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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 根据基线认知功能和其他2型糖尿病患者亚群,随机降压治疗和强化血糖控制对痴呆和认知能力下降的影响:ADVANCE试验的结果
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 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 ,&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}
引用次数: 0
Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Experience from the RADAR study
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 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.
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引用次数: 0
Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Comment
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100382
Hinpetch Daungsupawong , Viroj Wiwanitkit
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引用次数: 0
The health and economic burden of brain disorders: Consequences for investment in diagnosis, treatment, prevention and R&D
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 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,&nbsp;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&amp;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}
引用次数: 0
Measuring cerebrovascular reactivity in a hemodialysis cohort
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100380
Claire Seigworth , Isabelle Grassl , Dawn F. Wolfgram
Introduction Cerebrovascular reactivity (CVR) can inform about cerebral vascular health and provide prognostic information on risk cerebral ischemic injury. Use of transcranial Doppler ultrasound (TCD) is a non-invasive and inexpensive method to measure CVR and often uses a stimulus of increase in arterial partial pressure of carbon dioxide (pCO2). We evaluate re-breathing and breath-hold to measure CVR in a medically complex hemodialysis cohort who are at risk for cerebral hypoperfusion due to circulatory stress of hemodialysis.
Methods CVR was measured using both a 30 s breath-hold and a re-breathing period. We used percent change in mean flow velocity of the middle cerebral artery, measured with TCD over the change in end-tidal CO2 to calculate CVR. Paired T-test was used to compare the parameters of CVR and Pearson correlation to evaluate relevant risk factors for lower CVR.
Results 16 participants completed both CVR measurements, with mean (SD) age of 64.2 (11.2) years. CVR measured from each technique was similar 3.4 (2.9) %/mmHg (breath-hold) vs 2.7 (1.6) %/mmHg, (re-breathing) p = 0.37. Older age and history of stroke were associated with lower CVR when measured with re-breathing but not with breath-hold technique.
Conclusions Re-breathing to increase pCO2 and measure CVR is well-tolerated by a frail older medically complex patient population and may be a way to measure cerebrovascular health.
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引用次数: 0
Permutations of cerebrovascular pathologies in older adults with and without diabetes
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100381
Rupal I. Mehta, Ana W. Capuano, Roshni Biswas, David A. Bennett, Zoe Arvanitakis
Permutations of cerebrovascular pathologies (CVP) in persons with diabetes mellitus (DM) have not been comprehensively investigated. Here, we examine diverse postmortem CVP outcomes, including permutations of single or mixed CVP, in 2163 older adults with or without DM who were followed in longitudinal studies of aging. Annual clinical evaluations included data to classify DM status by medical history (DM diagnosis), direct medication inspection (anti-diabetic therapy), and hemoglobin A1C level (≥6.5 %). Upon death, neuropathological examinations were performed and included evaluation for CVP (considering vessel pathologies and brain infarcts) and Alzheimer's disease neuropathologic change (AD-NC). Among all participants [mean age, 89.49 ± 6.89 years (SD)], single CVP were more common than mixed CVP. Logistic regression was used to analyze the association of DM with CVP permutations, controlling for age at death, sex, education, and AD-NC, and revealed increased odds of microinfarcts alone (odds ratio, 1.56 [95 %CI, 1.03–2.35]) and mixed microinfarcts and macroinfarcts (odds ratio, 1.90 [95 %CI, 1.16–3.13]). These associations remained after adjusting for demographic factors and cohort or vascular comorbidities including stroke, heart disease, hypertension, claudication, smoking, and systolic blood pressure. Furthermore, after controlling for demographic factors as well as AD-NC and APOE type, mixed microinfarcts and macroinfarcts were associated with approximate threefold increased risk of dementia (odds ratio, 2.95 [95 %CI, 1.13–7.70]) in participants with DM. Evidence suggests that older adults living with DM have higher odds of microinfarcts and mixed microinfarcts and macroinfarcts in the absence of intracranial vessel pathologies that cannot be explained by vascular comorbidities, and in this population mixed microinfarcts and macroinfarcts are associated with higher odds of dementia.
