scholarly journals Aβ (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts

Stroke ◽  
2021 ◽  
Author(s):  
A. Kapasi ◽  
S.E. Leurgans ◽  
Z. Arvanitakis ◽  
L.L. Barnes ◽  
D.A. Bennett ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Older People ◽  
Cerebral Amyloid Angiopathy ◽  
Regression Models ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Logistic Regression Models ◽  
Aβ Amyloid ◽  
Tangle Pathology ◽  
Cerebral Amyloid

Background and Purpose: There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aβ (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aβ or tau tangle burden. Methods: Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aβ and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aβ or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts. Results: Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aβ and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aβ (estimate, 0.15; SE=0.07; P =0.02) and tau tangle burden (estimate, 0.13; SE=0.06; P =0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aβ (estimate, 0.27; SE=0.07; P <0.001) and tangle burden (estimate, 0.16; SE=0.06; P =0.005). Conclusions: These findings suggest that in the presence of elevated Aβ or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.

Abstract TP330: Proportion of Intracerebral Haemorrhage Due to Cerebral Amyloid Angiopathy in the East and West

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yusuke Yakushiji ◽  
Jun Tanaka ◽  
Duncan Wilson ◽  
Andreas Charidimou ◽  
Tomoyuki Noguchi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cerebral Amyloid Angiopathy ◽  
Intracerebral Haemorrhage ◽  
East Asian ◽  
Sensitivity Analyses ◽  
Amyloid Angiopathy ◽  
Asian Populations ◽  
Multivariable Logistic Regression ◽  
Cerebral Amyloid ◽  
Centre Origin

Objectives: We investigated whether the proportion of intracerebral haemorrhage (ICH) due to cerebral amyloid angiopathy (CAA) differs between patients of Eastern and Western origin. Methods: This is a retrospective international cross-sectional study of consecutive first-ever spontaneous ICH patients (including patients with surgical intervention) admitted to one stroke centre in the United Kingdom (Western centre origin) and one in Japan (Eastern centre origin) during the same period. We classified spontaneous ICH into “CAA-related ICH” defined by the Edinburgh CT diagnostic criteria, and “other ICH”. We used multivariable logistic regression analyses to assess the relationship between CAA-ICH and geographical location (Western or Eastern centre origin) or ethnicity (Western [reference], East Asian, or other) with adjustment for confounders. Results: Of 334 patients (median age, 71 years; male, 54%; Western centre origin, 58%), 15% were classified as CAA-ICH, and 85% were defined as other ICH. In multivariable logistic regression analysis, Eastern centre and ethnicity had a lower proportion of CAA-ICH (odds ratio [OR] vs Western centre origin 0.47, 95%CI 0.23-0.98; OR [vs. white] 0.41, 95%CI 0.20-0.97, respectively).The estimated incidence of CAA-related ICH in East Asian was similar to that in White populations, but the rate of other ICH was 2.5-fold higher in East Asian populations. Sensitivity analyses using the modified Boston criteria for diagnosis of CAA-related ICH showed similar results. Conclusions: The proportion CAA-ICH is lower in an Eastern compared to a Western population; this appears to be explained by a higher incidence of ICH due to hypertensive (deep perforator) arteriopathy in East Asian populations.

scholarly journals Cortical superficial siderosis progression in cerebral amyloid angiopathy

Neurology ◽  
2020 ◽  
Vol 94 (17) ◽  
pp. e1853-e1865 ◽  
Author(s):  
Thanakit Pongpitakmetha ◽  
Panagiotis Fotiadis ◽  
Marco Pasi ◽  
Gregoire Boulouis ◽  
Li Xiong ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cerebral Amyloid Angiopathy ◽  
Ordinal Scale ◽  
Superficial Siderosis ◽  
Amyloid Angiopathy ◽  
Cox Regression Analysis ◽  
Multivariable Logistic Regression ◽  
Potential Biomarker ◽  
Cerebral Amyloid ◽  
Cortical Superficial Siderosis

