Pub Date : 2025-12-07DOI: 10.1016/j.cccb.2025.100523
Xuan Vinh To , Javier Urriola , Viktor Vegh , Patrick Donnelly , Liam Maclachlan , Kate Mahady , Eduardo Miguel Apellaniz , Ryan Lim , Guido Gonzalez , Ricardo Wenger , Paul Cumming , Craig Winter , Fatima Nasrallah
Objectives
Cerebral microbleeds (CMBs), which present as foci of hypointensities on T2*-weighted Magnetic Resonance Imaging (MRI) are associated with weakened vessel walls. CMBs are also a frequent finding in traumatic brain injury (TBI) in association with poor outcome. We investigated whether a combination of susceptibility weighted imaging (SWI) and dynamic contrast enhanced (DCE) MRI could accurately identify characteristics of CMBs that are most relevant to TBI.
Materials and Methods
Thirty TBI patients were recruited from a neurosurgical unit. We acquired structural three-dimensional T1-weighted, T2-weighted dark fluid, SWI, and DCE-MRI images on a 3T MRI. DCE-MRI data was fitted for a linear graphic (Patlak-Gjedde) model to calculate voxel-wise volume transfer constant (Ktrans) maps. Ktrans ranges of normal-appearing brain (NAB) areas were quantified and two sub-classes of CMBs—leaky and non-leaky CMBs—were identified. Characteristics and spatial distribution of the quantified imaging metrics and the immunological blood panel results were then compared across mild versus moderate–severe TBI groups, as classified by Glasgow Coma Scale.
Results
More severe TBI was associated with CMBs exhibiting leaky BBB as quantified by DCE-MRI. Higher blood levels of interferon gamma (IFN-γ) were associated with lower number of CMBs in TBI patients at more than 8 days post-TBI.
Discussion
combined DCE-MRI and SWI confirmed that CMBs with leaky BBBs are more prevalent in moderate-severe TBIs compared. Higher levels of IFN-γ appeared to have been associated with fewer CMBs in the sub-acute stage of TBI.
{"title":"Relevance of cerebral microbleeds with leaky blood brain barrier in traumatic brain injury and protective role of interferon-gamma: A cohort study","authors":"Xuan Vinh To , Javier Urriola , Viktor Vegh , Patrick Donnelly , Liam Maclachlan , Kate Mahady , Eduardo Miguel Apellaniz , Ryan Lim , Guido Gonzalez , Ricardo Wenger , Paul Cumming , Craig Winter , Fatima Nasrallah","doi":"10.1016/j.cccb.2025.100523","DOIUrl":"10.1016/j.cccb.2025.100523","url":null,"abstract":"<div><h3>Objectives</h3><div>Cerebral microbleeds (CMBs), which present as foci of hypointensities on T2*-weighted Magnetic Resonance Imaging (MRI) are associated with weakened vessel walls. CMBs are also a frequent finding in traumatic brain injury (TBI) in association with poor outcome. We investigated whether a combination of susceptibility weighted imaging (SWI) and dynamic contrast enhanced (DCE) MRI could accurately identify characteristics of CMBs that are most relevant to TBI.</div></div><div><h3>Materials and Methods</h3><div>Thirty TBI patients were recruited from a neurosurgical unit. We acquired structural three-dimensional T1-weighted, T2-weighted dark fluid, SWI, and DCE-MRI images on a 3T MRI. DCE-MRI data was fitted for a linear graphic (Patlak-Gjedde) model to calculate voxel-wise volume transfer constant (K<sup>trans</sup>) maps. K<sup>trans</sup> ranges of normal-appearing brain (NAB) areas were quantified and two sub-classes of CMBs—leaky and non-leaky CMBs—were identified. Characteristics and spatial distribution of the quantified imaging metrics and the immunological blood panel results were then compared across mild versus moderate–severe TBI groups, as classified by Glasgow Coma Scale.</div></div><div><h3>Results</h3><div>More severe TBI was associated with CMBs exhibiting leaky BBB as quantified by DCE-MRI. Higher blood levels of interferon gamma (IFN-γ) were associated with lower number of CMBs in TBI patients at more than 8 days post-TBI.</div></div><div><h3>Discussion</h3><div>combined DCE-MRI and SWI confirmed that CMBs with leaky BBBs are more prevalent in moderate-severe TBIs compared. Higher levels of IFN-γ appeared to have been associated with fewer CMBs in the sub-acute stage of TBI.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100523"},"PeriodicalIF":2.8,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712147","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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2024.100372
Katie Harris , Jessica Gong , Stephen MacMahon , Ying Xu , Sultana Shajahan , Stephen Harrap , Neil Poulter , Michel Marre , Pavel Hamet , Giuseppe Mancia , Craig Anderson , Mark Woodward , John Chalmers
Background and aims
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).
