Cerebral circulation - cognition and behavior最新文献

{"title":"Vascular cognitive impairment in China: Epidemiology, risk factors, healthcare system, management challenges, therapeutic modalities, and prevention strategies","authors":"Liang Gong,&nbsp;Hongmei Lang,&nbsp;Jie Yang","doi":"10.1016/j.cccb.2026.100563","DOIUrl":"10.1016/j.cccb.2026.100563","url":null,"abstract":"<div><div>Vascular cognitive impairment (VCI) is an increasingly important contributor to cognitive decline in China, where rapid population aging intersects with a substantial burden of stroke, cerebral small vessel disease, and cardiometabolic risk. This narrative review synthesizes Chinese epidemiological, clinical, health-services, and policy literature on VCI, supplemented by key international consensus and interventional evidence when directly relevant. Available evidence indicates that the vascular contribution to cognitive disorders in China is substantial but heterogeneously measured because of differences in case definition, screening tools, study setting, and follow-up design. Post-stroke cognitive impairment is especially important because it is common, clinically recognizable, and reachable through existing stroke follow-up pathways. Across studies, hypertension and cardiometabolic multimorbidity emerge as the most actionable modifiable drivers. China has strengthened its policy response through updated clinical guidance and a national dementia action plan, yet implementation remains constrained by inconsistent screening, uneven specialist capacity, fragmented referral pathways, and limited longitudinal follow-up. Therapeutically, direct evidence for interventions targeting established VCI syndromes remains limited. The strongest available support is indirect and comes from vascular risk reduction, particularly blood pressure lowering for broader dementia or cognitive decline endpoints, while multidomain and symptomatic interventions show phenotype-specific but more heterogeneous signals. A practical China-adapted response is therefore a tiered life-course model linking chronic disease management, post-stroke surveillance, specialist diagnosis, multidomain intervention, and caregiver support. Future priorities include harmonized diagnostics, clearer evidence characterization, biomarker-enabled longitudinal cohorts, and pragmatic implementation-science studies focused on adaptation, cost, and sustainability in community and rural settings.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"11 ","pages":"Article 100563"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119171","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":"Arterial spin labeling MRI in CADASIL: Implications for cerebral small vessel disease and therapeutic trials","authors":"Masafumi Ihara ,&nbsp;Satoshi Saito ,&nbsp;Satoru Fujiwara ,&nbsp;Tomotaka Tanaka ,&nbsp;Toshihiko Aso","doi":"10.1016/j.cccb.2026.100542","DOIUrl":"10.1016/j.cccb.2026.100542","url":null,"abstract":"<div><div>Cerebral small vessel disease (CSVD) is a major cause of lacunar stroke, vascular cognitive impairment, and gait disturbance, yet the development of disease-modifying therapies is limited by the lack of robust, non-invasive biomarkers of microvascular pathology. Arterial spin labeling (ASL) MRI enables quantitative, non-invasive, contrast-free measurement of cerebral blood flow (CBF) and is well suited for longitudinal studies. In routine clinical and research practice, single-delay three-dimensional pseudo-continuous ASL (pCASL) with an appropriately long post-labeling delay is the workhorse implementation and has already been applied in several CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and hereditary CSVD cohorts, while more advanced approaches such as multi-delay ASL and diffusion-prepared pCASL can additionally probe arterial transit time (ATT) and blood–brain barrier (BBB) water exchange. CADASIL, caused by pathogenic <em>NOTCH3</em> variants, is a prototypical monogenic CSVD with relatively low etiologic heterogeneity, providing a powerful clinical model in which to study microvascular dysfunction and trial-ready imaging markers. In this review, we synthesize data on ASL in CADASIL, including relationships between CBF, cognition, and lesion burden, evidence from acute encephalopathic episodes, and emerging work on ATT and BBB water exchange. We further compare perfusion profiles across monogenic (<em>HTRA1</em>-related CSVD, Fabry disease) and sporadic CSVD, and discuss how ASL-derived measures—CBF, ATT, and BBB water exchange rate—can be incorporated as imaging endpoints in CADASIL therapeutic trials. In particular, standardized single-delay three-dimensional pCASL provides a practical, scalable method to quantify regional CBF as a primary perfusion endpoint.