Cerebral circulation - cognition and behavior最新文献

{"title":"Identification of novel cerebral small vessel disease biomarkers in blood using proteomics","authors":"Claudia Satizabal ,&nbsp;Tiffany Kautz ,&nbsp;Mohsen Sharifi Tabar ,&nbsp;Rebecca Bernal ,&nbsp;Julia Mathews ,&nbsp;Muralidharan Sargurupremraj ,&nbsp;Vinu Philip ,&nbsp;Habil Zare ,&nbsp;Haritha Vardhini Katragadda ,&nbsp;Qiong Yang ,&nbsp;Charles DeCarli ,&nbsp;Pauline Maillard ,&nbsp;Mohamad Habes ,&nbsp;Sudha Seshadri","doi":"10.1016/j.cccb.2024.100302","DOIUrl":"10.1016/j.cccb.2024.100302","url":null,"abstract":"<div><h3>Introduction</h3><p>Identifying novel cerebral small vessel disease (cSVD) biomarkers in blood is critical to advance therapeutic and preventive strategies for Vascular Contributions to Cognitive Impairment and Dementia (VCID). This exploratory analysis aimed to identify novel blood-based markers of cSVD using proteomics in a Hispanic sample. This is critical, as most biomarker discovery has focused on non-Hispanic Whites, despite increased cardiometabolic risk and cognitive impairment among minoritized populations.</p></div><div><h3>Methods</h3><p>We included 107 dementia-free Mexican American participants from the MarkVICD-1 San Antonio site (73% women, mean age 70 ±7 years, Table 1). Participants provided fasting blood samples and underwent a comprehensive clinical and neuroimaging evaluation. Serum aliquots were shipped to Olink for proteomic profiling with the Explore 3072 panel. Normalized protein levels were related to cSVD markers, including White Matter Hyperintensities (WMH), Peak-with of Skeletonized Mean Diffusivity (PSMD), and Free Water (FW), using linear regression models adjusting for age, age2, sex, and total intracranial volume. P-values were corrected using False Discovery Rate (FDR) to account for multiple testing.</p></div><div><h3>Results</h3><p>We identified 36, and 128 proteins significantly associated with PSDM, and FW, respectively (Figure 1). The strongest associations were seen for elevated neurogranin with higher PSMD (Beta ±SE, 0.20 ±0.04, FDR=0.005) and FW (0.23 ±0.04, FDR=0.002), and Cartilage Intermediate Layer Protein (CILP) with higher PSMD (0.07 ±0.014, FDR=0.005). Neurogranin is a marker of synaptic dysfunction and CSF levels have shown potential as a predictor of cognitive decline. CILP may antagonize TGFB1 and IGF1 and has been related to mortality in patients with heart failure.</p></div><div><h3>Discussion</h3><p>Our results uncovered multiple novel blood-based cSVD biomarkers for risk stratification in VCID studies, including neurogranin and CILP. Further studies are needed to confirm these findings in larger samples.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100302"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266624502400103X/pdfft?md5=5493fbd4d4972657512ebca96d41c069&pid=1-s2.0-S266624502400103X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia","authors":"Lauren Edwards ,&nbsp;Kelsey R. Thomas ,&nbsp;Alexandra J. Weigand ,&nbsp;Emily C. Edmonds ,&nbsp;Alexandra L. Clark ,&nbsp;Einat K. Brenner ,&nbsp;Sarah J. Banks ,&nbsp;Paul E. Gilbert ,&nbsp;Daniel A. Nation ,&nbsp;Lisa Delano-Wood ,&nbsp;Mark W. Bondi ,&nbsp;Katherine J. Bangen ,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1016/j.cccb.2024.100206","DOIUrl":"https://doi.org/10.1016/j.cccb.2024.100206","url":null,"abstract":"<div><p>This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP – diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000072/pdfft?md5=87d61e191aec7335c7caaff1513f0432&pid=1-s2.0-S2666245024000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low serum HDL-cholesterol is associated with increased risk of the subcortical small vessel type of dementia","authors":"Elin Axelsson Andrén ,&nbsp;Dewa Safi ,&nbsp;Anders Wallin ,&nbsp;Johan Svensson","doi":"10.1016/j.cccb.2024.100229","DOIUrl":"https://doi.org/10.1016/j.cccb.2024.100229","url":null,"abstract":"<div><h3>Background</h3><p>There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between lipid concentrations and the subsequent risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. Here, we determined whether lipid levels are associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD).</p></div><div><h3>Methods</h3><p>This was a longitudinal, prospective study of 329 patients with subjective or objective mild cognitive impairment at baseline. The statistical analyses included Cox proportional hazards regression with adjustments for age, gender, education, body mass index, current smoking, hypertension, diabetes mellitus, and <em>APOE</em> ε4 genotype.</p></div><div><h3>Results</h3><p>During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, <em>n</em> = 15 (5 %); AD, <em>n</em> = 39 (12 %); and mixed dementia, <em>n</em> = 26 (8 %)]. Serum high-density lipoprotein cholesterol (HDL, per SD increase) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with SSVD risk. Furthermore, the lowest HDL tertile was associated with a sevenfold, and the highest tertile of TG/HDL ratio with a threefold, increase in SSVD risk. There were no associations with the risk of AD or mixed dementia after adjustment for covariates.</p></div><div><h3>Conclusion</h3><p>In a memory clinic population, low HDL and high TG/HDL ratio were independent risk factors of SSVD, but not of AD or mixed dementia.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000308/pdfft?md5=9e09925c27dcfc8bbf12e57fcbec1b40&pid=1-s2.0-S2666245024000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFFECTS OF VASCULAR BURDEN ON COGNITION ARE MEDIATED BY ATROPHY, AMYLOID, AND GLUCOSE METABOLISM: A MULTI-CENTRE MIXED COHORT OF SMALL VESSEL DISEASE AND ALZHEIMER'S PATHOLOGY","authors":"Julie Ottoy LC Campbell ,&nbsp;Miracle Ozzoude LC Campbell ,&nbsp;Katherine Zukotynski LC Campbell ,&nbsp;Sabrina Adamo LC Campbell ,&nbsp;Christopher Scott LC Campbell ,&nbsp;Vincent Gaudet ,&nbsp;Joel Ramirez LC Campbell ,&nbsp;Walter Swardfager ,&nbsp;Hugo Cogo-Moreira LC Campbell ,&nbsp;Benjamin Lam LC Campbell ,&nbsp;Aparna Bhan LC Campbell ,&nbsp;Parisa Mojiri LC Campbell ,&nbsp;Min Su Kang ,&nbsp;Jennifer Rabin LC Campbell ,&nbsp;Alex Kiss ,&nbsp;Stephen Strother ,&nbsp;Christian Bocti ,&nbsp;Michael Borrie ,&nbsp;Howard Chertkow ,&nbsp;Richard Frayne ,&nbsp;Maged Goubran LC Campbell","doi":"10.1016/j.cccb.2022.100105","DOIUrl":"https://doi.org/10.1016/j.cccb.2022.100105","url":null,"abstract":"","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100105"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245022000708/pdfft?md5=dcedbfc8ec5ab4c82cde2be537498759&pid=1-s2.0-S2666245022000708-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141480272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RELATIONSHIP BETWEEN CEREBROVASCULAR PATHOLOGY AND RESTING-STATE FUNCTIONAL CONNECTIVITY: A SYSTEMATIC REVIEW","authors":"Natasha Clarke ,&nbsp;Désirée Lussier ,&nbsp;Flavie Detcheverry ,&nbsp;Eric Smith ,&nbsp;Sridar Narayanan ,&nbsp;AmanPreet Badhwar","doi":"10.1016/j.cccb.2022.100055","DOIUrl":"https://doi.org/10.1016/j.cccb.2022.100055","url":null,"abstract":"","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100055"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245022000204/pdfft?md5=4c44052ef85d5e09b21d492903229562&pid=1-s2.0-S2666245022000204-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VISIT-TO-VISIT VARIABILITY IN BLOOD PRESSURE OVER 10 YEARS, COGNITIVE DECLINE AND INCIDENT DEMENTIA IN THREE COMMUNITY-BASED COHORTS OF OLDER ADULTS","authors":"Simin Mahinrad,&nbsp;Lisa Barnes,&nbsp;David Bennett,&nbsp;Farzaneh Sorond,&nbsp;Philip Gorelick","doi":"10.1016/j.cccb.2022.100086","DOIUrl":"https://doi.org/10.1016/j.cccb.2022.100086","url":null,"abstract":"","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100086"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245022000514/pdfft?md5=82bfb71e5077c17229b14398f00c67b0&pid=1-s2.0-S2666245022000514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141482075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using routinely acquired electronic patients records (EPRs) and brain imaging to study novel risk factors for vascular dementia in older hospital patients","authors":"Emma Colbourne ,&nbsp;Emily Boucher ,&nbsp;Taylor Hanayik ,&nbsp;Katerina Wartolowska ,&nbsp;Sarah T Pendlebury","doi":"10.1016/j.cccb.2024.100323","DOIUrl":"10.1016/j.cccb.2024.100323","url":null,"abstract":"<div><h3>Introduction</h3><p>Delirium and infection are risk factors for dementia, with infection more strongly linked to vascular than Alzheimer's-type dementia. It is unclear whether regional atrophy and white matter changes (WMC) of vascular origin modify these relationships. To inform future studies, we determined rates of cognitive frailty and frequency of brain scans in consecutive older hospital in-patients using routinely acquired electronic patient records (EPRs) data.