Methods
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 <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 <0.05 was regarded as statistically significant.
Results
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 (<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 (<10 years OR 0.92 (0.81–1.05) vs ≥10 years 1.16 (0.97–1.38); p for interaction 0.04).
Conclusions
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.
Clinical trial registration
ADVANCE is registered with ClinicalTrials.gov: number NCT00145925
背景和目的：越来越多的证据表明，降低高血压（BP）可以预防痴呆和轻度认知障碍（MCI）。此外，虽然糖尿病是痴呆和轻度认知障碍的危险因素，但强化血糖控制对这些终点的影响尚不确定。本研究旨在根据基线认知和其他特征确定降压（相对于安慰剂）和强化降糖（相对于标准对照）治疗对2型糖尿病（T2DM）患者痴呆和认知能力下降（CD）的影响。方法：在糖尿病和血管疾病中的作用：Preterax和Diamicron改良释放控制评价（ADVANCE）试验纳入11,140例T2DM患者。在基线迷你精神状态检查（MMSE）的亚组中，研究了降压和强化降糖治疗的效果，分为认知正常（评分≥28）和认知障碍(评分结果：降压治疗（与安慰剂相比）与认知障碍参与者的痴呆/CD发生率较低相关（OR 0.76, 95% CI(0.59-0.99)），但与认知正常参与者无关(OR 1.05, 95% CI (0.92-1.21)；P为相互作用0.03)。与安慰剂相比，那些有心肾代谢综合征病史的患者在痴呆/CD方面没有得到主动降压治疗的益处。降压治疗没有进一步的亚组效应。强化降糖（与标准对照）对痴呆/CD几率的影响在基线认知亚组中没有变化。然而，它确实因基线血糖水平而异(结论：这项研究表明，与认知功能正常的人相比，早期认知功能丧失的人降压治疗的效果更大。根据2型糖尿病患者的血糖水平和糖尿病病程，强化降糖对痴呆和CD的影响也存在差异。临床试验注册：ADVANCE在ClinicalTrials.gov注册：编号NCT00145925。
{"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 , Jessica Gong , Stephen MacMahon , Ying Xu , Sultana Shajahan , Stephen Harrap , Neil Poulter , Michel Marre , Pavel Hamet , Giuseppe Mancia , Craig Anderson , Mark Woodward , 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 <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 <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 (<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 (<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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2024.100376
Lina Jarutyte , Jan Petr , Nicholas Turner , Patrick G. Kehoe , Henk-Jan Mutsaerts , David L. Thomas
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.
