Cerebral circulation - cognition and behavior最新文献

{"title":"Morphometric Features of Brain Perivascular Spaces and Their Neuropsychiatric and Familial Associations","authors":"Alexandra Morozova ,&nbsp;Maria del C. Valdés Hernández ,&nbsp;Roberto Duarte Coello ,&nbsp;Heather Whalley ,&nbsp;Andrew McIntosh ,&nbsp;Anca-Larisa Sandu Giuraniuc ,&nbsp;Gordon D. Waiter ,&nbsp;Christopher J McNeil ,&nbsp;Douglas Steele ,&nbsp;Joanna M. Wardlaw","doi":"10.1016/j.cccb.2025.100419","DOIUrl":"10.1016/j.cccb.2025.100419","url":null,"abstract":"<div><h3>Introduction</h3><div>Stress, depressive symptoms, cardiovascular health, and physical strength are well-recognised factors contributing to microcirculatory changes in the brain, accentuating the multifactorial nature of these alterations. MRI-detectable brain perivascular spaces (PVS) have been proposed as neuroimaging markers reflecting microcirculatory dynamics. However, it remains unclear whether perivascular morphology is affected by these neuropsychiatric and physiological determinants, and which specific morphometric features are influenced by familial factors beyond established overall genetic contributions. Therefore, our study aims to investigate the associations between neuropsychiatric factors – hair cortisol, Quick Inventory of Depressive Symptomatology scale score, and hand grip strength – and PVS characteristics in a healthy aging population. In addition, it seeks to investigate the potential influence of familial factors on PVS characteristics through first-degree relatives.</div></div><div><h3>Methods</h3><div>We used the Stratifying Depression and Resilience Longitudinally (STRADL) family-based cohort to assess the association between these factors, familial influences, and PVS characteristics. Using an automated segmentation method on brain magnetic resonance images, we generated perivascular space volume, count, density (i.e., count per unit volume), and median length in the centrum semiovale (CSO) and the basal ganglia (BG) of 1183 participants, including 324 subjects with first-degree relatives within the cohort. The statistical analyses were conducted using Linear Mixed Effects Models built for each PVS measurement.</div></div><div><h3>Results</h3><div>Significant associations were identified between increasing PVS burden, advancing age and current depressive symptoms in both the BG and the CSO regions. Increased PVS burden in the CSO was associated with higher hair cortisol and weaker hand grip strength. Familial factors were significant in determining PVS volume and median length in the CSO, with age being a substantial contributor.</div></div><div><h3>Conclusions</h3><div>Chronic stress exposure and physical strength are reflected in the PVS morphology of the CSO, whereas depressive symptomatology affects both the BG and the CSO regions. Familial effects on CSO PVS volume and length were observed, contributing to our understanding of potential genetic and environmental influences on PVS morphology.</div><div>The regional variability in PVS burden provides insights into differences in the pathophysiology of perivascular clearance across brain regions, suggesting that specific changes in PVS characteristics may depend on the nature of influencing factors.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100419"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The VASCOG-2-NP consensus harmonized neuropsychological assessment for Vascular Cognitive Impairment and Dementia: Introduction, validation and future directions","authors":"The VASCOG-2-NP Consortium","doi":"10.1016/j.cccb.2025.100468","DOIUrl":"10.1016/j.cccb.2025.100468","url":null,"abstract":"<div><h3>Introduction</h3><div>Harmonization of neuropsychological assessment for vascular cognitive impairment and dementia (VCID) is important for ensuring the highest standards and consistency of diagnosis. A battery proposed in 2006 by the National Institute for Neurological Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN) has received much international support. Considering significant developments in the understanding of small vessel disease and its neuropsychological correlates in VCID, plus a recent increase in remote and computerized assessment methods, an international expert group was established to update this battery and add guidelines.