scholarly journals The brain health index: Towards a combined measure of neurovascular and neurodegenerative structural brain injury

2018 ◽  
Vol 13 (8) ◽  
pp. 849-856 ◽  
Author(s):  
David Alexander Dickie ◽  
Maria del C Valdés Hernández ◽  
Stephen D Makin ◽  
Julie Staals ◽  
Stewart J Wiseman ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Health Index ◽  
Brain Health ◽  
Vessel Disease ◽  
Standard Beta ◽  
The Brain ◽  
Healthy Participants

Background A structural magnetic resonance imaging measure of combined neurovascular and neurodegenerative burden may be useful as these features often coexist in older people, stroke and dementia. Aim We aimed to develop a new automated approach for quantifying visible brain injury from small vessel disease and brain atrophy in a single measure, the brain health index. Materials and methods We computed brain health index in N = 288 participants using voxel-based Gaussian mixture model cluster analysis of T1, T2, T2*, and FLAIR magnetic resonance imaging. We tested brain health index against a validated total small vessel disease visual score and white matter hyperintensity volumes in two patient groups (minor stroke, N = 157; lupus, N = 51) and against measures of brain atrophy in healthy participants (N = 80) using multiple regression. We evaluated associations with Addenbrooke’s Cognitive Exam Revised in patients and with reaction time in healthy participants. Results The brain health index (standard beta = 0.20–0.59, P < 0.05) was significantly and more strongly associated with Addenbrooke’s Cognitive Exam Revised, including at one year follow-up, than white matter hyperintensity volume (standard beta = 0.04–0.08, P > 0.05) and small vessel disease score (standard beta = 0.02–0.27, P > 0.05) alone in both patient groups. Further, the brain health index (standard beta = 0.57–0.59, P < 0.05) was more strongly associated with reaction time than measures of brain atrophy alone (standard beta = 0.04–0.13, P > 0.05) in healthy participants. Conclusions The brain health index is a new image analysis approach that may usefully capture combined visible brain damage in large-scale studies of ageing, neurovascular and neurodegenerative disease.

scholarly journals Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 994
Author(s):  
Natasha Ting Lee ◽  
Lin Kooi Ong ◽  
Prajwal Gyawali ◽  
Che Mohd Nasril Che Mohd Nassir ◽  
Muzaimi Mustapha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Small Vessel Disease ◽  
Ischemia Reperfusion ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Purinergic Signalling ◽  
Vessel Disease ◽  
The Brain

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.

Abstract P626: Periodontal Disease is Independently Associated With Cerebral Small Vessel Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Forrest Lowe ◽  
Souvik Sen ◽  
Hamdi S Adam ◽  
Ryan Demmer ◽  
Bruce A Wasserman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Periodontal Disease ◽  
Small Vessel Disease ◽  
Multinomial Logistic Regression ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Periodontal Health ◽  
Vessel Disease ◽  
The Relationship

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.

Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013077
Author(s):  
Corey W Bown ◽  
Roxana O Carare ◽  
Matthew S Schrag ◽  
Angela L Jefferson
Keyword(s):  
Fluid Transport ◽  
Small Vessel Disease ◽  
Treatment Strategies ◽  
Small Vessel ◽  
Aging Brain ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Clinical Consequences ◽  
The Brain

Perivascular spaces (PVS) are fluid filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on magnetic resonance imaging. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as two possible mechanisms that drive ePVS formation. In this review, we describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the two most prominent theoretical views and review ePVS associations with other common small vessel disease markers. As ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer’s disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Dorothee Schoemaker ◽  
Yesica Zuluaga ◽  
Lina Velilla ◽  
Carolina Ospina ◽  
Francisco Lopera ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Structural Mri ◽  
Vascular Cognitive Impairment ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Perivascular Spaces ◽  
Cerebrovascular Injury ◽  
Vessel Disease ◽  
History Of

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.

scholarly journals Response to "Carotid Flow Augmentation as a Risk for Small Vessel Disease of the Brain"

2010 ◽  
Vol 23 (9) ◽  
pp. 933-933
Author(s):  
K. Kohara ◽  
N. Ochi ◽  
Y. Tabara ◽  
T. Miki
Keyword(s):  
Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
The Brain ◽  
Carotid Flow

scholarly journals Risk factors for small-vessel disease revealed by magnetic resonance imaging of the brain.

