Abstract WP451: Cognitive Impairment in Cardiac Disease - Neuroimaging Associations

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jane Cannon ◽  
Mark Findlay ◽  
Krishna Dani ◽  
Jesse Dawson ◽  
David A Dickie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cardiac Disease ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Perivascular Spaces ◽  
Intracranial Volume ◽  
Brain Volumes ◽  
Multivariable Models ◽  
Cardiac Status

Introduction: Atrial fibrillation (AF) and heart failure (HF) are associated with cognitive impairment. We used neuroimaging to describe if this association is explained by cardioembolism or other mechanisms. Methods: We included adults with HF (ejection fraction<45%) and AF but no stroke history. Healthy volunteer controls were matched, 1:2 ratio. Participants were assessed with Repeatable Battery for the Assessment of Neurospychological Status (RBANS), Hospital Anxiety and Depression Score (HADS) and 3-T brain MRI. Scans were graded for:infarct, enlarged perivascular spaces, microbleeds, global and regional (hippocampal) atrophy with consensus scoring by four raters using validated, ordinal assessment scales. Brain volumes were semi-automatically acquired using cluster analysis of T1-weighted and FLAIR voxel intensities and diffeomorphic atlas-based segmentation. CSF, hippocampal and white matter volumes were corrected for intracranial volume. We described univariable differences between groups and then created multivariable models where cardiac status was the dependent variable, RBANS and MRI data were the predictors. Results: Of 50 participants, AF-HF (n=34) had poorer RBANS (MD:16.9, SE:3.44; p<0.001). Differences were independent of education and HADS. Infarcts and ordinal markers of atrophy were significantly different between groups, SVD markers were increased in AF-HF but did not reach significance. Quantitative measures of white matter differed between groups but measures of atrophy did not.(Table) On multivariable models, no imaging feature was independently associated with cardiac status. Discussion: The association between cognitive impairment and cardiac disease may not be solely driven by occult cardioembolism; small vessel disease and other, neuroimaging independent, factors also interact. Differences between ordinal scales and quantitative scores suggest that future studies should use robust volumetric analyses.

scholarly journals Arterial stiffness and dementia pathology

Neurology ◽  
2018 ◽  
Vol 90 (14) ◽  
pp. e1248-e1256 ◽  
Author(s):  
Timothy M. Hughes ◽  
Lynne E. Wagenknecht ◽  
Suzanne Craft ◽  
Akiva Mintz ◽  
Gerardo Heiss ◽  
...  
Keyword(s):  
White Matter ◽  
Arterial Stiffness ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Volume Ratio ◽  
Cognitive Testing ◽  
White Matter Hyperintensity ◽  
Cross Sectional ◽  
Brain Volumes ◽  
Atherosclerosis Risk In Communities

ObjectiveArterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts.MethodsThe Atherosclerosis Risk in Communities (ARIC)–Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition.ResultsAmong the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01–1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease–susceptible regions (in mm3, β = −1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2–2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1–2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status.ConclusionsArterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.

Abstract 043: Leisure-Time Physical Activity in Adulthood and Region of Interest (ROI) Brain Volumes: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Priya Palta ◽  
A R Sharrett ◽  
Kelly R Evenson ◽  
Clifford R Jack ◽  
Pamela L Lutsey ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Impairment ◽  
Life Table ◽  
Brain Mri ◽  
Late Life ◽  
Intracranial Volume ◽  
Reverse Causality ◽  
Cross Sectional ◽  
Brain Volumes ◽  
Age Related