动脉自旋标记（ASL）可以使用MRI对区域脑灌注进行无创量化。ASL被用于通过血管紧张素靶向（RADAR）减少阿尔茨海默病的病理（reduction Pathology in Alzheimer's Disease）多中心试验，以试点评估抗高血压药物氯沙坦对脑血流量（CBF）的影响。在多中心环境下，不同制造商扫描仪的ASL实施差异导致测量的CBF及其相关参数（例如CBF的空间变异系数（sCoV），动脉到达时间的代理）存在内在差异。此外，ASL采集参数设置的差异也会影响测量的定量灌注值。在这项研究中，我们使用RADAR队列的数据作为案例研究来评估CBF和sCoV的位点依赖性系统差异，并表明读出模块（2D或3D）和标记后延迟获取参数的变化引入了人工组差异。当在数据分析中考虑到这种影响时，我们表明仍然有可能将跨站点的ASL数据结合起来，以观察灰质CBF与认知评分之间的预期关系。总之，ASL可以在多中心治疗试验中提供与CBF差异相关的有用信息，但在数据分析中必须小心，以解释扫描仪类型和获取方案中不可避免的位点间差异。
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Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100382
Hinpetch Daungsupawong , Viroj Wiwanitkit
{"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 , 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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100395
Elmira Agah , Sarah T. Farias , David K. Johnson , Charles DeCarli , Pauline Maillard
Objective
To determine the independent and joint associations of five markers of white matter integrity, including white matter hyperintensities (WMH), extracellular free water (FW), fractional anisotropy (FA), peak width of skeletonized mean diffusivity (PSMD), and Diffusion tensor image analysis along the perivascular space index (ALPS) on cognitive performance and its trajectory in cognitively diverse individuals.
Methods
574 participants from the University of California, Davis Alzheimer’s Disease Research Center (UCD ADRC) longitudinal cohort, aged 77 ± 7 years received yearly comprehensive clinical evaluations and a baseline MRI exam. Baseline MRI measures, including WMH, FW, FA, PSMD, and ALPS, were computed for each individual and used as independent variables to explain baseline and change in episodic memory (EM) and executive function (EF) using linear regression with stepwise adjustment. Bayesian Model Averaging (BMA) was then applied to derive robust estimates of each marker’s contribution to cognition and its longitudinal trajectory, accounting for their joint inclusion in the same model.
Results
Analyses showed that higher baseline WMH, FW, and PSMD, as well as lower FA and ALPS, were significantly associated with poorer cognitive performance (p < 0.05). These associations remained robust after adjusting for relevant covariates—including age, sex, education, hypertension, diabetes, and hippocampal volume—except for FA and ALPS, which were no longer associated with EM (p > 0.05). Higher baseline WMH, FW, and PSMD, and lower FA, were also significantly associated with annual decline in EF and EM, whereas ALPS showed no association with cognitive change (p > 0.05). After covariate adjustment, these associations remained significant, except for PSMD and FA which were no longer significantly associated with EM trajectory. Joint modeling using BMA identified FW and WMH as the most likely contributors to both baseline performance and change in EF and EM, with posterior inclusion probabilities exceeding 50 %.
Conclusions
This study identified both cross-sectional and longitudinal associations between five markers of white matter integrity and cognitive performance and decline. Using BMA—a method designed to disentangle the specific contribution of each marker while accounting for multicollinearity—we found that, among the five markers, FW and WMH emerged as the most probable candidates to explain the course of cognitive decline in EM and EF.
{"title":"Disentangling the contributions of cerebrovascular-related white matter integrity markers to cognitive aging","authors":"Elmira Agah , Sarah T. Farias , David K. Johnson , Charles DeCarli , Pauline Maillard","doi":"10.1016/j.cccb.2025.100395","DOIUrl":"10.1016/j.cccb.2025.100395","url":null,"abstract":"<div><h3>Objective</h3><div>To determine the independent and joint associations of five markers of white matter integrity, including white matter hyperintensities (WMH), extracellular free water (FW), fractional anisotropy (FA), peak width of skeletonized mean diffusivity (PSMD), and Diffusion tensor image analysis along the perivascular space index (ALPS) on cognitive performance and its trajectory in cognitively diverse individuals.