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100542"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147709808","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":"Determinants of cerebral microbleed presence and burden in CADASIL","authors":"Jessica Lebenberg ,&nbsp;Louis Lambert ,&nbsp;Laura Tintoré-Carbonell ,&nbsp;Mohamed Saichi ,&nbsp;Antoine Guillonet ,&nbsp;Hugues Chabriat","doi":"10.1016/j.cccb.2026.100547","DOIUrl":"10.1016/j.cccb.2026.100547","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Cerebral microbleeds (CMBs) are observed in one-third of CADASIL patients and increase with age. Factors associated with CMBs vary across studies, likely due to inadequate handling of their zero-inflated, long-tailed distribution and lack of accounting for measurement variability. We aimed to assess these factors while addressing these limitations.</div></div><div><h3>Methods</h3><div>CMBs were assessed in a large CADASIL cohort, with demographic, vascular, genetic, imaging, and clinical data. White matter hyperintensity volume (WMH), lacune count, and brain parenchymal fraction (BPF) were measured. A Hurdle model was used to distinguish factors associated with CMB presence from those related to lesion counts, while accounting for measurement variability. Three models were built with: (1) demographic/biological factors; (2) MRI markers; and (3) clinical variables.</div></div><div><h3>Results</h3><div>Beyond the consistent effect of the MRI sequence, in Model 1, CMB presence was associated with age, male sex and hypertension, while counts were associated only with age. In Model 2, CMB presence was associated with age, hypertension, and lacune count; counts were higher with WMH and antiplatelet use, and lower with EGFr 1–6 mutations and BPF. In Model 3, CMB presence was associated with age, hypertension, stroke history and gait disturbances; counts were associated with education, lacune count, MMSE ≤24, and hypercholesterolemia measured at the study visit.</div></div><div><h3>Conclusions</h3><div>Hurdle modeling distinguishes determinants of CMB occurrence from accumulation. Hypertension appears to lower the threshold for lesion emergence along aging. CMB burden is associated with the burden of cerebrovascular lesions, brain atrophy and clinical severity, supporting worsening of the microangiopathic process, with specific impact related to mutation type.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100547"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184355","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":"Effect of randomised blood pressure lowering treatment and intensive glucose control on dementia and cognitive decline according to baseline cognitive function and other subpopulations of individuals with type 2 diabetes: Results from the ADVANCE trial","authors":"Katie Harris ,&nbsp;Jessica Gong ,&nbsp;Stephen MacMahon ,&nbsp;Ying Xu ,&nbsp;Sultana Shajahan ,&nbsp;Stephen Harrap ,&nbsp;Neil Poulter ,&nbsp;Michel Marre ,&nbsp;Pavel Hamet ,&nbsp;Giuseppe Mancia ,&nbsp;Craig Anderson ,&nbsp;Mark Woodward ,&nbsp;John Chalmers","doi":"10.1016/j.cccb.2024.100372","DOIUrl":"10.1016/j.cccb.2024.100372","url":null,"abstract":"<div><h3>Background and aims</h3><div>Accumulating evidence indicates that reducing high blood pressure (BP) prevents dementia and mild cognitive impairment (MCI). Furthermore, although diabetes is a risk factor for dementia and MCI, there is uncertainty of the effect of intensive glucose control on these endpoints. This study aimed to determine the effects of BP-lowering (vs placebo) and intensive glucose-lowering (vs standard control) treatments according to baseline cognition and other characteristics on dementia and cognitive decline (CD) in people with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial involved 11,140 individuals with T2DM. The effects of BP-lowering and intensive glucose-lowering treatments were explored in subgroups of baseline Mini-Mental State Examination (MMSE), categorised as cognitively normal (scores ≥28) and cognitive impairment (scores &lt;28). The primary outcome was a composite of dementia/CD that accounted for the competing risk of death. Multinomial regression models, adjusted for common cardiovascular risk factors, were used to estimate odds ratios (OR) with 95 % confidence intervals (CI) of the effects of the treatments on dementia/CD. Homogeneity of effects by subgroups were evaluated using interaction terms in the models. A two-sided p value &lt;0.05 was regarded as statistically significant.