</div></div><div><h3>Methods</h3><div>Forty-four international experts in neuropsychological assessment from diverse regions were invited to participate. An online Delphi survey (minimum three rounds, ≥ 75% threshold for agreement) was used to achieve consensus on a core test battery based on key cognitive domains that should be assessed for VCID, that is adaptable for telehealth and computerized assessment methods, and for assessment of diverse populations.</div><div>Reference points were NINDS-CSN and other relevant published harmonized neuropsychological batteries, aided by literature review of recent developments in VCID.</div></div><div><h3>Results</h3><div>Three survey rounds included 28-31 participants that agreed on a “Core” assessment battery of neuropsychological tests based on key cognitive domains, and additional guidelines for a more comprehensive test battery, cognitive screening, telehealth and computerized assessment methods, principles for normative standardisation, and the assessment of diverse populations. The key cognitive domains were harmonized with the VASCOG-2-WSO diagnostic criteria for VCID.</div></div><div><h3>Conclusions</h3><div>The harmonized neuropsychological assessment battery and guidelines for VCID (VASCOG-2-NP) expand upon the NINDS-CSN battery with more comprehensive and flexible assessment of VCID. Harmonized with the VASCOG-2-WSO diagnostic criteria, VASCOG-2-NP could be adopted internationally to further help more consistent neuropsychological evaluations related to VCID. We will compare the VASCOG-2-NP to the NINDS-CSN and other previous batteries for VCID, and discuss future research directions including validation against neuropathological diagnosis of small vessel disease.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100468"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enlarged Perivascular Spaces changes during the day in Healthy Volunteers","authors":"Roberto Duarte Coello ,&nbsp;Maria del C. Valdés Hernández ,&nbsp;Nina M Rzechorzek ,&nbsp;Michael Thrippleton ,&nbsp;Joanna M. Wardlaw","doi":"10.1016/j.cccb.2025.100422","DOIUrl":"10.1016/j.cccb.2025.100422","url":null,"abstract":"<div><h3>Introduction</h3><div>Perivascular spaces (PVS) in the brain are fluid-filled structures which, when enlarged, become visible on MRI scans. They are believed to play a role in clearing brain fluids. However, daily variations in the size of enlarged PVS have not been thoroughly investigated. If such variations are significant, it may be important to standardise the time of image acquisition or adjust for these changes in PVS analyses.</div></div><div><h3>Methods</h3><div>We used MRI scans from the Circadian Brain Temperature Study (CiBraT), which consists of healthy volunteers scanned three times in a single day: 9am, 4pm and 11pm.</div><div>For this analysis, we included only participants who completed all three scans (N=38). The Basal Ganglia and the Centrum Semiovale regions were analysed. We normalised the T1- and T2-weighted input images. PVS were segmented by thresholding the output of the vesselness filter. We removed outliers based on volume and contrast. We also tested a refinement step based on image intensity for each PVS. We measure: total PVS volume and count, and the mean length, diameter, and volume of individual PVS using a curve approximation (Bezier). Repeated-measures (RM) ANOVA was used to assess whether these measurements varied significantly throughout the day. Analyses were performed separately for T1- and T2-weighted images, using both Frangi and RORPO filters, and with or without the refinement step.</div></div><div><h3>Results</h3><div>There were no significant differences in any of the PVS measurements across T1- and T2-weighted scans, for the RORPO filter or whether PVS refinement was applied or not. However, refining the PVS segmentation improved the measurement consistency for both filters. RM-ANOVA showed potential differences for some of the Frangi measurements. We noted visually that longer PVS structures were fragmented, which led to an increased count and a decrease in mean individual length and size between scans, which could explain these results.</div></div><div><h3>Conclusions</h3><div>Our results suggest that PVS volume, count, and morphology in healthy volunteers do not change significantly over the course of the day in brain MRI. Post- processing of PVS segmentations can improve the consistency of these measurements. In terms of morphology and count, the RORPO filter provides more consistent results than the Frangi filter.