</div></div><div><h3>Methods</h3><div>574 participants from the University of California, Davis Alzheimer’s Disease Research Center (UCD ADRC) longitudinal cohort, aged 77 ± 7 years received yearly comprehensive clinical evaluations and a baseline MRI exam. Baseline MRI measures, including WMH, FW, FA, PSMD, and ALPS, were computed for each individual and used as independent variables to explain baseline and change in episodic memory (EM) and executive function (EF) using linear regression with stepwise adjustment. Bayesian Model Averaging (BMA) was then applied to derive robust estimates of each marker’s contribution to cognition and its longitudinal trajectory, accounting for their joint inclusion in the same model.</div></div><div><h3>Results</h3><div>Analyses showed that higher baseline WMH, FW, and PSMD, as well as lower FA and ALPS, were significantly associated with poorer cognitive performance (<em>p</em> < 0.05). These associations remained robust after adjusting for relevant covariates—including age, sex, education, hypertension, diabetes, and hippocampal volume—except for FA and ALPS, which were no longer associated with EM (p > 0.05). Higher baseline WMH, FW, and PSMD, and lower FA, were also significantly associated with annual decline in EF and EM, whereas ALPS showed no association with cognitive change (p > 0.05). After covariate adjustment, these associations remained significant, except for PSMD and FA which were no longer significantly associated with EM trajectory. Joint modeling using BMA identified FW and WMH as the most likely contributors to both baseline performance and change in EF and EM, with posterior inclusion probabilities exceeding 50 %.</div></div><div><h3>Conclusions</h3><div>This study identified both cross-sectional and longitudinal associations between five markers of white matter integrity and cognitive performance and decline. Using BMA—a method designed to disentangle the specific contribution of each marker while accounting for multicollinearity—we found that, among the five markers, FW and WMH emerged as the most probable candidates to explain the course of cognitive decline in EM and EF.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100395"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104767","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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100397
M.H. Snijders , E. Janssen , E. Verburgt , A. ter Telgte , T.N.A. van den Berg , M.C. Maas , F.J.A. Meijer , A.M. Tuladhar , N.P. Riksen , J. Deinum , F.E. de Leeuw
Introduction
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.
Methods
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 t-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.
Results
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]; p < 0.001). Hypertension increased odds of deep WMH (OR 5.49, p = 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, p = 0.111) after adjusting for age.
Conclusion
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.
脑血管病（cSVD）与脑卒中和认知能力下降有关，cSVD的MRI标志物随着年龄的增长而增加。高血压是老年人心血管疾病的重要危险因素，但其对年轻人的影响尚不清楚。本研究探讨了与血压正常的对照组相比，年轻高血压患者中心血管疾病的MRI标志物是否更为普遍。方法在这项横断面研究中，60例高血压患者和21例年龄在18-55岁的对照组接受了3T MRI检查，以评估心血管疾病标志物：白质高强度（WMH）、腔隙和微出血。采用t检验、卡方检验或非参数方法评估组间差异。我们使用多变量回归模型，包括线性、逻辑、有序逻辑和惩罚逻辑回归，对潜在的混杂因素进行调整，研究了血压和cSVD标志物之间的关系。结果高血压患者年龄较大（IQR中位数为35.6（29.6-41.4）岁vs 29.2（27.8-33.2）岁），BMI较高，文化程度较低，女性比例相近。高血压参与者的深度WMH负担显著更高（Fazekas评分中位数：1 [IQR: 0 - 1] vs 0 [IQR: 0 - 0]； p < 0.001）。高血压增加深部WMH的发生率（OR 5.49, p = 0.011）。腔隙和微出血是罕见的，仅在高血压参与者中观察到。调整年龄后，高血压诊断后的持续时间与WMH体积无显著相关性（β=7.27, p = 0.111）。结论青壮年高血压患者多发wmh，提示早期脑微血管改变。这些发现强调了早期发现和治疗高血压对于潜在地预防长期脑血管改变的重要性。
{"title":"On the origin of cerebral small vessel disease: MRI markers of cSVD in young adults with hypertension","authors":"M.H. Snijders , E. Janssen , E. Verburgt , A. ter Telgte , T.N.A. van den Berg , M.C. Maas , F.J.A. Meijer , A.M. Tuladhar , N.P. Riksen , J. Deinum , 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> < 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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100396
Jolene Phelps , Manpreet Singh , Cheryl R. McCreary , Caroline Dallaire-Théroux , Ryan G. Stein , Zacharie Potvin-Jutras , Dylan X. Guan , Jeng-liang D. Wu , Amelie Metz , Eric E. Smith
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 (e.g., 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.