ObjectiveTo investigate the prevalence, predictors, and clinical relevance of cortical superficial siderosis (cSS) progression in cerebral amyloid angiopathy (CAA).MethodsConsecutive patients with symptomatic CAA meeting Boston criteria in a prospective cohort underwent baseline and follow-up MRI within 1 year. cSS progression was evaluated on an ordinal scale and categorized into mild (score 1–2 = cSS extension within an already present cSS focus or appearance of 1 new cSS focus) and severe progression (score 3–4 = appearance of ≥2 new cSS foci). Binominal and ordinal multivariable logistic regression were used to determine cSS progression predictors. We investigated future lobar intracerebral hemorrhage (ICH) risk in survival analysis models.ResultsWe included 79 patients with CAA (mean age, 69.2 years), 56 (71%) with lobar ICH at baseline. cSS progression was detected in 23 (29%) patients: 15 (19%) patients had mild and 8 (10%) severe progression. In binominal multivariable logistic regression, ICH presence (odds ratio [OR], 7.54; 95% confidence interval [CI], 1.75–53.52; p = 0.016) and baseline cSS (OR, 10.41; 95% CI, 2.84–52.83; p = 0.001) were independent predictors of cSS progression. In similar models, presence of disseminated (but not focal) cSS at baseline (OR, 5.58; 95% CI, 1.81–19.41; p = 0.004) was an independent predictor of cSS progression. Results were similar in ordinal multivariable logistic regression models. In multivariable Cox regression analysis, severe cSS progression was independently associated with increased future ICH risk (HR, 5.90; 95% CI, 1.30–26.68; p = 0.021).ConclusionscSS evolution on MRI is common in patients with symptomatic CAA and might be a potential biomarker for assessing disease severity and future ICH risk. External validation of these findings is warranted.

scholarly journals Distribution of lacunes in cerebral amyloid angiopathy and hypertensive small vessel disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2162-2168 ◽  
Author(s):  
Marco Pasi ◽  
Gregoire Boulouis ◽  
Panagiotis Fotiadis ◽  
Eitan Auriel ◽  
Andreas Charidimou ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Close Relationship ◽  
Cerebral Amyloid ◽  
Highly Correlated ◽  
The Relationship

Objective:To evaluate whether the burden of deep and lobar lacunes differs between patients with intracerebral hemorrhage (ICH) with definite/probable cerebral amyloid angiopathy (CAA) per the Boston criteria and hypertensive small vessel disease (HTN-SVD; ICH in basal ganglia, thalami, brainstem).Methods:We defined lobar and deep lacunes similar to the topographic distribution used for ICH and cerebral microbleeds (CMBs). We then compared their distribution between patients with CAA-ICH and those with strictly deep CMB and ICH (HTN-ICH). The independent associations of lacune location with the diagnosis of CAA-ICH and HTN-ICH were evaluated with multivariable models. The relationship between lobar lacunes and white matter hyperintensity (WMH) volume was evaluated by means of partial correlation analyses adjusted for age and a validated visual scale.Results:In our final cohort of 316 patients with ICH, lacunes were frequent (24.7%), with similar rates in 191 patients with CAA and 125 with HTN-ICH (23% vs 27.2%, p = 0.4). Lobar lacunes were more commonly present in CAA (20.4% vs 5.7%, p < 0.001), while deep lacunes were more frequent in HTN-ICH (15.2% vs 2.1%, p < 0.001). After correction for demographics and clinical and neuroimaging markers of SVD, lobar lacunes were associated with CAA (p = 0.003) and deep lacunes with HTN-ICH (p < 0.001). Lobar lacunes in 80% of the cases were at least in contact with WMH, and after adjustment for age, they were highly correlated to WMH volume (r = 0.42, p < 0.001).Conclusions:Lobar lacunes are associated with CAA, whereas deep lacunes are more frequent in HTN-SVD. Lobar lacunes seem to have a close relationship with WMH, suggesting a possible common origin.

Abstract 3208: Sensitivity and Reliability of SWI Compared to T2* GRE MRI for Detection of Microbleeds in Cerebral Amyloid Angiopathy

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ah-Ling Cheng ◽  
Cheryl R McCreary ◽  
M. L Lauzon ◽  
Richard Frayne ◽  
Mayank Goyal ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Intraclass Correlation ◽  
Case Series ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Healthy Controls ◽  
Vessel Disease ◽  
Cerebral Amyloid