Nosotchu ◽  
1996 ◽  
Vol 18 (1) ◽  
pp. 10-18
Author(s):  
Tatsuo Kohriyama ◽  
Shinya Yamaguchi ◽  
Eiji Tanaka ◽  
Yasuhiro Yamamura ◽  
Shigenobu Nakamura
Keyword(s):  
Magnetic Resonance Imaging ◽  
Risk Factors ◽  
Magnetic Resonance ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Resonance Imaging ◽  
Vessel Disease ◽  
The Brain

scholarly journals Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease

2015 ◽  
Vol 112 (7) ◽  
pp. E796-E805 ◽  
Author(s):  
Fabrice Dabertrand ◽  
Christel Krøigaard ◽  
Adrian D. Bonev ◽  
Emmanuel Cognat ◽  
Thomas Dalsgaard ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Genetic Model ◽  
Small Vessel Disease ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
Small Vessel ◽  
Pial Arteries ◽  
Vessel Disease ◽  
Myogenic Responses ◽  
The Brain

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by dominant mutations in the NOTCH3 receptor in vascular smooth muscle, is a genetic paradigm of small vessel disease (SVD) of the brain. Recent studies using transgenic (Tg)Notch3R169C mice, a genetic model of CADASIL, revealed functional defects in cerebral (pial) arteries on the surface of the brain at an early stage of disease progression. Here, using parenchymal arterioles (PAs) from within the brain, we determined the molecular mechanism underlying the early functional deficits associated with this Notch3 mutation. At physiological pressure (40 mmHg), smooth muscle membrane potential depolarization and constriction to pressure (myogenic tone) were blunted in PAs from TgNotch3R169C mice. This effect was associated with an ∼60% increase in the number of voltage-gated potassium (KV) channels, which oppose pressure-induced depolarization. Inhibition of KV1 channels with 4-aminopyridine (4-AP) or treatment with the epidermal growth factor receptor agonist heparin-binding EGF (HB-EGF), which promotes KV1 channel endocytosis, reduced KV current density and restored myogenic responses in PAs from TgNotch3R169C mice, whereas pharmacological inhibition of other major vasodilatory influences had no effect. KV1 currents and myogenic responses were similarly altered in pial arteries from TgNotch3R169C mice, but not in mesenteric arteries. Interestingly, HB-EGF had no effect on mesenteric arteries, suggesting a possible mechanistic basis for the exclusive cerebrovascular manifestation of CADASIL. Collectively, our results indicate that increasing the number of KV1 channels in cerebral smooth muscle produces a mutant vascular phenotype akin to a channelopathy in a genetic model of SVD.

Small vessel disease

2020 ◽  
pp. 203-212
Author(s):  
Fergus N Doubal ◽  
Anna Poggesi ◽  
Leonardo Pantoni ◽  
Joanna M Wardlaw
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Intrinsic Disorder ◽  
Small Vessel ◽  
Imaging Features ◽  
World Region ◽  
Vessel Disease ◽  
Cerebral Arterioles ◽  
The Brain ◽  
Review Current

‘Small vessel disease’ describes a combination of neuroradiological and clinical features that are due to an intrinsic disorder of the small cerebral arterioles, capillaries, and venules in varying proportions. It is very common, usually sporadic, although rare monogenic forms are well described. The commonest presentations are with stroke or cognitive impairment. The cause of the small vessel abnormalities in the sporadic form is not well understood and the brain damage is generally attributed to ischaemia secondary to the vessel abnormality. However, evidence for altered microvessel function and blood brain barrier failure is accumulating. The commonest risk factors are increasing age, hypertension, smoking, and diabetes, but environmental and lifestyle factors are also important although poorly understood. Whether the imaging features or incidence of small vessel-related stroke or dementia vary by world region is unknown. We review current knowledge on presentation, aetiology, incidence, and prevalence of sporadic small vessel disease.

scholarly journals Contributions of Aging to Cerebral Small Vessel Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 275-295 ◽  
Author(s):  
T. Michael De Silva ◽  
Frank M. Faraci
Keyword(s):  
Recent Progress ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Brain Health ◽  
Vessel Disease ◽  
Age Related ◽  
The Face ◽  
Basic Biology ◽  
The Impact

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Underlying phenotypes and mechanisms are multifactorial, with no specific treatments at this time. Despite consequences that are already considerable, the impact of SVD is predicted to increase substantially with the growing aging population. In the face of this health challenge, the basic biology, pathogenesis, and determinants of SVD are poorly defined. This review summarizes recent progress and concepts in this area, highlighting key findings and some major unanswered questions. We focus on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.

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