</p></div><div><h3>Methods</h3><p>The Oxford Cognitive Comorbidity and Ageing Research Database (ORCHARD) includes real-world EPR data from consecutive older patients admitted to four general hospitals in Oxfordshire, UK (n=660,000 population). ORCHARD includes detailed data on cognitive frailty (dementia history, delirium diagnosis using the Confusion Assessment Method-CAM and 10-point Abbreviated-Mental-Test Score, AMTS), comorbidities, nutrition, falls risk, frailty, clinical observations, laboratory tests, and routine brain imaging. Long-term dementia outcomes are obtained from electronic records linkage including to regional mental health databases. Atrophy is rated using the Global Cortical Atrophy scale (GCA) and WMC using the Age-Related WMC (ARWMC) scale.</p></div><div><h3>Results</h3><p>Between 2017 and 2019, there were 51,202 consecutive unplanned admissions (adults &gt;70 years with &gt;1 unplanned admission lasting &gt;1 day). The mean/SD age of patients was 82/7 years. Cognitive frailty was present in 17,466 (34.5%, 95%CI 34.0-34.9%) overall: delirium=7,411 (14.6%), delirium+dementia=4,757 (9.4%), dementia=3,784 (7.5%), AMTS&lt;8=1,514 (3%). In a subset of 1100 consecutive patients, 668 patients had available brain imaging (CT: 96%, MRI: 22%, both: 18%). On the rated CT scans (n=290 for atrophy, n=117 for WMC), global atrophy was mild in 12%, moderate in 71%, and severe in 17%; temporal lobe atrophy was absent in 1%, mild in 49%, moderate in 46%, and severe in 4%; WMC was mild in 58%, moderate in 38%, and severe in 3%.</p></div><div><h3>Discussion</h3><p>Cognitive frailty, particularly delirium without dementia, was prevalent in older patients with unplanned hospital admission. Over half of older patients had brain imaging available with high rates of moderate/severe atrophy and WMC. These findings suggest that routinely acquired EPR can be combined with available brain imaging to explore (vascular) dementia risk factors such as delirium and infection in hospital “Big Data” studies.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100323"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001247/pdfft?md5=15e71ec47de872321451ddf788569e20&pid=1-s2.0-S2666245024001247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo imaging of gadolinium-based contrast agent leakage in patients with cerebral amyloid angiopathy","authors":"Hilde van den Brink ,&nbsp;Mariel G Kozberg ,&nbsp;Nazanin Makkinejad ,&nbsp;John Kirsch ,&nbsp;Whitney M Freeze ,&nbsp;Anand Viswanathan ,&nbsp;Susanne J van Veluw","doi":"10.1016/j.cccb.2024.100324","DOIUrl":"10.1016/j.cccb.2024.100324","url":null,"abstract":"<div><h3>Introduction</h3><p>Blood-brain barrier (BBB) leakage is hypothesized to be an early step in the pathophysiology of cerebral amyloid angiopathy (CAA), possibly preceding vessel wall breakdown and hemorrhage. This study aims (1) to measure BBB leakage in vivo in the parenchyma and at the level of the leptomeningeal blood vessels in patients with CAA without lobar intracerebral hemorrhage compared to controls and (2) to study the relationship between BBB leakage and neuroimaging markers of CAA severity.