Cerebral circulation - cognition and behavior最新文献

{"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":"On the origin of cerebral small vessel disease: MRI markers of cSVD in young adults with hypertension","authors":"M.H. Snijders ,&nbsp;E. Janssen ,&nbsp;E. Verburgt ,&nbsp;A. ter Telgte ,&nbsp;T.N.A. van den Berg ,&nbsp;M.C. Maas ,&nbsp;F.J.A. Meijer ,&nbsp;A.M. Tuladhar ,&nbsp;N.P. Riksen ,&nbsp;J. Deinum ,&nbsp;F.E. de Leeuw","doi":"10.1016/j.cccb.2025.100397","DOIUrl":"10.1016/j.cccb.2025.100397","url":null,"abstract":"<div><h3>Introduction</h3><div>Cerebral small vessel disease (cSVD) contributes to stroke and cognitive decline, with MRI markers of cSVD increasing with age. Hypertension is an important risk factor for cSVD in older adults but its impact in younger individuals remains less clear. This study investigates whether MRI markers of cSVD are more prevalent in young hypertensive individuals compared to normotensive controls.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, 60 patients with hypertension and 21 controls aged 18–55 years underwent 3T MRI to assess cSVD markers: white matter hyperintensities (WMH), lacunes, and microbleeds. Group differences were assessed using <em>t</em>-tests, chi-square tests, or non-parametric methods. We examined associations between blood pressure and cSVD markers using multivariable regression models, including linear, logistic, ordinal logistic, and penalized logistic regression, adjusting for potential confounders.</div></div><div><h3>Results</h3><div>Patients with hypertension were older (median (IQR) 35.6 (29.6–41.4) years vs 29.2 (27.8–33.2) years), had a higher BMI, and lower education levels while proportion of females was similar. Deep WMH burden was significantly higher in hypertensive participants (median Fazekas score: 1 [IQR: 0–1] vs 0 [IQR: 0–0]; <em>p</em> &lt; 0.001). Hypertension increased odds of deep WMH (OR 5.49, <em>p</em> = 0.011). Lacunes and microbleeds were rare and observed only in hypertensive participants. Duration since hypertension diagnosis was not significantly associated with WMH volume (β=7.27, <em>p</em> = 0.111) after adjusting for age.</div></div><div><h3>Conclusion</h3><div>WMH are more prevalent in young adults with hypertension, suggesting early microvascular brain changes. These findings underscore the importance of early detection and treatment of hypertension to potentially prevent long-term cerebrovascular changes.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100397"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121180","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: Comment","authors":"Hinpetch Daungsupawong ,&nbsp;Viroj Wiwanitkit","doi":"10.1016/j.cccb.2025.100382","DOIUrl":"10.1016/j.cccb.2025.100382","url":null,"abstract":"","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100382"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696007","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":"Cerebral small vessel disease lesion segmentation methods: A systematic review","authors":"Jolene Phelps ,&nbsp;Manpreet Singh ,&nbsp;Cheryl R. McCreary ,&nbsp;Caroline Dallaire-Théroux ,&nbsp;Ryan G. Stein ,&nbsp;Zacharie Potvin-Jutras ,&nbsp;Dylan X. Guan ,&nbsp;Jeng-liang D. Wu ,&nbsp;Amelie Metz ,&nbsp;Eric E. Smith","doi":"10.1016/j.cccb.2025.100396","DOIUrl":"10.1016/j.cccb.2025.100396","url":null,"abstract":"<div><div>Cerebral small vessel disease (CSVD) can manifest as brain lesions visible on magnetic resonance imaging, including white matter hyperintensities (WMH), cerebral microbleeds (CMB), perivascular spaces (PVS), lacunes, and recent small subcortical infarcts (RSSI). Detection and segmentation of these imaging markers can provide valuable information on brain health, including prevention and treatment of dementia. However, manual segmentation is cumbersome, especially for large cohorts in research studies. There has been extensive research into the development of automated tools using machine learning to increase accuracy and efficiency in lesion segmentation. This systematic review aimed to summarize novel automated methods developed over the last 10 years that segment CSVD lesion types and have been validated on a population with or at risk for CSVD (<em>e.g.,</em> older adults, those with cognitive disorders, or those with vascular risk factors). A search on Web of Science and PubMed yielded 2764 studies, of which 89 were included after screening and full text review. 59 of these methods segmented WMH, 23 detected or classified CMB, 6 detected or segmented PVS, 5 detected, classified, or segmented lacunes, and 2 segmented RSSI. Of these, 30 studies (23 for WMH, 5 for CMB, 1 for PVS, and 1 for lacunes) included links to download code or pre-trained models, including one commercial tool, and one that relied on a commercial tool for input. Overall, this review found good evidence for high quality tools available for WMH segmentation, with fewer tools available to accurately segment other CSVD lesion types.