{"title":"Permutations of cerebrovascular pathologies in older adults with and without diabetes","authors":"Rupal I. Mehta,&nbsp;Ana W. Capuano,&nbsp;Roshni Biswas,&nbsp;David A. Bennett,&nbsp;Zoe Arvanitakis","doi":"10.1016/j.cccb.2025.100381","DOIUrl":"10.1016/j.cccb.2025.100381","url":null,"abstract":"<div><div>Permutations of cerebrovascular pathologies (CVP) in persons with diabetes mellitus (DM) have not been comprehensively investigated. Here, we examine diverse postmortem CVP outcomes, including permutations of single or mixed CVP, in 2163 older adults with or without DM who were followed in longitudinal studies of aging. Annual clinical evaluations included data to classify DM status by medical history (DM diagnosis), direct medication inspection (anti-diabetic therapy), and hemoglobin A1C level (≥6.5 %). Upon death, neuropathological examinations were performed and included evaluation for CVP (considering vessel pathologies and brain infarcts) and Alzheimer's disease neuropathologic change (AD-NC). Among all participants [mean age, 89.49 ± 6.89 years (SD)], single CVP were more common than mixed CVP. Logistic regression was used to analyze the association of DM with CVP permutations, controlling for age at death, sex, education, and AD-NC, and revealed increased odds of microinfarcts alone (odds ratio, 1.56 [95 %CI, 1.03–2.35]) and mixed microinfarcts and macroinfarcts (odds ratio, 1.90 [95 %CI, 1.16–3.13]). These associations remained after adjusting for demographic factors and cohort or vascular comorbidities including stroke, heart disease, hypertension, claudication, smoking, and systolic blood pressure. Furthermore, after controlling for demographic factors as well as AD-NC and APOE type, mixed microinfarcts and macroinfarcts were associated with approximate threefold increased risk of dementia (odds ratio, 2.95 [95 %CI, 1.13–7.70]) in participants with DM. Evidence suggests that older adults living with DM have higher odds of microinfarcts and mixed microinfarcts and macroinfarcts in the absence of intracranial vessel pathologies that cannot be explained by vascular comorbidities, and in this population mixed microinfarcts and macroinfarcts are associated with higher odds of dementia.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100381"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682581","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}
引用次数: 0
The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100383
Naomi Vlegels , Hilde van den Brink , Anna Kopczak , Tine Arts , Stanley D.T. Pham , Jeroen C.W. Siero , Benno Gesierich , Alberto De Luca , Marco Duering , Jaco J.M. Zwanenburg , Martin Dichgans , Geert Jan Biessels
In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients.
We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter.
Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (p = 0.04) and in the basal ganglia in sporadic cSVD (p = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter.
These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury.
{"title":"The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study","authors":"Naomi Vlegels ,&nbsp;Hilde van den Brink ,&nbsp;Anna Kopczak ,&nbsp;Tine Arts ,&nbsp;Stanley D.T. Pham ,&nbsp;Jeroen C.W. Siero ,&nbsp;Benno Gesierich ,&nbsp;Alberto De Luca ,&nbsp;Marco Duering ,&nbsp;Jaco J.M. Zwanenburg ,&nbsp;Martin Dichgans ,&nbsp;Geert Jan Biessels","doi":"10.1016/j.cccb.2025.100383","DOIUrl":"10.1016/j.cccb.2025.100383","url":null,"abstract":"<div><div>In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients.</div><div>We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter.</div><div>Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (<em>p</em> = 0.04) and in the basal ganglia in sporadic cSVD (<em>p</em> = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter.</div><div>These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100383"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726097","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}
引用次数: 0
Mid-life association between cardiovascular risk factors and cerebral blood flow in a multi-ethnic population
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100384
Esther M.C. Vriend , Mathijs B.J. Dijsselhof , Thomas A. Bouwmeester , Oscar H. Franco , Henrike Galenkamp , Didier Collard , Aart J. Nederveen , Bert-Jan H. van den Born , Henk J.M.M. Mutsaerts