Introduction: Case examples and small case series suggest that MRI susceptibility weighted imaging (SWI) may be more sensitive for cerebral microbleed (CMB) detection compared to MRI T2* gradient-recalled echo (GRE). However, there are few data on CMB counts measured by SWI vs. GRE, or inter-rater reliability, in groups of patients with cerebral small vessel disease. We used data from a prospective cohort study of cerebral amyloid angiopathy (CAA), a cerebral small-vessel disease marked by high numbers of CMBs, to quantify the sensitivity and reliability of SWI vs. GRE for CMB detection. Methods: Nine patients with symptomatic CAA (mean age 71±8.3; 7 males and 2 females) and 21 healthy non-CAA controls (mean age 68±6.3; 10 M/11 F) underwent T2* GRE and SWI on a 3.0T MR scanner. Probable CAA was diagnosed according to the Boston criteria prior to study entry using information from clinical MRI with GRE sequences. Two raters (labeled 1 and 2) independently interpreted the GRE and SWI scans blinded to clinical information. The phase-filtered magnitude image was used for SWI interpretation. Agreement reliability was assessed using the kappa coefficient (where a kappa of ≥0.60 indicates good agreement) or the intraclass correlation coefficient (ICC). Results: Overall, the raters identified 1,432 CMBs in the 9 CAA cases (range 1-434 per patient) and 8 CMBs in the healthy controls (range 0-3). Rater 1 identified CMBs in 5/21 healthy controls on SWI and 5/21 on GRE, while rater 2 identified CMBs in 4/21 on SWI and 3/21 on GRE (kappa 0.70 for GRE and 0.57 for SWI). In CAA cases more CMBs were seen on SWI compared to the GRE sequence but the difference was significant only for rater 1 (rater 1: on average 85% more per patient on SWI than on GRE, p=0.008; rater 2: 19% more, p=0.25). Among CAA cases the reliability between raters was poor for GRE (ICC 0.36) but excellent for SWI (0.94, p<0.05 for comparison with GRE). Review suggested that the differing reliability was because rater 1 was less likely than rater 2 to identify faint lesions on GRE as CMB, whereas these lesions were more conspicuous on SWI. If SWI rather than GRE were used to determine CAA status according to the Boston criteria, all 9 CAA cases would remain classified as probable CAA but 2/21 controls would be reclassified as either possible (n=1) or probable (n=1) asymptomatic CAA based on the detection of one or more lobar microbleeds on SWI. Conclusions: SWI confers greater reliability as well as greater sensitivity for CMB detection compared to GRE, and should be the preferred sequence for quantifying CMBs. SWI may more frequently identify lobar microbleeds that could represent asymptomatic CAA. Further research is needed to determine whether the Boston criteria require revision to take into account the greater sensitivity of SWI for CMB detection.

Lacunes, Microinfarcts, and Vascular Dysfunction in Cerebral Amyloid Angiopathy

Neurology ◽  
2021 ◽  
Vol 96 (12) ◽  
pp. e1646-e1654
Author(s):  
Elif Gokcal ◽  
Mitchell J. Horn ◽  
Susanne J. van Veluw ◽  
Aina Frau-Pascual ◽  
Alvin S. Das ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Regression Models ◽  
Cox Regression ◽  
Vascular Dysfunction ◽  
Blood Oxygen Level Dependent ◽  
White Matter Hyperintensity ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Relationship Of ◽  
The Relationship

ObjectiveTo analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).MethodsThe count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level–dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH.ResultsThe cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models (p = 0.048 and p = 0.026, respectively).ConclusionsOur findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.

Abstract W P257: Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Farid Radmanesh ◽  
Guido J Falcone ◽  
Christopher D Anderson ◽  
Thomas W Battey ◽  
Alison M Ayres ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Intracerebral Hemorrhage ◽  
Ct Angiography ◽  
Cerebral Amyloid Angiopathy ◽  
Symptom Onset ◽  
Hematoma Expansion ◽  
Amyloid Angiopathy ◽  
Spot Sign ◽  
Increased Risk ◽  
Cerebral Amyloid

Objectives: Intracerebral hemorrhage (ICH) patients with CT angiography (CTA) spot sign are at increased risk of hematoma expansion and poor outcome. Since ICH is often the acute manifestation of a chronic cerebral vasculopathy, we investigated whether different clinical or imaging characteristics predict spot sign presence in patients with different underlying vasculopathies. Using ICH location as a surrogate for hypertension-related ICH and cerebral amyloid angiopathy-related ICH, we identified risk factors associated with spot sign. METHODS: We retrospectively analyzed a prospective cohort of consecutive spontaneous ICH patients with available CTA. Spot sign presence was ascertained by two independent readers blinded to clinical data. We assessed potential predictors of spot sign be performing uni- and multivariable logistic regression, analyzing deep and lobar ICH separately. RESULTS: 649 patients were eligible, 291 (45%) deep and 358 (55%) lobar ICH. Median time from symptom onset to CTA was 4.5 (IQR 5.2) and 5.7 (IQR 7.4) hours in patients with deep and lobar ICH, respectively. At least one spot sign was present in 76 (26%) deep and 103 (29%) lobar ICH patients. In mutivariable logistic regression, independent predictors of spot sign in deep ICH were warfarin (OR 2.82 [95%CI 1.06-7.57]; p=0.03), time from symptom onset to CTA (OR 0.9 [95%CI 0.81-0.97]; p=0.02), and baseline ICH volume (OR 1.27 [95%CI 1.14-1.43]; p=2.5E-5; per 10 mL increase). Predictors of spot sign in lobar ICH were preexisting dementia (OR 2.7 [95%CI 1.15-6.43]; p=0.02), warfarin (OR 4.01 [95%CI 1.78-9.29]; p=0.009), and baseline ICH volume (OR 1.27 [95%CI 1.17-1.39]; p=5.4E-8; per 10 mL increase). As expected, spot sign presence was a strong predictor of hematoma expansion in both deep (OR 3.52 [95%CI 1.72-7.2]; p=0.0005) and lobar ICH (OR 6.53 [95%CI 3.23-13.44]; p=2.2E-7). CONCLUSIONS: The most potent associations with spot sign are shared by deep and lobar ICH, suggesting that ICH caused by different vasculopathic processes share biological features. The relationship between preexisting dementia and spot sign in lobar ICH, but not deep ICH, suggests that ICH occurring in the context of more advanced cerebral amyloid angiopathy may be more likely to have prolonged bleeding.