脑小血管疾病（CSVD）可表现为磁共振成像上可见的脑病变，包括白质高信号（WMH）、脑微出血（CMB）、血管周围间隙（PVS）、腔隙和近期皮质下小梗死（RSSI）。检测和分割这些成像标记可以提供有关大脑健康的宝贵信息，包括预防和治疗痴呆症。然而，人工分割是很麻烦的，特别是对于研究中的大型队列。人们对使用机器学习的自动化工具的开发进行了广泛的研究，以提高病变分割的准确性和效率。本系统综述旨在总结过去10年来开发的新的自动化方法，这些方法用于分割CSVD病变类型，并已在CSVD患者或高危人群（例如，老年人、认知障碍患者或有血管危险因素的人群）中得到验证。在Web of Science和PubMed上搜索得到2764项研究，其中89项是经过筛选和全文审查后纳入的。其中59种方法对WMH进行了分割，23种方法对CMB进行了检测或分类，6种方法对PVS进行了检测或分割，5种方法对lacunes进行了检测、分类或分割，2种方法对RSSI进行了分割。在这些研究中，有30项研究（23项关于WMH， 5项关于CMB， 1项关于pv， 1项关于lacunes）包括下载代码或预训练模型的链接，其中包括一个商业工具，以及一个依赖于商业工具输入的模型。总的来说，本综述发现了用于WMH分割的高质量工具的良好证据，而用于准确分割其他CSVD病变类型的工具较少。
{"title":"Cerebral small vessel disease lesion segmentation methods: A systematic review","authors":"Jolene Phelps , Manpreet Singh , Cheryl R. McCreary , Caroline Dallaire-Théroux , Ryan G. Stein , Zacharie Potvin-Jutras , Dylan X. Guan , Jeng-liang D. Wu , Amelie Metz , 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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100391
Frank J. Wolters , Meike W. Vernooij , Gennady V. Roshchupkin , M․Arfan Ikram , Maryam Kavousi , Peter J. Koudstaal , Aad van der Lugt , Daniel Bos
Background
Carotid artery stenosis could contribute to gradual loss of brain function through chronic hypoxia and ischemia.
Methods
We included consecutive participants of the population-based Rotterdam Study with unilateral ≥50 % stenosis at the carotid artery bifurcation on time-of-flight carotid MR angiography, and compared between hemispheres the presence of ischemic lesions, tissue volumes, and white matter integrity on structural brain MRI.
Results
Among 50 participants (mean age 76 years, 50 % women), flow was lower in the affected carotid artery than on the unaffected side (160mL/min versus 202mL/min; flow reduction [95 %CI] per 1 % increase in stenosis: 1.7 mL/min [1.0–2.5]). Twelve individuals had radiographic evidence of cortical infarction, of whom 8 had cortical microinfarcts, all on the side of the stenosis (P = 0.001). Downstream of the stenotic artery, parenchymal volume was lower than in the contralateral hemisphere (mean difference: -2.7 mL [-4.9;-0.4]), similar for grey and white matter. Differences were most profound in the frontoparietal lobes, and increased with severity of stenosis to roughly 5 mL in individuals with ≥70 % stenosis. White matter hyperintensity volume and microstructural integrity did not differ between hemispheres.
Conclusions
Carotid artery stenosis is associated with downstream presence of cortical microinfarcts as well as lower parenchymal tissue volume.