Introduction: Several studies report late-life physical activity (PA) to be associated with less brain atrophy. Associations of PA and subclinical brain markers evaluated at older ages may be subject to reverse causality due to comorbidity, age-related changes in lifestyle, or incipient cognitive impairment. Therefore, we aimed to compare late-life cross-sectional estimates of PA and ROI brain volumes to those using prospective PA measures from mid- to late-life. Methods: Participants (n=1549, mean age: 75, 39% male, 20% Black) with repeat assessments of PA from visit 1 (1987-1989) and a brain magnetic resonance imaging (MRI) in 2011-2013 were included. Total volume of PA in metabolic equivalent-min/week was estimated using the Baecke Physical Activity Questionnaire and classified as no, low, middle or high at each visit. Based on visit 1 and 3 (1993-1995) PA assessments, a subset of participants (n=663) were further categorized as habitually inactive or having habitually low, middle, or high PA in mid-life. Brain MRI using 3D-1.5T equipment quantified ROI volumes following a standardized protocol. Weighted linear regression adjusted for intracranial volume, demographics, select cardiovascular risk factors and ApoE4 estimated the standardized difference in ROI volumes. Results: Compared to no PA, high PA was associated with larger ROI brain volumes cross-sectionally in late-life (Table). High mid-life PA was only modestly associated with larger frontal cortical and deep gray matter volumes in late-life (Table). Habitually high PA in mid-life was not associated with less atrophy across brain regions in late-life. Conclusions: Our results do not support a causal interpretation of the cross-sectional associations between PA and brain volumes reported in late-life. Drawing on long-term population-based data, this study provides novel information on the associations of PA across life epochs with brain health, which can inform translational and intervention efforts to reduce age-related cognitive impairment.

Abstract 151: Enlarged Perivascular Spaces in Lacunar Stroke Patients. The Secondary Prevention of Small Subcortical Stroked (SPS3) trial.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Hideki Ohba ◽  
Lesly Pearce ◽  
Gillian Potter ◽  
Oscar Benavente
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Large Cohort ◽  
Common Finding ◽  
Perivascular Spaces ◽  
Lacunar Stroke ◽  
Stroke Patients ◽  
Age Related

Introduction: Enlarge perivascular spaces (EPVS) are a common finding on MRI with little known about their aetiology or clinical significance. Associations of EPVS with white matter hyperintensities (WMH) and cognitive impairment have been reported. We assessed the prevalence of EPVS in the basal ganglia (BG) and centrum semiovale (CS) and associations with vascular risk factors, MRI abnormalities, and cognitive impairment in a large cohort of MRI documented lacunar stroke patients. Methods: All SPS3 participants enrolled in North America (N=1632) were included in the cohort. MRIs were obtained at the time of index stroke. We graded severity of EPVS on T2 in each of the right and left BG and CS as: <10, 11-20, or 20+. We assessed relationships between maximum (max) BG and CS scores and patient demographics, number of subcortical infarcts, WMH, and cognitive impairment using chi-square tests and ANOVA. Logistic regression was used to identify independent associations between max score in the BG or CS (<10 vs. 11+ points) and these factors. Results: Of the 1632 MRIs, 1172 had T2-imaging available. EPVS was symmetrical in right and left sides of BG and of CS so max score in each area were used for analyses. In 42% of BG and 69% of CS, the max number of unilateral EPVS was ≥11. Patients with more EPVS in the BG were older (mean 59 vs. 63 vs. 70 years, p < 0.001), had hypertension (75% vs. 84% vs. 86% p < 0.001), and lower eGFR (mean 83 vs. 80 vs. 74 ml/min/1.73m 2 , p = 0.006). More EPVS in the BG were associated with WMH severity as measured by Age Related White Matter Changes total score (median 3 vs. 6 vs. 8, p < 0.001). Patients with more EPVS in the BG more often had multiple infarcts (11% vs. 19% vs. 29%, p<0.001). All findings were similar in the CS. Age (OR 1.9 per each 10 years, 95% CI 1.7-2.1), history of hypertension (OR 1.7, 95% CI 1.2-2.3) and multiple infarcts (OR 2.4, 95% CI 1.7-3.4) were independently associated with a maximum unilateral EPVS score of 2+ in the BG. Mild cognitive impairment was not associated with EPVS in BG (p=0.3) or CS (p=0.5). Conclusions: In this well-defined large cohort of lacunar stroke patients, BG EPVS were associated with age, hypertension and multiple infarcts. These findings suggest that BG EPVS share similar risk factors with lacunar stroke and may be a marker for small vessel disease. Unexpectedly, EPVS were not associated with cognitive impairment.

scholarly journals Perivascular spaces in the centrum semiovale at the beginning of the 8th decade of life: effect on cognition and associations with mineral deposition