</p></div><div><h3>Methods</h3><p>To date, 13 participants with probable CAA without prior intracerebral hemorrhage (age 67±9 years, 8 females) and 5 non-CAA controls with mild cognitive impairment (CDR 0.5 or 1) and no microbleeds (age 70±7 years, 1 female) have been included into the study. The 3T MRI protocol included pre- and post-contrast T1-weighted (0.9 × 0.9 × 0.9 mm3) and T2-FLAIR scans (0.9 × 0.9 × 0.9 mm3, TE 500 ms), an SWI (0.6 × 0.6 × 1.4 mm3), and a Dynamic Contrast Enhanced (DCE) scan (0.9 × 0.9 × 3.0 mm3). Participants received (0.2mL/kg) a gadolinium-based contrast agent (Dotarem) intravenously during the DCE scan. DCE scans were analyzed with ROCKETSHIP software to quantify the permeability-surface area product (PS), which represents the rate at which contrast agent leaks from the plasma into the parenchyma. Leptomeningeal CSF enhancement is measured by visually inspecting post-contrast versus pre-contrast T2-FLAIR scans.</p></div><div><h3>Preliminary Results</h3><p>Preliminary analysis revealed higher whole-brain PS in participants with CAA compared to non-CAA controls (Figure 1). Figure 2 shows an example of leptomeningeal CSF enhancement on post-contrast T2-FLAIR (2b) versus pre-contrast T2-FLAIR (2a). Ongoing analyses will compare PS-values in the cortex and white matter and in the occipital and frontal lobe. Furthermore, we aim to study the relationship between parenchymal and leptomeningeal contrast leakage with hemorrhagic neuroimaging markers (i.e. cortical microbleeds and cortical superficial siderosis) on SWI.</p></div><div><h3>Discussion</h3><p>These preliminary results indicate that we can capture BBB leakage in vivo in our cohort, and that parenchymal BBB leakage is higher in patients with CAA compared to controls. Successful completion of this ongoing study will aid our understanding of the role of BBB leakage in the pathophysiology of CAA and the potential added value of BBB imaging as an early disease biomarker in CAA.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100324"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001259/pdfft?md5=69e0e2ce93e918505a3db76e340c6674&pid=1-s2.0-S2666245024001259-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac functional and structural impairments, endothelial apoptosis and blood-brain barrier dysfunction in models of cerebrovascular amyloidosis in the presence or absence of hyperhomocysteinemia","authors":"Ashley Carey,&nbsp;Andrea Elia,&nbsp;Rebecca Parodi-Rullan,&nbsp;Silvia Fossati","doi":"10.1016/j.cccb.2024.100239","DOIUrl":"10.1016/j.cccb.2024.100239","url":null,"abstract":"<div><p>Cerebrovascular dysfunction has been implicated as a major early contributor to Alzheimer's Disease (AD) pathology, with endothelial cell (EC) stress resulting in focal ischemia, cerebral blood flow impairments, and blood brain barrier (BBB) permeability. Recent evidence suggests that cardiovascular (CV)/cerebrovascular risk factors, such as hyperhomocysteinemia (Hhcy) contribute to increasing AD pathology and risk, but it remains unknown whether Amyloid beta (Aβ) and homocysteine function through common molecular mechanisms to induce EC dysfunction. Additionally, Aβ is known to mediate degeneration of the brain neuro-signaling pathways. Neurotrophic factors depletion, together with vascular and peripheral amyloid accumulation, may also result in the derangement of the peripheral nervous system, culminating in detrimental effects on other organs, including the heart. However, whether and how AD pathology modulates cardiac function, cardiac amyloidosis and heart innervation is still unknown. Here, we will discuss two important and new mechanistic perspectives on the vascular contributions to cognitive impairment and dementia:</p><p>Our new mechanistic data demonstrates that Hhcy specifically potentiates Aβ-mediated activation of the death receptors 4/5 (DR4/5)-mediated extrinsic apoptotic pathway in cerebral ECs. Additionally, we revealed that Hhcy potentiates Aβ-mediated EC barrier permeability, deregulating specific junction proteins expression, localization, and phosphorylation. Moreover, Hhcy and Aβ impair VEGF-A and VEGFR2 signaling and VEGFR2 endosomal trafficking, additively decreasing EC angiogenic capabilities. This work highlights new potential molecular targets against cerebrovascular pathology in comorbid AD/CAA and Hhcy conditions.