Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.

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Automated detection of cerebral microbleeds on T2*-weighted MRI

Scientific Reports ◽

10.1038/s41598-021-83607-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anthony G. Chesebro ◽

Erica Amarante ◽

Patrick J. Lao ◽

Irene B. Meier ◽

Richard Mayeux ◽

...

Keyword(s):

Large Scale ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Amyloid Angiopathy ◽

Cross Sectional ◽

Visual Rating ◽

Anatomical Localization ◽

Mri Sequences ◽

Magnetic Resonance Imaging Mri ◽

Detection Instrument

AbstractCerebral microbleeds, observed as small, spherical hypointense regions on gradient echo (GRE) or susceptibility weighted (SWI) magnetic resonance imaging (MRI) sequences, reflect small hemorrhagic infarcts, and are associated with conditions such as vascular dementia, small vessel disease, cerebral amyloid angiopathy, and Alzheimer’s disease. The current gold standard for detecting and rating cerebral microbleeds in a research context is visual inspection by trained raters, a process that is both time consuming and subject to poor reliability. We present here a novel method to automate microbleed detection on GRE and SWI images. We demonstrate in a community-based cohort of older adults that the method is highly sensitive (greater than 92% of all microbleeds accurately detected) across both modalities, with reasonable precision (fewer than 20 and 10 false positives per scan on GRE and SWI, respectively). We also demonstrate that the algorithm can be used to identify microbleeds over longitudinal scans with a higher level of sensitivity than visual ratings (50% of longitudinal microbleeds correctly labeled by the algorithm, while manual ratings was 30% or lower). Further, the algorithm identifies the anatomical localization of microbleeds based on brain atlases, and greatly reduces time spent completing visual ratings (43% reduction in visual rating time). Our automatic microbleed detection instrument is ideal for implementation in large-scale studies that include cross-sectional and longitudinal scanning, as well as being capable of performing well across multiple commonly used MRI modalities.

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Experimental Rodent Models of Vascular Dementia: A Systematic Review

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666210108123438 ◽

2021 ◽

Vol 19 ◽

Author(s):

Nidhi Tiwari ◽

Jyoti Upadhyay ◽

Mohd Nazam Ansari ◽

Syed Shadab Raza ◽

Wasim Ahmad ◽

...

Keyword(s):

Vascular Dementia ◽

Small Vessel Disease ◽

Current Knowledge ◽

Vascular Cognitive Impairment ◽

Experimental Models ◽

New Drugs ◽

Amyloid Angiopathy ◽

Vessel Disease ◽

The Brain ◽

Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

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Structural MRI

International Psychogeriatrics ◽

10.1017/s1041610211000913 ◽

2011 ◽

Vol 23 (S2) ◽

pp. S13-S24 ◽

Cited By ~ 19

Author(s):

Mike P. Wattjes

Keyword(s):

Rating Scales ◽

Structural Mri ◽

Vascular Damage ◽

Cortical Atrophy ◽

Amyloid Angiopathy ◽

Memory Clinic ◽

Visual Rating ◽

Diagnosis Of Dementia ◽

Magnetic Resonance Imaging Mri ◽

Diagnostic Work

ABSTRACTClinical neuroimaging is increasingly being used in the diagnosis of neurodegenerative diseases and has become one of the most important paraclinical tools in the diagnosis of dementia. According to current guidelines, neuroimaging, preferably magnetic resonance imaging (MRI), should be performed at least once during the diagnostic work-up of patients with suspected or definite dementia. MRI is helpful in identifying or excluding potentially treatable causes of dementia; however, these account only for a small proportion of dementias. In addition, MRI is able to support the clinical diagnosis in a memory clinic setting by identifying certain patterns of atrophy and vascular damage. Visual rating scales are well-established methods in the clinical routine for the assessment and quantification of regional/global cortical atrophy, hippocampal atrophy and vascular damage. In addition, MRI is able to detect certain aspects of pathology associated with dementia, such as cerebral microbleeds which are related to cerebral amyloid angiopathy and Alzheimer pathology. This review paper aims to give an overview of the application of structural MRI in the diagnostic procedure for memory clinic patients in terms of excluding and supporting the diagnosis of various diseases associated with dementia.

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Measurements of lenticulostriate arteries using 7T MRI: new imaging markers for subcortical vascular dementia

Journal of the Neurological Sciences ◽

10.1016/j.jns.2012.05.032 ◽

2012 ◽

Vol 322 (1-2) ◽

pp. 200-205 ◽

Cited By ~ 19

Author(s):

Sang Won Seo ◽

Chang-Ki Kang ◽

Sook Hui Kim ◽

Doo Sang Yoon ◽

Wei Liao ◽

...

