrel, aspirin or oral anticoagulants and smoking cessation impacts coated-platelet levels at 90 days after ischemic stroke. Coated-platelet levels, reported as percent of cells converted to coated-platelets, were measured in 87 consecutive patients with stroke at baseline and repeated at 90 days. Repeated-measure ANOVA was used to determine if initiation of treatment with individual medications or smoking cessation impacted coated-platelet levels. Decreased coated-platelets levels at 90 days as compared to baseline were observed after initiation of treatment with clopidogrel (p =.0001, partial η2 = 0.17) and smoking cessation (p =.014, partial η2 = 0.10). Initiation of treatment with SSRIs, statins, aspirin or oral anticoagulants did not result in significant changes in coated-platelet potential. These novel longitudinal data suggest that clopidogrel therapy and smoking cessation attenuate coated-platelet potential at 90 days after ischemic stroke. [ABSTRACT FROM AUTHOR]

Coated-platelets are a subset of platelets with increased procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. These prothrombotic platelets are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage compared to controls. We now investigated coated-platelet synthesis in patients with symptomatic large-artery stenosis and explored the association between coated-platelet levels and stroke recurrence at 3 months in this population. Coated-platelet levels were determined in 60 patients with either acute stroke or transient ischemic attack due to large-artery stenosis and 60 controls. Recurrent stroke incidence at 3 months was stratified by tertiles of coated-platelet levels and compared among groups using a log-rank test. Large-artery stenosis patients had significantly higher coated-platelet levels than controls (mean ± SD, 42.0 ± 15.5% vs. 29.4 ± 13.5%, p < 0.0001). The 3-month cumulative incidence of recurrent stroke was 41% for the highest, 6% for the middle, and 5% for the lowest tertile of coated-platelet levels ( p = 0.0045). These results show that elevated coated-platelet levels in patients with symptomatic large-artery stenosis are associated with early stroke recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention., Methods: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry., Results: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification., Discussion: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology., Highlights: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes, and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs. CMHs are also now recognized by the National Institutes of Health as a major factor in Alzheimer's disease pathology. Moreover, the presence of CMHs is an independent risk factor for subsequent larger intracerebral hemorrhages. In this article, we review the epidemiology, detection, risk factors, clinical significance, and pathogenesis of CMHs. The potential age-related cellular mechanisms underlying the development of CMHs are discussed, with a focus on the structural determinants of microvascular fragility, age-related alterations in cerebrovascular adaptation to hypertension, the role of oxidative stress and matrix metalloproteinase activation, and the deleterious effects of arterial stiffening, increased pulse pressure, and impaired myogenic autoregulatory protection on the brain microvasculature. Finally, we examine potential treatments for the prevention of CMHs based on the proposed model of aging- and hypertension-dependent activation of the reactive oxygen species-matrix metalloproteinases axis, and we discuss critical questions to be addressed by future studies.