2019 ◽  
Vol 14 (5) ◽  
pp. 1865-1875 ◽  
Author(s):  
Maria del C. Valdés Hernández ◽  
Lucia Ballerini ◽  
Andreas Glatz ◽  
Susana Muñoz Maniega ◽  
Alan J. Gow ◽  
...  
Keyword(s):  
Linear Models ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Community Dwelling ◽  
Cognitive Testing ◽  
White Matter Hyperintensity ◽  
Perivascular Spaces ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Centrum Semiovale

Abstract Brain iron deposits (IDs) are indicative of microvessel dysfunction which may predispose to small vessel disease (SVD) brain damage and worsen cognition later in life. Visible perivascular spaces in the centrum semiovale (CSO-PVS) are SVD features linked with microvessel dysfunction. We examined possible associations of CSO-PVS volume and count with brain IDs and cognitive abilities in 700 community-dwelling individuals from the Lothian Birth Cohort 1936 who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years. Brain IDs were assessed automatically followed by manual editing. PVS were automatically assessed in the centrum semiovale and deep corona radiata supraventricular. General factors of overall cognitive function (g), processing speed (g-speed) and memory (g-memory) were used in the analyses. Median (IQR) volumes of IDs and CSO-PVS expressed as a percentage of intracranial volume were 0.0021 (0.011) and 0.22 (0.13)% respectively. Median count of CSO-PVS was 410 (IQR = 201). Total volumes of CSO-PVS and ID, adjusted for head size, were correlated (Spearman ρ = 0.13, p < 0.001). CSO-PVS volume, despite being correlated with all three cognitive measures, was only associated with g-memory (B = -114.5, SE = 48.35, p = 0.018) in general linear models, adjusting for age, sex, vascular risk factors, childhood intelligence and white matter hyperintensity volume. The interaction of CSO-PVS count with diabetes (B = -0.0019, SE = 0.00093, p = 0.041) and volume with age (B = 1.57, SE = 0.67, p = 0.019) were also associated with g-memory. Linear regression models did not replicate these associations. Therefore, it does not seem that CSO-PVS burden is directly associated with general cognitive ability in older age.

scholarly journals Enlarged perivascular spaces and cognitive impairment after stroke and transient ischemic attack

2016 ◽  
Vol 13 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Francesco Arba ◽  
Terence J Quinn ◽  
Graeme J Hankey ◽  
Kennedy R Lees ◽  
Joanna M Wardlaw ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
One Year

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03–2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

Abstract T P234: Multiparametric Assessment of Longitudinal Changes in Tissue Microstructure in Normal and Abnormal Brain Tissue in Patients with Small Vessel Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Maria D Valdes-Hernandez ◽  
Paul A Armitage ◽  
Eleni Sakka ◽  
Susana Munoz Maniega ◽  
Natalie A Royle ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Tissue Loss ◽  
Minor Stroke ◽  
Normal Brain ◽  
Limited Information ◽  
Time Points

Background: Volume measures of normal brain tissue and white matter hyperintensities (WMH) between two time points gives limited information about the complex dynamics of tissue change. We evaluated two quantitative parameters that characterise the microstructure of normal-appearing white matter (NAWM), deep grey matter (DGM) and WMH on brain images obtained at presentation with minor stroke and at 1 year to investigate the microstructural changes. Methods: From 182 brain MRI datasets of patients with minor stroke obtained at baseline and 1 year, we extracted the WMH, DGM and NAWM, and separated WMH into less-intense and intense WMH, using validated semi-automatic methods and validated criteria. We registered the binary structural masks to diffusion space and performed a voxel-wise subtraction of the combined masks at both time points. Then we measured fractional anisotropy (FA) and mean diffusivity (MD)(valuex10 -9 m 2 /s) in each tissue mask at baseline and 1 year. Results: WMH volume median increase was 1.4ml (IQR 6.98) mainly due to changes in less-intense WMH: 0.94ml (7.13). WMH that were visible at both time points, ie damage that remained after a year, had the lowest FA= 0.21(0.06) and highest MD=1.05(0.12) at baseline, and were mainly intense WMH at baseline (FA=0.12(0.03), MD=1.55(0.27)). WMH seen only at follow-up, ie that were NAWM at baseline, had the highest FA=0.30(0.06) and lowest MD=0.85 (0.06) at baseline. WMH that were observed only at baseline had intermediate FA=0.26(0.08) and MD=0.90(0.10). NAWM FA=0.26(0.03), MD=0.78(0.04) and DGM FA=0.23(0.03), MD=0.79(0.06) did not change between time points. Conclusions: WMH at baseline can partially evolve to normal-appearing tissues, remain or precede tissue loss. Differentiation between severe and subtle damage and spatial analysis are necessary to characterise the dynamic of WMH evolution.