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100422"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of ryanodine receptor to BK channel nanodomains in cerebral arteries may underlie hypertension-associated cognitive decline","authors":"Harry Pritchard ,&nbsp;Anna Gray ,&nbsp;Adam Greenstein ,&nbsp;Stuart Allan ,&nbsp;Ingo Schiessl ,&nbsp;Alexander Clowsley ,&nbsp;Christian Soeller ,&nbsp;Thea Danby","doi":"10.1016/j.cccb.2025.100498","DOIUrl":"10.1016/j.cccb.2025.100498","url":null,"abstract":"<div><h3>Introduction</h3><div>The innate ability of cerebral resistance vessels to maintain constant blood flow during fluctuations in global blood pressures is a tightly controlled process known as autoregulation. This relies on a negative feedback mechanism in vascular smooth muscle cells (SMCs) where calcium sparks released from ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) activate large-conductance calcium-activated potassium (BK) channels on the plasma membrane (PM). Efficient activation requires RyRs and BK channels to reside within ∼20nm of each other. Disruption of this nanoscale proximity impairs BK channel activation, compromising vasodilation and blood flow regulation seen during chronic hypertension.</div></div><div><h3>Methods</h3><div>To investigate RyR-BK spatial coupling, we will utilise DNA-PAINT super- resolution microscopy to image isolated SMCs from wild-type (C57), normotensive (BPN/3), and hypertensive (BPH/2) mice. Confocal microscopy will be used to quantify calcium spark activity and the number of spark sites per cell and electron microscopy (EM) will assess SR- PM contact sites at the ultrastructural level. In-vivo cerebral blood flow (CBF) will be measured using multi-photon microscopy in mice with cranial windows, with vasodilation assessed via CO₂ challenge.</div></div><div><h3>Results</h3><div>In C57 mice, DNA-PAINT revealed that ∼40% of RyRs were located within 30nm of BK channels, with ∼90% within 100nm, suggesting tight spatial organisation. Calcium imaging showed an average of ∼2 calcium spark sites per isolated SMC, indicating a limited number of functional coupling sites where preliminary EM findings confirmed sparse SR-PM coupling in healthy SMCs. These findings establish a baseline for functional RyR-BK coupling in health. In our previous work (Taylor et al., 2023), BPH/2 mice showed reduced CBF, impaired BK channel activity, and significantly fewer RyR-BK coupling sites compared to BPN/3 controls, indicating a spatial uncoupling during chronic hypertension. Current experiments are extending these analyses in BPH/2 mice using the same imaging modalities to further assess nanoscale changes and functional modifications.</div></div><div><h3>Conclusions</h3><div>These results suggest RyR-BK coupling is sparse and spatially precise in healthy SMCs, with nanoscale organisation being essential for proper arterial diameter control. Chronic hypertension disrupts this arrangement contributing to impaired autoregulation. Understanding when and how this coupling is lost could help identify new therapeutic strategies to restore cerebrovascular function and prevent cognitive decline.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100498"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White Matter Brain Age Gap Independently Mediates Vascular Risk and Cognitive Decline Beyond Grey Matter Age","authors":"Zaylea Kua,&nbsp;Ruijia Tian,&nbsp;Boon Thye Thomas Yeo,&nbsp;Yanhong Dong,&nbsp;Richard Henson,&nbsp;Kamen Tsvetanov","doi":"10.1016/j.cccb.2025.100420","DOIUrl":"10.1016/j.cccb.2025.100420","url":null,"abstract":"<div><h3>Introduction</h3><div>Brain-Age Gap (BAG), which quantifies deviations between an individual’s predicted brain age and chronological age, has emerged as a novel tool for investigating risk factors on brain health. White matter and cognitive decline are affected by vascular risk factors (VRFs), but it is unclear to what extent white matter (WM) disruptions contribute independently of gray matter (GM) differences. This study hypothesized that the effect of VRFs on cognitive abilities in healthy adults would be mediated by WM-BAG, potentially independently of GM-BAG.</div></div><div><h3>Methods</h3><div>This cross-sectional study was based on the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) lifespan healthy adult cohort (age 18-88 years). WM-BAG was estimated from 8 diffusion metrics x 48 ROIs using a Least Absolute Shrinkage and Selection Operator regression model while GM-BAG was estimated from 4 morphometric measures x 148 ROIs using an Elastic Net regression model; both were bias-corrected. VRF status (binary) was defined by presence of ≥1: current smoking, hypertension, hyperlipidemia, or BMI ≥ 30 kg/m². Cognitive outcomes were processing speed from a speeded key-press task, and fluid intelligence from the Cattell test. Mediation analysis of the direct VRF-&gt;Cognition path by an indirect path via WM-BAG was estimated using Python (pingouin v0.5.3), after controlling for age, sex, years of education and GM-BAG.