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100396"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219507","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":"Variation in vascular risk assessment and management across UK memory/brain health clinics: a cross-sectional survey","authors":"Ross A. Dunne ,&nbsp;Lieza Exalto ,&nbsp;Simon Young ,&nbsp;Atticus Hainsworth ,&nbsp;Vanessa Raymont","doi":"10.1016/j.cccb.2025.100476","DOIUrl":"10.1016/j.cccb.2025.100476","url":null,"abstract":"<div><h3>Introduction</h3><div>Vascular risk factors (VRFs) are major, actionable contributors to cognitive dysfunction across the spectrum from vascular cognitive impairment (VCI) to mixed pathologies. Reflecting this, international and UK guidance recommend systematic identification and treatment of VRFs as part of routine care—providing clear levers for memory/brain health services to integrate risk assessment, lifestyle support and pharmacotherapy. **Objective:** To characterise current UK brain health/memory clinic practice in VRF assessment, documentation and downstream management, to inform standardisation of a pragmatic “minimum VRF dataset” and facilitate better data collection under circumstances of increased workload across health services.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional questionnaire of UK clinics routinely assessing cognition.Descriptive statistics are reported. Clinics were approached through the Dementia Platforms UK mailing list and members of the UK Brain Health Coalition were also contacted.</div></div><div><h3>Results</h3><div>Six clinics (mean 222, median 250 new referrals/year) responded to the first wave questionnaire. Overall they estimated that a mean 20.8% (range 5–50%) of referrals had pure or mixed VCI features. Five of six clinics (83%) reported routine VRF assessment for all new patients. Commonly assessed VRFs were diabetes/HbA1c, dyslipidaemia, smoking status, prior stroke/TIA, physical activity, and alcohol use (each 5/6, 83%); blood pressure, BMI/obesity, and sleep apnoea were assessed by 4/6 (67%); pulse-wave velocity and atrial fibrillation by 2/6 (33%); carotid stenosis and peripheral vascular disease by 1/6 (17%). Direct interventions provided within clinics included antihypertensives (3/6), statins (2/6), antiplatelets (2/6), and anticoagulants (1/6). VRFs were documented “always/usually” in 5/6 services. Only 2/6 reported staff training in VRF assessment within the past two years; 2/6 audited VRF assessment rates (with a further 1/6 planning to). Top barriers were time constraints (5/6), unclear guidelines (4/6), and equipment/resources (3/6). Facilitators most often cited were additional staff training (4/6), clear protocols/pathways (3/6), better IT integration (3/6), and administrative support (3/6).</div></div><div><h3>Conclusions</h3><div>UK memory / brain health clinics view VRF assessment as essential, but practice remains heterogeneous, with limited training and audit. Standardising a minimum VRF dataset and embedding clear referral/treatment pathways—supported by training, IT templates, and admin capacity—may improve consistency and impact.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100476"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796637","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":"Distinct Sodium Signatures in Vascular Dementia and Alzheimer’s Disease: A Potential Diagnostic Biomarker","authors":"Sasha Philbert ,&nbsp;Jingshu Xu ,&nbsp;Stephanie Church ,&nbsp;Richard Unwin ,&nbsp;Federico Roncaroli ,&nbsp;Garth Cooper","doi":"10.1016/j.cccb.2025.100496","DOIUrl":"10.1016/j.cccb.2025.100496","url":null,"abstract":"<div><h3>Introduction</h3><div>Vascular dementia (VaD) is the second most common cause of cognitive impairment amongst the elderly. However, there are no known disease-modifying therapies for VaD and an absence of effective clinical biomarkers that can accurately distinguish between VaD and Alzheimer’s disease (AD). A clinical marker of this nature would help future VaD clinical trials by helping ensure cohorts are comprised of VaD patients only, thus, leading to more efficient therapies. Metal dysregulation has been shown in several age-related dementias, with disease-specific patterns throughout the brain. Here, we investigated metal and protein levels in VaD to distinguish VaD from AD.</div></div><div><h3>Methods</h3><div>We employed inductively coupled plasma-mass spectrometry and liquid chromatography mass spectrometry to quantify the levels of essential metals and proteins in post-mortem VaD brain tissue (n = 10) and age-/sex-matched controls (n = 10) from seven brain regions. These data were compared with our data using the same methodology on AD patient samples. Proteomic data from the same VaD cases were used to identify possible sodium pathways.</div></div><div><h3>Results</h3><div>We observed elevated wet-weight cerebral sodium levels in VaD brain tissue in six of the seven regions analysed. Importantly, this widespread cerebral sodium elevation was not observed in AD, which instead showed a more localised elevation of sodium (3/7 brain regions, including the hippocampus, entorhinal cortex, and middle temporal gyrus). Corresponding proteomics on the same VaD tissue revealed protein expression changes, which map onto regions with elevated sodium.</div></div><div><h3>Conclusions</h3><div>These data imply widespread sodium dyshomeostasis in VaD brain tissue, which differs from AD, and may regulate – or be regulated by – specific protein expression changes. Furthermore, this cerebral sodium discrepancy between VaD and AD may have the potential as a diagnostic biomarker and help aid the clinical differentiation between VaD and AD.