Keyword(s):

Vascular Dementia ◽

Lenticulostriate Arteries ◽

Subcortical Vascular Dementia ◽

Imaging Markers

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Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study

Current Alzheimer Research ◽

10.2174/1567205018666210820125543 ◽

2021 ◽

Vol 18 ◽

Author(s):

Bibek Gyanwali ◽

Benedict Lui ◽

Chuen Seng Tang ◽

Eddie Jun Yi Chong ◽

Henri Vrooman ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

Future Research ◽

Amyloid Angiopathy ◽

Linear Regression Models ◽

Interaction Factor

Background: Cerebral small vessel disease (SVD); lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hyper- tensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive de- cline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuro- psychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed simi- lar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cogni- tion, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

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Striped occipital cortex and intragyral hemorrhage: Novel magnetic resonance imaging markers for cerebral amyloid angiopathy

International Journal of Stroke ◽

10.1177/1747493021991961 ◽

2021 ◽

pp. 174749302199196

Author(s):

EA Koemans ◽

S Voigt ◽

I Rasing ◽

WMT Jolink ◽

TW van Harten ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Occipital Cortex ◽

7 Tesla ◽

Amyloid Angiopathy ◽

Resonance Imaging ◽

Imaging Markers ◽

Cerebral Amyloid

Background and aim To investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH). Methods We performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. Results We included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging. Conclusion Whereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

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Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Stroke ◽

10.1161/strokeaha.119.028487 ◽

2020 ◽

Vol 51 (12) ◽

pp. 3600-3607 ◽

Cited By ~ 1

Author(s):

Young Hee Jung ◽

Hyemin Jang ◽

Seong Beom Park ◽

Yeong Sim Choe ◽

Yuhyun Park ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Disease Burden ◽

Dentate Nucleus ◽

Small Vessel Disease ◽

Amyloid Β ◽

Cerebral Microbleeds ◽

Amyloid Angiopathy ◽

Positron Emission ◽

Aβ Amyloid ◽

Cerebral Amyloid

Background and Purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P <0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P =0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P =0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P =0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P =0.041) than the dentate group. Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

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Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds

Neurology ◽

10.1212/wnl.0000000000004259 ◽

2017 ◽

Vol 89 (8) ◽

pp. 820-829 ◽

Cited By ~ 71

Author(s):

Andreas Charidimou ◽

Toshio Imaizumi ◽

Solene Moulin ◽

Alexandro Biffi ◽

Neshika Samarasekera ◽

...

Keyword(s):

Small Vessel Disease ◽

Meta Analysis ◽

Brain Mri ◽

Recurrence Risk ◽

Cerebral Microbleeds ◽

Small Vessel ◽

Amyloid Angiopathy ◽

Random Effects Models ◽

Pooled Data ◽

Vessel Disease

Objective:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity).Methods:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models.Results:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years): OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.Conclusions:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.

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Guidelines for Brain Imaging in Vascular Dementia Clinical Trials

International Psychogeriatrics ◽

10.1017/s1041610203009323 ◽

2003 ◽

Vol 15 (S1) ◽

pp. 273-276 ◽

Cited By ~ 3

Author(s):

Frederik Barkhof

Keyword(s):

Clinical Trials ◽

Vascular Dementia ◽

Rating Scales ◽

Imaging Modality ◽

White Matter Lesions ◽

Gradient Echo ◽

Visual Rating ◽

Dementia Patients ◽

Natural Progression ◽

Central Data

Imaging should be included in the workup of dementia patients and is mandatory for the diagnosis of vascular dementia (VaD). MRI is the preferred imaging modality and should include axial T2 and FLAIR, preferably accompanied by a 3D T1-weighted sequence in clinical trials to determine white-matter lesions, infarcts, lacunes, and atrophy. Gradient echo images are needed for microbleeds. Diagnostic criteria should be operationalized and validated visual rating scales are available. In clinical trials, standardized acquisition protocols and central data analysis are mandatory. More work is needed to determine the natural progression in VaD and the possible use of MRI-based outcome measures.

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Hypertensive Arteriopathy and Cerebral Amyloid Angiopathy in Patients with Cognitive Decline and Mixed Cerebral Microbleeds

Journal of Alzheimer s Disease ◽

10.3233/jad-200992 ◽

2020 ◽

Vol 78 (4) ◽

pp. 1765-1774

Author(s):

Yuichiro Ii ◽

Hidehiro Ishikawa ◽

Hirofumi Matsuyama ◽

Akihiro Shindo ◽

Keita Matsuura ◽

...

Keyword(s):

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Cerebral Microbleeds ◽

White Matter Hyperintensity ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Age Related ◽

Cerebral Amyloid ◽

Occipital Lobes

Background: Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies. Objective: We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs. Methods: Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale. Results: The two scores were positively correlated (ρ= 0.449, p < 0.001). The prevalence of lobar dominant CMB distribution (p < 0.001) and lacunes in the centrum semiovale (p < 0.001) and the severity of WMH in the parieto-occipital lobes (p = 0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH. Conclusion: Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.

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