</div></div><div><h3>Results</h3><div>Of 503 participants in the final analytical sample, 38.4% were VRF-positive. Presence of VRF predicted higher WM-BAG (β = 1.29, SE = 0.55, p = 0.019). Following adjustment of age, sex, and education, WM-BAG fully mediated the association between VRF and processing speed (23.0% mediation proportion, p = 0.013) while a suppression effect was observed for fluid intelligence (p = 0.008); see Figure 1. Following additional adjustment for GM-BAG, the indirect effect remained significant for fluid intelligence (p = 0.039), though that for processing speed was attenuated. Sex‐stratified analyses revealed that WM-mediated vascular effects on cognition were more pronounced in females than in males.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that behaviorally relevant white matter disruption, captured by WM-BAG, is especially sensitive to vascular risk and may serve as an early biomarker of cerebrovascular contributions to cognitive decline, with potential sex-specific vulnerabilities that warrant targeted intervention.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100420"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of pacemaker implantation on the risk of vascular cognitive decline","authors":"Francesco Gill,&nbsp;Dexter Penn,&nbsp;Oliver Warrington,&nbsp;Alastair Webb","doi":"10.1016/j.cccb.2025.100414","DOIUrl":"10.1016/j.cccb.2025.100414","url":null,"abstract":"<div><h3>Introduction</h3><div>Cerebral hypoperfusion and increased pulsatility are associated with cerebral small vessel disease and vascular dementia (VaD). However, our systematic review identified no studies assessing the effects of pacemaker settings on these parameters or the risk of VaD after pacemaker implantation. We therefore determined dementia risk in people undergoing pacemaker implantation in the large UK Biobank cohort.</div></div><div><h3>Methods</h3><div>In &gt;500,000 participants in the UK Biobank cohort, we determined the absolute incidence of all-cause dementia and VaD in participants with pacemakers at recruitment or undergoing pacemaker implantation during follow-up, stratified by age and gender. To account for baseline age differences, an age and sex matched control group were derived for each individual receiving a pacemaker during follow-up (5:1 case - control ratio).</div><div>Predictors of pacemaker implantation were determined by binomial logistic regression. Dementia risk was determined by Kaplan – Meier curves and Cox’ s proportional hazards, unadjusted and adjusted for cardiovascular risk factors and predictors of pacemaker implantation including HF and MI.</div></div><div><h3>Results</h3><div>Of 502,128 participants (median follow-up= 13.6 years), 11,811 had pacemakers, with a mean age of 62 years. Absolute incidence of all-cause dementia was greatest in 10, 258 people after pacemaker implantation during the study (654/100,000 person years), then in people with pacemakers at baseline (448/100,000 person years) and lowest in non- paced people (141/100,000 person years, p&lt;0.0001), with similar differences for VaD (249 vs 154 vs 30 /100,000 person years, p&lt;0.0001). Compared to those that were never paced, all-cause dementia risk was significantly higher in people paced at baseline (HR= 3.42, 2.76 - 4.24 95%CI, p= &lt;0.05), or after pacemaker implantation in the age and sex- matched dataset (HR = 1.47, 1.30 - 1.67 95% CI), even after adjustment (baseline HR = 1.32; during HR= 1.37), with consistent effects for VaD (adjusted: baseline HR= 1.77; during HR= 1.38).</div></div><div><h3>Conclusions</h3><div>In the UKB, participants with pacemakers had a high risk of dementia, identifying a key target for future interventions. Future studies should investigate how to optimise pacemaker settings to improve cerebral haemodynamics, and whether this reduces the subsequent risk of cognitive decline.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100414"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin resistance increases the risk of incident Subcortical Small Vessel Type of Dementia","authors":"Elin Axelsson Andrén ,&nbsp;Petronella Kettunen ,&nbsp;Anders Wallin ,&nbsp;Johan Svensson","doi":"10.1016/j.cccb.2025.100440","DOIUrl":"10.1016/j.cccb.2025.100440","url":null,"abstract":"<div><h3>Introduction</h3><div>Insulin resistance (IR) has been associated with cognitive decline and cortical vascular cognitive impairment. While IR has been linked to white matter abnormalities in population-based studies, few studies have examined the impact of IR in a clinical population.