Background

Cardiovascular (CV) risk factors are associated with cerebrovascular damage and cognitive decline in late-life. However, it is unknown how different ethnic CV risk profiles relate to cerebral haemodynamics in mid-life. We aimed to investigate associations of CV risk factors with cerebral haemodynamics at two timepoints and examine the impact of ethnicity on these measures.

Methods

From the HELIUS study (53.0 years, 44.8 % female), participants of Dutch (n = 236), Moroccan (n = 122), or South-Asian Surinamese (n = 173) descent were included. Cerebral blood flow (CBF) and its spatial coefficient of variation (sCoV, an ASL-label arrival measure of macrovascular efficiency) were obtained in grey (GM) and white matter (WM). CV risk factors were assessed 8.4 years [7.4–9.5] (first visit) and 2.2 years [1.8–2.6] (second visit) prior to MRI. Associations of CV risk factors, WM hyperintensities (WMH), and carotid plaques with cerebral haemodynamics were investigated using linear regressions.

Results

CBF and sCoV differed per ethnicity. Only at the second visit associations were found, without an interaction with ethnicity; history of CV disease with lower GM CBF and higher WM sCoV, higher total cholesterol and lower WMH volume with lower WM CBF, smoking with higher WM sCoV, and higher SBP with lower GM sCoV.

Conclusions

These findings suggest that cerebral haemodynamics differ between ethnic groups in midlife. Although no interaction with ethnicity was found in the associations of CV risk factors, the observed differences in CBF and sCoV highlight the need to further explore how ethnic-specific risk profiles may contribute to cerebrovascular pathology over time.
{"title":"Mid-life association between cardiovascular risk factors and cerebral blood flow in a multi-ethnic population","authors":"Esther M.C. Vriend ,&nbsp;Mathijs B.J. Dijsselhof ,&nbsp;Thomas A. Bouwmeester ,&nbsp;Oscar H. Franco ,&nbsp;Henrike Galenkamp ,&nbsp;Didier Collard ,&nbsp;Aart J. Nederveen ,&nbsp;Bert-Jan H. van den Born ,&nbsp;Henk J.M.M. Mutsaerts","doi":"10.1016/j.cccb.2025.100384","DOIUrl":"10.1016/j.cccb.2025.100384","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular (CV) risk factors are associated with cerebrovascular damage and cognitive decline in late-life. However, it is unknown how different ethnic CV risk profiles relate to cerebral haemodynamics in mid-life. We aimed to investigate associations of CV risk factors with cerebral haemodynamics at two timepoints and examine the impact of ethnicity on these measures.</div></div><div><h3>Methods</h3><div>From the HELIUS study (53.0 years, 44.8 % female), participants of Dutch (<em>n</em> = 236), Moroccan (<em>n</em> = 122), or South-Asian Surinamese (<em>n</em> = 173) descent were included. Cerebral blood flow (CBF) and its spatial coefficient of variation (sCoV, an ASL-label arrival measure of macrovascular efficiency) were obtained in grey (GM) and white matter (WM). CV risk factors were assessed 8.4 years [7.4–9.5] (first visit) and 2.2 years [1.8–2.6] (second visit) prior to MRI. Associations of CV risk factors, WM hyperintensities (WMH), and carotid plaques with cerebral haemodynamics were investigated using linear regressions.</div></div><div><h3>Results</h3><div>CBF and sCoV differed per ethnicity. Only at the second visit associations were found, without an interaction with ethnicity; history of CV disease with lower GM CBF and higher WM sCoV, higher total cholesterol and lower WMH volume with lower WM CBF, smoking with higher WM sCoV, and higher SBP with lower GM sCoV.</div></div><div><h3>Conclusions</h3><div>These findings suggest that cerebral haemodynamics differ between ethnic groups in midlife. Although no interaction with ethnicity was found in the associations of CV risk factors, the observed differences in CBF and sCoV highlight the need to further explore how ethnic-specific risk profiles may contribute to cerebrovascular pathology over time.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100384"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800101","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}
引用次数: 0
Where in the brain is human intelligence?✰ 人类的智力在大脑的什么地方?
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2024.100374
Lars Nyberg
We still know relatively little about how the human brain supports intelligence. I this personal view I argue that adopting the framework of neurocognitive component processes (NCP) might advance the current state of knowledge. Integration of information processing across distributed brain regions is proposed as a potential NCP, and some possible clinical implications of adopting the NCP framework are outlined.
对于人脑如何支持智力,我们仍然知之甚少。根据我的个人观点,我认为采用神经认知成分过程(NCP)的框架可能会推进当前的知识状态。跨分布脑区的信息处理整合被认为是一种潜在的NCP,并概述了采用NCP框架的一些可能的临床意义。
{"title":"Where in the brain is human intelligence?✰","authors":"Lars Nyberg","doi":"10.1016/j.cccb.2024.100374","DOIUrl":"10.1016/j.cccb.2024.100374","url":null,"abstract":"<div><div>We still know relatively little about how the human brain supports intelligence. I this personal view I argue that adopting the framework of neurocognitive component processes (NCP) might advance the current state of knowledge. Integration of information processing across distributed brain regions is proposed as a potential NCP, and some possible clinical implications of adopting the NCP framework are outlined.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100374"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933821","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}
引用次数: 0
Electroacupuncture protects against cerebral ischemia-reperfusion injury via regulating P2×7R expression
IF 1.9 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.cccb.2025.100379
Sijia Chen , Ye Zhu , Feihong Lin , Hanming Jiang , Haipeng Liu , Shan Li , Xuliang Huang , Yunchang Mo , Junlu Wang , Qinxue Dai

Background

Ischemic stroke is a serious clinical condition that is challenging to cure; therefore, slowing down the depletion of ATP is crucial to enhancing the tolerance of ischemic tissue through preconditioning. Electroacupuncture (EA) preconditioning induces tolerance to cerebral ischemia; however, the underlying mechanism remains unclear.