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

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3600-3607 ◽  
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.

Abstract TP339: Simultaneous Multiple Intracerebral Hemorrhages (SMICH)

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Teddy Wu ◽  
Nawaf Yassi ◽  
Darshan Shah ◽  
Minmin Ma ◽  
Gagan Sharma ◽  
...  
Keyword(s):  
Regression Models ◽  
Clinical Characteristics ◽  
Amyloid Angiopathy ◽  
Royal Melbourne Hospital ◽  
Aneurysmal Rupture ◽  
Logistic Regression Models ◽  
Lower Baseline ◽  
Intracerebral Hemorrhages ◽  
Cerebral Amyloid ◽  
Underlying Pathology

Background and Purpose: Simultaneous multiple intracerebral hemorrhages (SMICH) are uncommon. Few single center studies have analyzed characteristics and outcome of SMICH. We analyzed clinical characteristics and outcome of SMICH patients from two comprehensive stroke centers. Methods: Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study were screened for SMICH. ICH etiology was classified according to the SMASH-U classification system. ICH due to trauma, tumor and aneurysmal rupture were excluded. Baseline clinical and radiological characteristics and 90-day mortality were compared between SMICH and single ICH patients. Association of SMICH with 90-day mortality was assessed in multivariable logistic regression models adjusted for predictors of ICH outcome. Results: 1452 patients were included in the analysis and 85 (5.9%) were classified as SMICH. SMICH were more often female (58% vs 42%;p=0.004), had lower baseline Glasgow Coma Scale (12 vs 14;p=0.008), and more frequent lobar location (59% v 34%;p<0.001) compared to single ICH. The SMASH-U etiology of SMICH patients was less often hypertensive (20% vs 37%;p=0.001), more other systemic coagulopathy (12% vs 3%;p<0.001) and trended towards more cerebral amyloid angiopathy (32% vs 23%;p=0.071). SMICH was not associated with 90-day mortality on univariate (37% vs 35%;p=0.635), multivariable (OR 0.783 95%CI 0.401-1.529;p=0.473), or propensity score matched analyses (OR 0.817 95% CI 0.400-1.668,p=0.578). Conclusion: SMICH occurs in approximately 1 in 20 ICH with more often lobar located hematomas, less often hypertensive and associated with more systemic coagulopathy. The mortality is similar to single ICH. Given varied etiologies, SMICH management should target the underlying pathology.

scholarly journals Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage

Neurology ◽  
2017 ◽  
Vol 88 (9) ◽  
pp. 878-884 ◽  
Author(s):  
Gregoire Boulouis ◽  
Andreas Charidimou ◽  
Michael J. Jessel ◽  
Li Xiong ◽  
Duangnapa Roongpiboonsopit ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Summary Score ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Cognitive Symptoms ◽  
Vessel Disease ◽  
Age Related ◽  
Cerebral Amyloid

Objective:Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without intracerebral hemorrhage (ICH) typically present with transient focal neurologic episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between patients with CAA first presenting with TFNEs vs cognitive symptoms.Methods:A total of 647 patients presenting either to a stroke department (n = 205) or an outpatient memory clinic (n = 442) were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified, including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMHs). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models.Results:There were 261 patients with probable CAA included. After adjustment for confounders, patients first seen for TFNEs (n = 97) demonstrated a higher prevalence of cSS (p < 0.0001), higher WMH volumes (p = 0.03), and a trend toward higher CMB counts (p = 0.09). The total SVD summary score was higher in patients seen for TFNEs (adjusted odds ratio per additional score point 1.46, 95% confidence interval 1.16–1.84, p = 0.013).Conclusions:Patients with probable CAA without ICH first evaluated for TFNEs bear a higher burden of structural MRI SVD-related damage compared to those first seen for cognitive symptoms. This study sheds light on neuroimaging profile differences across clinical phenotypes of patients with CAA without ICH.

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