</div><div>The aim was to investigate the association between baseline Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the risk of progression to the subcortical small vessel type of dementia (SSVD) or Alzheimer's disease (AD) in a memory clinic cohort.</div></div><div><h3>Methods</h3><div>A total of 352 patients with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI) were followed for up to six years (mean follow-up: 4.1 years). Cox proportional hazards regression models were used to assess the association between baseline HOMA-IR and the risk of SSVD or AD with adjustment for relevant covariates.</div></div><div><h3>Results</h3><div>During the follow-up, 24% (n=83) of the SCI/MCI patients converted to dementia (SSVD, n = 28; AD, n = 55). Higher HOMA-IR levels were significantly associated with increased risk of progression to SSVD (adjusted hazard ratio [HR] = 1.42, 95% CI: 1.17–1.73, p &lt; 0.001), but not with the risk of AD. Patients in the highest HOMA-IR quintile (Q5) had a markedly elevated risk of SSVD compared to those in the lowest quintile, Q1 (adjusted HR = 6.60, 95% CI: 1.02 – 42.54, p &lt; 0.05). No significant association was observed between HOMA-IR and the risk of AD.</div></div><div><h3>Conclusions</h3><div>Insulin resistance is an independent predictor of conversion to SSVD, but not of the risk of AD, among patients with SCI or MCI. These findings highlight the potential role of metabolic dysfunction in the pathogenesis of SSVD and suggest that HOMA-IR could be useful both in the identification and prevention of progression to SSVD in a memory clinic population.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100440"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Psychological Tests in Non-demented Japanese CADASIL Patients","authors":"Satoshi Saito,&nbsp;Chikage Kakuta,&nbsp;Hiroyuki Ishiyama,&nbsp;Tomotaka Tanaka,&nbsp;Masafumi Ihara","doi":"10.1016/j.cccb.2025.100459","DOIUrl":"10.1016/j.cccb.2025.100459","url":null,"abstract":"<div><h3>Introduction</h3><div>Previous studies have reported the usefulness of the Montreal Cognitive Assessment (MoCA) and other psychological tests, primarily in Caucasian patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In this study, we evaluated the effectiveness of psychological tests in detecting mild cognitive impairment in Japanese patients with CADASIL, including those with the pro-hemorrhagic subtype associated with the NOTCH3 p.R75P variant.</div></div><div><h3>Methods</h3><div>In this single-center prospective study, we examined the utility of the MoCA, Mini-Mental State Examination (MMSE), Trail Making Test (TMT), and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Dementia patients (Clinical dementia rating [CDR]≧1) were excluded. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of mild cognitive impairment (CDR=0.5).</div></div><div><h3>Results</h3><div>Out of the 61 CADASIL patients who gave written informed consent and visited our clinic between January and December 2022, 51 were included in this study, and 10 were excluded due to CDR≧1. The mean age (standard deviation) was 54 (8), and 28 (55%) were male. The most common mutation was the p.R75P variant, found in 11 patients (22%). Based on the CDR scores, we classified the 51 CADASIL patients into 19 with mild cognitive impairment and 32 without. The ROC analysis showed an area under the curve of 0.90 for MoCA, 0.72 for MMSE, 0.81 and 0.86 for TMT-A and B, and 0.77 and 0.73 for WAIS- IV Digit Span and Digit Symbol. The optimal cut-off values for MMSE and MoCA were 27/28 (sensitivity, 0.58; specificity, 0.84) and 24/25 (sensitivity, 0.74; specificity, 0.97), respectively.</div></div><div><h3>Conclusions</h3><div>The MoCA and TMT were found to be sensitive screening tools for detecting mild cognitive impairment in Japanese patients with CADASIL.