{"title":"Effect of carotid artery stenosis on cortical microinfarcts, white matter integrity, and brain volume: An interhemispheric comparison within the population-based Rotterdam Study","authors":"Frank J. Wolters , Meike W. Vernooij , Gennady V. Roshchupkin , M․Arfan Ikram , Maryam Kavousi , Peter J. Koudstaal , Aad van der Lugt , Daniel Bos","doi":"10.1016/j.cccb.2025.100391","DOIUrl":"10.1016/j.cccb.2025.100391","url":null,"abstract":"<div><h3>Background</h3><div>Carotid artery stenosis could contribute to gradual loss of brain function through chronic hypoxia and ischemia.</div></div><div><h3>Methods</h3><div>We included consecutive participants of the population-based Rotterdam Study with unilateral ≥50 % stenosis at the carotid artery bifurcation on time-of-flight carotid MR angiography, and compared between hemispheres the presence of ischemic lesions, tissue volumes, and white matter integrity on structural brain MRI.</div></div><div><h3>Results</h3><div>Among 50 participants (mean age 76 years, 50 % women), flow was lower in the affected carotid artery than on the unaffected side (160mL/min versus 202mL/min; flow reduction [95 %CI] per 1 % increase in stenosis: 1.7 mL/min [1.0–2.5]). Twelve individuals had radiographic evidence of cortical infarction, of whom 8 had cortical microinfarcts, all on the side of the stenosis (<em>P</em> = 0.001). Downstream of the stenotic artery, parenchymal volume was lower than in the contralateral hemisphere (mean difference: -2.7 mL [-4.9;-0.4]), similar for grey and white matter. Differences were most profound in the frontoparietal lobes, and increased with severity of stenosis to roughly 5 mL in individuals with ≥70 % stenosis. White matter hyperintensity volume and microstructural integrity did not differ between hemispheres.</div></div><div><h3>Conclusions</h3><div>Carotid artery stenosis is associated with downstream presence of cortical microinfarcts as well as lower parenchymal tissue volume.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100391"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750242","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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100393
Benno Gesierich , Lukas Pirpamer , Dominik S Meier , Michael Amann , Minne N Cerfontaine , Frank-Erik de Leeuw , Pauline Maillard , Sue Moy , Karl G. Helmer , Michael Kühne , Leo H Bonati , Julie W Rutten , Saskia A.J. Lesnik Oberstein , Marco Duering , Alzheimer’s Disease Neuroimaging Initiative
Introduction
White matter hyperintensities (WMH) on MRI are a hallmark of cerebral small vessel disease. Although numerous WMH segmentation tools exist, each presents relevant limitations that can impact their usability. This research aimed to develop, validate, and disseminate a novel WMH segmentation algorithm to address these limitations.
Methods
Using an intentionally heterogeneous dataset, we trained models based on the MD-GRU and nnU-Net deep learning algorithms. The new models were benchmarked in both technical and clinical validation against current state-of-the-art algorithms, utilizing datasets that were not included in the training data. For technical validation in patients, we assessed bias and precision against reference masks, scan-rescan repeatability and inter-scanner reproducibility in data from the MarkVCID consortium. Segmentation performance on 2D data was evaluated using the SWISS-AF dataset. For clinical validation, we determined percent volume change over a two-year follow-up in the DiViNAS study and calculated statistical power to detect treatment effects.
Results
The newly trained algorithms outperformed the benchmarking algorithms, demonstrating better agreement with reference volumes, as well as less bias and higher precision in the repeatability and reproducibility experiments. The nnU-Net algorithm exhibited the highest statistical power for detecting treatment effects, requiring a 41 % smaller sample size than the best-performing benchmarking algorithm.
Conclusion
We developed and systematically validated two novel WMH segmentation algorithms, which demonstrated excellent generalization capabilities. The comprehensive, user-friendly processing pipelines are publicly available as prebuilt software containers and can be applied to a wide range of datasets without re-training or modifications.