</p><p>We will describe the first report of cardiac remodeling, amyloid deposition, and neuro-signaling dysregulation in the heart of Tg2576 mice, a widely used model of AD and cerebral amyloidosis. Tg2576 mice hearts exhibited an accumulation of amyloid aggregates, including Aβ40, together with a robust reduction in NGF and BDNF protein expression, leading to interstitial fibrosis and severe cardiac nervous system dysfunction. The transgenic mice also showed a significant decrease in cardiac adrenergic and regenerating nerve endings. Our data suggest that AD amyloid pathology can cause deleterious functional effects on the heart, and the peripheral neurotrophic pathway may represent a potential therapeutic target to limit these effects.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100239"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000400/pdfft?md5=2f0f940e30088fb6d3e423a236702ba2&pid=1-s2.0-S2666245024000400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of white matter hyperintensity regression on global cognition, processing speed and executive function","authors":"Angela Jochems ,&nbsp;Susana Muñoz Maniega ,&nbsp;Una Clancy ,&nbsp;Daniela Jaime Garcia ,&nbsp;Carmen Arteaga ,&nbsp;Mariadel C. Valdés Hernández ,&nbsp;Will Hewins ,&nbsp;Rachel Penman ,&nbsp;Ellen Backhouse ,&nbsp;Stewart Wiseman ,&nbsp;Michael Thrippleton ,&nbsp;Michael Stringer ,&nbsp;Francesca Chappell ,&nbsp;Fergus Doubal ,&nbsp;Joanna Wardlaw","doi":"10.1016/j.cccb.2024.100243","DOIUrl":"10.1016/j.cccb.2024.100243","url":null,"abstract":"<div><h3>Introduction</h3><p>White matter hyperintensities (WMH) are related to cognitive decline, particularly processing speed and executive functioning (EF). However, all cognitive domains might be affected. WMH can regress and this might have positive consequences for cognition, but the effects of WMH regression on cognition are unknown. This study aims to assess whether changes in global cognition, processing speed and EF are related to progressing and regressing WMH.</p></div><div><h3>Methods</h3><p>We recruited mild, non-disabling, ischemic stroke patients with sporadic small vessel disease. They underwent MRI and cognitive assessment within 3 months post-stroke and 1 year later. Cognitive assessment included MoCA (global cognition; score 0-30), trail making test (TMT) A (processing speed; seconds) and TMT B (EF; seconds). WMH volumes are reported as % intracranial volume (ICV). WMH volume change (%ICV) is defined as WMH volume difference between baseline and 1 year. We calculated quintiles (Q) of WMH volume change to group volume change. We performed three linear mixed models, with MoCA, TMT-A and B as outcomes, to assess relationships over time with quintile of WMH volume change. Predictors in addition to quintile are age, sex, premorbid intelligence (NART), stroke severity (NIHSS). Extra predictor for TMT-B analysis is the TMT-A time to correct for speed.</p></div><div><h3>Results</h3><p>202 participants had WMH change volumes available (mean age: 66.03 years [SD=11.15), 33% female]. Q1 reflect greatest WMH volume reduction and Q5 greatest volume increase, while Q3 is lowest overall volume change (Figure 1). MoCA score increased over time (Figure 2). Older age (std. B [std. 95%CI]: -0.303 [-0.400, -0.206]), worse NART (-0.463 [-0.557, -0.368]), increasing NIHSS (-0.208 [-0.286, -0.130]) and more WMH increase (Q5; -0.513 [-0.814, -0.211]) predict lower MoCA. Older age (0.257 [0.135, 0.380]), worse NART (0.259 [0.139, 0.378]) and higher NIHSS (0.152 [0.078, 0.226]) predict worse TMT-A time (Figure 3A). Older age (0.224 [0.132, 0.316]), worse NART (0.295 [0.207, 0.383]), worse TMT-A (0.469 [0.384, 0.555]), worsening WMH volume (Q2; 0.382 [0.115, 0.0.649] and Q5; 0.425 [0.150, 0.699]) predict worse TMT-B time (Figure 3B).</p></div><div><h3>Discussion</h3><p>More WMH progression independently predicts worse global cognition and EF but not processing speed. WMH regression (Q1) was not related to worsening or improving global cognition, processing speed and EF. Cognitive consequences of WMH regression might be comparable to stable WMH (Q3).</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100243"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000448/pdfft?md5=1278f4870900323bf0a34ac521701724&pid=1-s2.0-S2666245024000448-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}