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100459"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased levels of Chitinase-3-like protein 1 in blood is associated with increased Matrix Metaloproteinase-10 and reduced cognition in an amnestic MCI cohort","authors":"Jiaqi Liu ,&nbsp;Sofia Michopoulou ,&nbsp;Jessica L. Teeling","doi":"10.1016/j.cccb.2025.100410","DOIUrl":"10.1016/j.cccb.2025.100410","url":null,"abstract":"<div><h3>Introduction</h3><div>Altered blood-brain barrier (BBB) function can influence Alzheimer’s Disease (AD) progression. Chitinase-3-like protein 1 (Chi3l1/YKL-40) has been suggested as a potential AD fluid biomarker to predict disease progression and is increased in CSF/blood from patients diagnosed with MCI and AD. In AD, Matrix Metaloproteinase-10 (MMP-10) levels in the cerebrospinal fluid (CSF) are also increased in AD compared to healthy controls, with higher level being related to more vulnerable BBB. The sampling of CSF is invasive, and blood samples can be more widely used. Compared with CSF, there are relatively limited studies focus on AD diagnostic potential of YKL-40 and MMP-10 in serum. Here we evaluate if levels of YKL-40 and MMP-10 in blood samples is associated with cognitive decline in a human dementia cohort.</div></div><div><h3>Methods</h3><div>Serum samples from 102 participants, including 44 healthy controls and 58 patients with amnestic mild cognitive impairment (aMCI) in the ICOS study were analysed (Sussams et al., 2020). Participants were monitored for cognitive function (MoCA) at six- monthly intervals over 18 months and a follow up at 5 years. Blood samples obtained at 12 months post recruitment were analysed in this study. The levels of MMP-10 and YKL-40 were measured using Mesoscale platform. Correlation analysis was used to evaluate if these markers are associated with cognitive function. For comparison, brain sections from 11 months old wild-type mice and APP/PS1 transgenic mice were analysed for expression levels of YKL-40 in association with the cerebral vasculature (CD31).</div></div><div><h3>Results</h3><div>YKL-40 showed a significant correlation between decreasing MoCA cognitive test scores (Rho=-0.319, p=0.004) and increasing concentration of MMP-10 (Rho=0.325, p=0.004). MMP-10 showed a weak but statistically significant increase with decreasing MoCA scores (Rho=-0.211, p=0.036). Immunofluorescence staining showed co-localization of YKL-40 and CD31 in both WT and APP/PS1 mouse brain.</div></div><div><h3>Conclusions</h3><div>In this study, blood levels of YKL-40 and MMP-10 were significantly associated with cognitive impairment, they are also positively associated with each other, suggesting YKL-40 might relate to BBB integrity. Mouse study confirmed the YKL-40 expression in association with endothelial cells, evidenced by the colocalization of YKL-40 with endothelial cell marker CD31. The relationship between YKL-40 and BBB integrity requires further research.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100410"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Experience from the RADAR study","authors":"Lina Jarutyte ,&nbsp;Jan Petr ,&nbsp;Nicholas Turner ,&nbsp;Patrick G. Kehoe ,&nbsp;Henk-Jan Mutsaerts ,&nbsp;David L. Thomas","doi":"10.1016/j.cccb.2024.100376","DOIUrl":"10.1016/j.cccb.2024.100376","url":null,"abstract":"<div><div>Arterial spin labelling (ASL) enables non-invasive quantification of regional brain perfusion using MRI. ASL was used in the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) multi-centre trial to pilot the assessment of the effects of the anti-hypertension drug losartan on cerebral blood flow (CBF). In the multi-centre setting, disparities in ASL implementation on scanners from different manufacturers lead to inherent differences in measured CBF and its associated parameters (e.g. spatial coefficient of variation (sCoV) of CBF, a proxy of arterial arrival times). In addition, differences in ASL acquisition parameter settings can also affect the measured quantitative perfusion values. In this study, we used data from the RADAR cohort as a case study to evaluate the site-dependent systematic differences of CBF and sCoV, and show that variations in the readout module (2D or 3D) and the post-labelling delay acquisition parameter introduced artifactual group differences. When accounting for this effect in data analysis, we show that it is still possible to combine ASL data across sites to observe the expected relationships between grey matter CBF and cognitive scores. In summary, ASL can provide useful information relating to CBF difference in multi-centre therapeutic trials, but care must be taken in data analysis to account for the inevitable inter-site differences in scanner type and acquisition protocol.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100376"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061234","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}