Fish Intake and MRI Burden of Cerebrovascular Disease in Older Adults

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012916
Author(s):  
Aline Thomas ◽  
Fabrice Crivello ◽  
Bernard Mazoyer ◽  
Stephanie Debette ◽  
Christophe Tzourio ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Cerebrovascular Disease ◽  
Brain Mri ◽  
Large Population ◽  
Population Based ◽  
Fish Intake ◽  
Mixed Data ◽  
Perivascular Spaces ◽  
Intracranial Volume ◽  
Cross Sectional

Background and Objective:Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers.Methods:This cross-sectional analysis included participants from the Three-City Dijon population-based cohort (aged ≥65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions.Results:In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish <1 per week, those consuming fish 2-3 and ≥4 times per week had a β = -0.19 (95% CI, -0.37; -0.01) and β = -0.30 (-0.57; -0.03) lower indicator of CVD burden, respectively (P trend <0.001). We found evidence of effect modification by age, so that the association of fish to CVD was stronger in younger participants (65-69 years) and not significant in participants aged ≥75 years. For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in opposite direction) to the effect of hypertension.Discussion:In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease.Classification of Evidence:This study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD at MRI.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

scholarly journals Neuroimaging abnormalities in patients with Cowden syndrome

2018 ◽  
Vol 8 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Radhika Dhamija ◽  
Steven M. Weindling ◽  
Alyx B. Porter ◽  
Leland S. Hu ◽  
Christopher P. Wood ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Mri ◽  
Cowden Syndrome ◽  
Perivascular Spaces ◽  
Developmental Venous Anomaly ◽  
Cortical Malformation ◽  
Cavernous Malformations ◽  
Clinical Criteria ◽  
Signal Abnormality ◽  
Criteria For Diagnosis

BackgroundWe retrospectively reviewed the neuroimaging findings of patients with Cowden syndrome and determined their frequency in a single cohort.MethodsElectronic medical records were queried from January 1999 to January 2017 to identify patients who fit the clinical criteria for diagnosis of Cowden syndrome with or without a documentedPTENmutation. Patients with brain MRI examinations were then identified.ResultsWe retrospectively identified 44 patients with Cowden syndrome, 22 of whom had neuroimaging for review. Eleven (50%) had Lhermitte-Duclos disease, 4 (18.1%) had meningiomas, 13 (59.1%) had at least one developmental venous anomaly, 3 had cavernous malformations, 2 had evidence of dural arteriovenous fistula, 7 had increased white matter signal abnormalities relative to age (31.8%), 4 had prominent perivascular spaces, cerebellar tonsillar ectopia was present in 7 of 21 (33.3%), and 1 had cortical malformation.ConclusionsIt is important to recognize that in addition to Lhermitte-Duclos disease, other intracranial findings such as multiple venous anomalies, meningiomas, greater than expected white matter signal abnormality, prominent perivascular spaces, and cortical malformations may warrant a thorough evaluation for Cowden syndrome in the appropriate clinical setting. We further recommend that this broader spectrum of intracranial abnormalities be considered for addition to the Cowden syndrome diagnostic criteria at the time of next revision.

Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
Matthew Frosch ◽  
Jean-Claude Baron ◽  
Marco Pasi ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Diagnostic Accuracy ◽  
Cerebral Amyloid Angiopathy ◽  
Brain Mri ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Validation Sample ◽  
Temporal Validation ◽  
Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

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