Objective

The P2×7 receptor (P2×7R) mediates the stimulation of microglial cells and is involved in the development of cerebral ischemia-reperfusion (I/R) damage. We hypothesized that the protective effect of EA preconditioning is associated with the downregulation of P2×7R expression.

Methods

We performed EA at the "Baihui" and "Fengfu" for 30 min before establishing a rat model of cerebral I/R induced based on the middle cerebral artery occlusion model (MCAO). MCAO rats were administered a ventricular injection of 2 '(3′)-O-(4-benzoyl) adenosine triphosphate (BzATP), a P2×7R agonist, 30 min before EA. Neurologic scoring, infarction volume, and expression of cytokines, Bcl-2 and Bax, Iba1, P2×7R, p38, and phosphorylated p38 (p-p38) in ischemia penumbra were detected 24 h after cerebral I/R.

Results

EA preconditioning ameliorated neurologic scoring, decreased infarction volume, and neuronal injury, and decreased cytokine release, while BzATP exacerbated cerebral I/R damage and inflammation events, unlike the favorable efficacy of EA. EA inhibited the expression of Iba-1, P2×7R, and p-p38/p38 in the ischemic penumbra, whereas BzATP reversed this effect.

Conclusions

EA could induce cerebral tolerance to I/R damage by suppressing P2×7R expression and release of inflammatory factors.
{"title":"Electroacupuncture protects against cerebral ischemia-reperfusion injury via regulating P2×7R expression","authors":"Sijia Chen ,&nbsp;Ye Zhu ,&nbsp;Feihong Lin ,&nbsp;Hanming Jiang ,&nbsp;Haipeng Liu ,&nbsp;Shan Li ,&nbsp;Xuliang Huang ,&nbsp;Yunchang Mo ,&nbsp;Junlu Wang ,&nbsp;Qinxue Dai","doi":"10.1016/j.cccb.2025.100379","DOIUrl":"10.1016/j.cccb.2025.100379","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke is a serious clinical condition that is challenging to cure; therefore, slowing down the depletion of ATP is crucial to enhancing the tolerance of ischemic tissue through preconditioning. Electroacupuncture (EA) preconditioning induces tolerance to cerebral ischemia; however, the underlying mechanism remains unclear.</div></div><div><h3>Objective</h3><div>The P2×7 receptor (P2×7R) mediates the stimulation of microglial cells and is involved in the development of cerebral ischemia-reperfusion (I/R) damage. We hypothesized that the protective effect of EA preconditioning is associated with the downregulation of P2×7R expression.</div></div><div><h3>Methods</h3><div>We performed EA at the \"Baihui\" and \"Fengfu\" for 30 min before establishing a rat model of cerebral I/R induced based on the middle cerebral artery occlusion model (MCAO). MCAO rats were administered a ventricular injection of 2 '(3′)-O-(4-benzoyl) adenosine triphosphate (BzATP), a P2×7R agonist, 30 min before EA. Neurologic scoring, infarction volume, and expression of cytokines, Bcl-2 and Bax, Iba1, P2×7R, p38, and phosphorylated p38 (p-p38) in ischemia penumbra were detected 24 h after cerebral I/R.</div></div><div><h3>Results</h3><div>EA preconditioning ameliorated neurologic scoring, decreased infarction volume, and neuronal injury, and decreased cytokine release, while BzATP exacerbated cerebral I/R damage and inflammation events, unlike the favorable efficacy of EA. EA inhibited the expression of Iba-1, P2×7R, and p-p38/p38 in the ischemic penumbra, whereas BzATP reversed this effect.</div></div><div><h3>Conclusions</h3><div>EA could induce cerebral tolerance to I/R damage by suppressing P2×7R expression and release of inflammatory factors.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100379"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478643","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}
引用次数: 0
期刊
Cerebral circulation - cognition and behavior
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