</div></div><div><h3>Results</h3><div>BP-lowering treatment (vs. placebo) was associated with a lower odds of dementia/CD in participants with cognitive impairment (OR 0.76, 95 % CI (0.59–0.99)) but not in those cognitively normal (OR 1.05, 95 % CI (0.92–1.21); p for interaction 0.03). Those with a history of cardio-renal-metabolic syndrome did not experience a benefit of active BP lowering treatment compared with placebo on dementia/CD. There were no further subgroup effects of BP-lowering treatment. The effect of intensive glucose lowering (vs standard control) on the odds of dementia/CD did not vary by baseline cognition subgroup. However, it did vary by level of blood glucose at baseline (&lt;7.9 mmol/L OR 1.12, 95 % CI (0.96–1.30) vs ≥ 7.9 mmol/L 0.87 (0.75–1.00); p for interaction 0.02) and duration of T2DM (&lt;10 years OR 0.92 (0.81–1.05) vs ≥10 years 1.16 (0.97–1.38); p for interaction 0.04).</div></div><div><h3>Conclusions</h3><div>This study suggests greater effects of BP-lowering treatment in those with early loss of cognitive function than in those cognitively normal. There were also differential effects of intensive glucose-lowering on dementia and CD according to levels of blood glucose and duration of diabetes in people with T2DM.</div></div><div><h3>Clinical trial registration</h3><div>ADVANCE is registered with ClinicalTrials.gov: number NCT00145925</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100372"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933801","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":"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":"A Novel Mouse Model for Investigating ARIAs in Response to Anti-Abeta Immunotherapy","authors":"Christian Crouzet ,&nbsp;Jihua Liu ,&nbsp;Bernard Choi ,&nbsp;David H Cribbs","doi":"10.1016/j.cccb.2025.100475","DOIUrl":"10.1016/j.cccb.2025.100475","url":null,"abstract":"<div><h3>Introduction</h3><div>Introduction: Three Alzheimer disease-modifying anti-Aβ antibodies (aducanumab, lecanemab, and donanemab) have been approved since 2021. However, Amyloid Related Imaging Abnormalities (ARIAs) remain problematic, with rare serious adverse events and deaths linked to amyloid-immunotherapy (six deaths from macro- hemorrhages and eight from severe inflammatory ARIA-E). Investigating the underlying adverse cerebrovascular responses to passive anti-Aβ immunotherapy is critical to improve patient safety. The mechanisms driving these potentially fatal events remain poorly understood, necessitating robust preclinical models. This study aimed to investigate ARIAs following Ab immunotherapy in 5XFAD mice with different genetic backgrounds to develop better models for studying adverse cerebrovascular responses.</div></div><div><h3>Methods</h3><div>Methods: Study 1: Ten 8-10-month-old 5XFAD.WSB.EiJ female mice received single IP injections of 3D6 anti-Aβ antibody (7.0 mg/kg), and five received IgG2a(k) isotype control (BioXCell). The 3D6.IgG2a monoclonal (from Dr. Ron Demattos, Eli Lilly) offers strong FcgR-mediated response with weak inhibitory activity and complement activation capability. Blood vessels were labeled with Lectin-Dylight-649 via retro-orbital injection.</div><div>Amyloid plaques and CAA were labeled with Amylo-glo RTD and H&amp;E staining detected vasculitis/angiitis. Study 2: Earlier time points (12, 24, 36 hours) compared 5XFAD.WSB.EiJ versus 5XFAD.C57B/6J responses to 3D6.IgG2a (5 mice/timepoint). Evans blue assessed blood-brain barrier integrity loss.</div></div><div><h3>Results</h3><div>Results: Study 1 was designed for 8 weeks with weekly 3D6.IgG2a injections, but was aborted after the first injection when 7/10 mice died within 36 hours. The remaining 3 mice were perfused to salvage data. All 3D6.IgG2a-treated brains showed surface macro- hemorrhages (Figure 1), while the IgG2a controls had no visible bleeds. Study 2 revealed striking strain differences: 5XFAD.C57B/6J mice were resistant to 3D6.IgG2a at all timepoints, while 5XFAD.WSB.EiJ brains showed modest surface lesions at 12 hours, prominent hemorrhages by 24 hours, and distress signs by 27 hours.</div></div><div><h3>Conclusions</h3><div>Conclusions: Comparing anti-Ab immunotherapy responses between 5XFAD.C57B/6J versus 5XFAD.WSB.EiJ mice provide insights into aging, amyloid plaque, and CAA contributions to ARIA development. The 3D6 antibody was chosen because its humanized version (bapineuzumab) previously reduced Aβ pathology while inducing ARIA-E and ARIA-H in patients. ARIA-like responses in 5XFAD.WSB.EiJ mice may provide a valuable model for investigating causes of serious adverse events in human amyloid immunotherapy patients.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100475"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796638","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":"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":"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":"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}