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100496"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796643","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":"Association of in-vivo arteriolosclerosis with Brain Age Gap and vascular risk behaviors","authors":"Anna Marseglia ,&nbsp;Caroline Dartora ,&nbsp;Eric Westman ,&nbsp;Konstantinos Arfanakis ,&nbsp;Ana W Capuano","doi":"10.1016/j.cccb.2025.100470","DOIUrl":"10.1016/j.cccb.2025.100470","url":null,"abstract":"<div><h3>Introduction</h3><div>Individuals age at different rates despite similar neuropathological burdens—some show accelerated cognitive decline, others preserve brain structure. Brain Age Gap (BAG) captures this variability in biological brain aging and has been linked to vascular risk behaviors and greater small vessel disease burden. ARTS is an in-vivo imaging marker of cerebral arteriolosclerosis, reflecting cumulative vascular risk exposure. Yet, to what extent ARTS influence BAG remains unclear. This study investigates the associations between BAG and ARTS, postmortem markers of athero-/arteriolosclerosis, vascular risk behaviors, and cognitive changes related to their interplay.</div></div><div><h3>Methods</h3><div>A total of 1,134 dementia-free individuals (mean age 79.0 ± 6.8) from four cohorts—ROS, MAP, MARS, LATC, Clinical Core of the Rush ADRC—with brain MRI were included in the study. Brain Age Gap (BAG) was computed as the difference between MRI- derived biological brain age (via deep learning) and chronological age. ARTS score was obtained from in-vivo MRI to assess arteriolosclerosis likelihood. Vascular risk behaviors (smoking, heart failure, hypertension, diabetes) were self-reported at baseline. Generalized linear models (GLM) were used, adjusting for age at MRI, sex, and education.</div></div><div><h3>Results</h3><div>Participants were 79 years of age at the MRI measure (SD=6.8), and 85% (n=966) were women. Greater ARTS score was associated with higher BAG, indicating older-appearing brains (β=2.79, SE 0.66, p&lt;0.001). BAG was associated with smoking (β = 0.71, SE = 0.26, p = 0.007) and coronary heart failure (β = 0.97, SE = 0.54, p = 0.057). When ARTS was added, the association with coronary heart failure attenuated (β = 1.13, SE = 0.59, p = 0.074), while the link with smoking remained. No interaction between ARTS and sex was observed.</div></div><div><h3>Conclusions</h3><div>ARTS is linked to older-appearing brains, potentially reflecting the lasting imprint of vascular risk exposure. Our findings support BAG as a potential imaging marker of accelerated brain aging, spotlighting the influence of often modifiable vascular risk factors in shaping brain health. The cognitive consequences of this brain-vascular aging</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100470"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796641","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":"Investigating the role of neuroinflammation and microglia on cerebrovascular function in Alzheimer's disease","authors":"Oliver Milner ,&nbsp;Robbie Fisher ,&nbsp;Daniel Asby ,&nbsp;James Armstrong ,&nbsp;Delphine Boche ,&nbsp;Scott Miners","doi":"10.1016/j.cccb.2025.100482","DOIUrl":"10.1016/j.cccb.2025.100482","url":null,"abstract":"<div><h3>Introduction</h3><div>Vessel-associated microglia (VAMs) have recently been identified as key regulators of cerebrovascular function implicated in blood-brain barrier (BBB) breakdown and impaired cerebral blood flow in Alzheimer’s disease (AD). We have explored the hypothesis that microglia migrate to the cerebral vasculature and exacerbate vascular damage associated with systemic infection and neuroinflammation.</div></div><div><h3>Methods</h3><div>We performed immunofluorescent labelling of FFPE sections from the superior temporal cortex of AD and control cases ± terminal systemic infection (N = 60). To characterise the density and phenotype of VAMs in each cohort, we immuno-labelled sections for CD31, CD68, Iba1 and HLA-DR. These measures were correlated with biochemical markers of cerebral perfusion, BBB integrity, and brain cytokine levels in corresponding frozen tissue from the same cases.</div><div>To explore microglial-cerebrovascular signalling, we exposed 3D co-cultures of HUVECs, pericytes, and microglia cultures to Aβ42 (1 uM), LPS (1 ug/mL) and Aβ42 and LPS in combination. Live cell imaging was used to assess microglial motility in response to vascular injury-conditioned media. Microarray analysis of the vascular co-culture media was conducted to identify signalling factors involved in microglial-cerebrovascular crosstalk.</div></div><div><h3>Results</h3><div>Immunofluorescence labelling showed an enrichment of Iba1+ve (p &lt; 0.05) and HLA-DR+ve (p &lt; 0.05) VAMs in AD. CD68 labelling revealed that VAMs were proportionally more phagocytic in AD alone (p &lt; 0.05) and in the presence of systemic infection (p &lt; 0.05). VAMs density was associated with markers of cerebral perfusion, BBB breakdown, and levels of brain cytokines. HMC3 microglia motility was increased upon exposure to HUVEC-pericyte media stimulated with AD-conditions. We will present data from the microarray to highlight specific signalling pathways influencing alterations in CAM motility.</div></div><div><h3>Conclusions</h3><div>We have shown that VAM density is increased in response to systemic infection and AD and is associated with neuroinflammation and markers of cerebral hypoperfusion and BBB breakdown. These studies provide further evidence that VAMs play an essential role in regulating cerebrovascular function in AD.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100482"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796721","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}