{"title":"Technical and clinical validation of a novel deep learning-based white matter hyperintensity segmentation tool","authors":"Benno Gesierich , Lukas Pirpamer , Dominik S Meier , Michael Amann , Minne N Cerfontaine , Frank-Erik de Leeuw , Pauline Maillard , Sue Moy , Karl G. Helmer , Michael Kühne , Leo H Bonati , Julie W Rutten , Saskia A.J. Lesnik Oberstein , Marco Duering , Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.cccb.2025.100393","DOIUrl":"10.1016/j.cccb.2025.100393","url":null,"abstract":"<div><h3>Introduction</h3><div>White matter hyperintensities (WMH) on MRI are a hallmark of cerebral small vessel disease. Although numerous WMH segmentation tools exist, each presents relevant limitations that can impact their usability. This research aimed to develop, validate, and disseminate a novel WMH segmentation algorithm to address these limitations.</div></div><div><h3>Methods</h3><div>Using an intentionally heterogeneous dataset, we trained models based on the MD-GRU and nnU-Net deep learning algorithms. The new models were benchmarked in both technical and clinical validation against current state-of-the-art algorithms, utilizing datasets that were not included in the training data. For technical validation in patients, we assessed bias and precision against reference masks, scan-rescan repeatability and inter-scanner reproducibility in data from the MarkVCID consortium. Segmentation performance on 2D data was evaluated using the SWISS-AF dataset. For clinical validation, we determined percent volume change over a two-year follow-up in the DiViNAS study and calculated statistical power to detect treatment effects.</div></div><div><h3>Results</h3><div>The newly trained algorithms outperformed the benchmarking algorithms, demonstrating better agreement with reference volumes, as well as less bias and higher precision in the repeatability and reproducibility experiments. The nnU-Net algorithm exhibited the highest statistical power for detecting treatment effects, requiring a 41 % smaller sample size than the best-performing benchmarking algorithm.</div></div><div><h3>Conclusion</h3><div>We developed and systematically validated two novel WMH segmentation algorithms, which demonstrated excellent generalization capabilities. The comprehensive, user-friendly processing pipelines are publicly available as prebuilt software containers and can be applied to a wide range of datasets without re-training or modifications.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100393"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007668","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}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100377
Yunfei Li, Linus Jönsson
Brain disorders are prevalent across all age groups but particularly in the elderly, highlighting the importance of preserving brain health in ageing populations. There have been few previous studies to address the complete scope of burden of brain disorders, including direct and indirect costs as well as intangible costs from morbidity and mortality. We seek to illustrate the full health and economic impact of brain disorders by leveraging data from previous large-scale epidemiological and health economic studies to estimate the total direct, indirect and intangible cost of brain disorders in 2019. Two alternative methods were used to estimate indirect costs: the human capital (HC) method (data from the CBDE2010 study), and the willingness-to-pay (WTP) per DALY method (data from GBD2019). Less than 10% of the costs of Alzheimer's disease (AD) and other dementias are incurred by the health care system, while Alzheimer's disease and other dementias is the costliest condition using the HC approach and stroke is the costliest condition due to the large number of life-years lost, followed by AD using the WTP approach. Using per-capita GDP as a proxy for WTP, the indirect costs were nearly four times higher compared to the conventional HC approach. We found that Indirect costs of brain disorders outweigh the direct costs for diagnosis, treatment and care even in high-income countries with advanced, universally accessible systems in Europe. There is likely underinvestment in R&D for brain disorders, and health care systems may lack sufficient incentives to invest in their treatment and prevention.
{"title":"The health and economic burden of brain disorders: Consequences for investment in diagnosis, treatment, prevention and R&D","authors":"Yunfei Li, Linus Jönsson","doi":"10.1016/j.cccb.2025.100377","DOIUrl":"10.1016/j.cccb.2025.100377","url":null,"abstract":"<div><div>Brain disorders are prevalent across all age groups but particularly in the elderly, highlighting the importance of preserving brain health in ageing populations. There have been few previous studies to address the complete scope of burden of brain disorders, including direct and indirect costs as well as intangible costs from morbidity and mortality. We seek to illustrate the full health and economic impact of brain disorders by leveraging data from previous large-scale epidemiological and health economic studies to estimate the total direct, indirect and intangible cost of brain disorders in 2019. Two alternative methods were used to estimate indirect costs: the human capital (HC) method (data from the CBDE2010 study), and the willingness-to-pay (WTP) per DALY method (data from GBD2019). Less than 10% of the costs of Alzheimer's disease (AD) and other dementias are incurred by the health care system, while Alzheimer's disease and other dementias is the costliest condition using the HC approach and stroke is the costliest condition due to the large number of life-years lost, followed by AD using the WTP approach. Using per-capita GDP as a proxy for WTP, the indirect costs were nearly four times higher compared to the conventional HC approach. We found that Indirect costs of brain disorders outweigh the direct costs for diagnosis, treatment and care even in high-income countries with advanced, universally accessible systems in Europe. There is likely underinvestment in R&D for brain disorders, and health care systems may lack sufficient incentives to invest in their treatment and prevention.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100377"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082356","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}
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