Cortical atrophy in patients with cerebral amyloid angiopathy: a case-control study

AbstractObjectiveTo study blood anti-Aβ antibodies in the context of spontaneous inflammatory or hemorrhagic CAA manifestations, which are similar to complications occurring after monoclonal anti-Aβ antibody immunotherapies.MethodsIn this case-control study, serum anti-Aβ antibody isotype, concentration, avidity, and reactivity toward soluble or fibrillary Aβ1-40 and Aβ1-42 isoforms were assessed using an ELISA-based multiplex analysis. Anti-Aβ serologic patterns were defined in CAA and CAA subgroups using multivariable logistic regression analyses.ResultsFourty-one healthy aged controls and 64 CAA patients were recruited: 46 with hemorrhagic features (CAA-he) and 18 with CAA-related inflammation (CAA-ri). As compared to controls, the most striking features of CAA-related serological profiles were the following: i) both CAA-he and CAA-ri patients displayed lower binding diversity of anti-soluble Aβ1-40 IgM; ii) CAA-he patients displayed higher anti-soluble Aβ1-40 / fibrillary Aβ1-42 IgG4 concentrations ratio and higher anti-soluble Aβ1-42 IgG4 and IgA avidity; iii) CAA-ri patients displayed higher binding diversity of anti-soluble Aβ1-40 IgG3 and higher anti-fibrillary/soluble Aβ1-42 IgG4 dilution curve steepness ratio.ConclusionThis proof-of-concept study revealed anti-Aβ antibody variations in CAA patients, some of which were associated to CAA clinical phenotypes, unveiling pathophysiological insights regarding CAA-hemorrhagic and inflammatory related events.

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Cortical Thickness and Its Association with Clinical Cognitive and Neuroimaging Markers in Cerebral Amyloid Angiopathy

Journal of Alzheimer s Disease ◽

10.3233/jad-210138 ◽

2021 ◽

pp. 1-9

Author(s):

Arsenije Subotic ◽

Cheryl R. McCreary ◽

Feryal Saad ◽

Amanda Nguyen ◽

Ana Alvarez-Veronesi ◽

...

Keyword(s):

Cognitive Decline ◽

Cerebral Amyloid Angiopathy ◽

Cortical Thickness ◽

Vascular Reactivity ◽

Cortical Atrophy ◽

White Matter Hyperintensity ◽

Amyloid Angiopathy ◽

Healthy Controls ◽

Normative Study ◽

Cerebral Amyloid

Background: Cerebral amyloid angiopathy (CAA) contributes to brain neurodegeneration and cognitive decline, but the relationship between these two processes is incompletely understood. Objective: The purpose of this study is to examine cortical thickness and its association with cognition and neurodegenerative biomarkers in CAA. Methods: Data were collected from the Functional Assessment of Vascular Reactivity study and the Calgary Normative Study. In total, 48 participants with probable CAA, 72 cognitively normal healthy controls, and 24 participants with mild dementia due to AD were included. Participants underwent an MRI scan, after which global and regional cortical thickness measurements were obtained using FreeSurfer. General linear models, adjusted for age and sex, were used to compare cortical thickness globally and in an AD signature region. Results: Global cortical thickness was lower in CAA compared to healthy controls (mean difference (MD) –0.047 mm, 95% confidence interval (CI) –0.088, –0.005, p = 0.03), and lower in AD compared to CAA (MD –0.104 mm, 95% CI –0.165, –0.043, p = 0.001). In the AD signature region, cortical thickness was lower in CAA compared to healthy controls (MD –0.07 mm, 95% CI –0.13 to –0.01, p = 0.02). Within the CAA group, lower cortical thickness was associated with lower memory scores (R2 = 0.10; p = 0.05) and higher white matter hyperintensity volume (R2 = 0.09, p = 0.04). Conclusion: CAA contributes to neurodegeneration in the form of lower cortical thickness, and this could contribute to cognitive decline. Regional overlap with an AD cortical atrophy signature region suggests that co-existing AD pathology may contribute to lower cortical thickness observed in CAA.

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Clinical features distinguish cerebral amyloid angiopathy-associated convexity subarachnoid haemorrhage from suspected TIA

Journal of Neurology ◽

10.1007/s00415-019-09558-9 ◽

2019 ◽

Vol 267 (1) ◽

pp. 133-137 ◽

Cited By ~ 2

Author(s):

Joel Elliot Dane Stanton ◽

Arvind Chandratheva ◽

Duncan Wilson ◽

Isabel Charlotte Hostettler ◽

Saiful Islam ◽

...

Keyword(s):

Subarachnoid Haemorrhage ◽

Clinical Features ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Angiopathy ◽

Retrospective Case ◽

Presenting Symptoms ◽

Clinical Databases ◽

Cerebral Amyloid ◽

And Gender ◽

Control Study

Abstract Objective To identity clinical features that distinguish between cerebral amyloid angiopathy (CAA)-associated convexity subarachnoid haemorrhage (cSAH) and suspected TIA. Methods We undertook a single-centre, retrospective case–control study. We identified cases [patients with cSAH presenting with transient focal neurological episodes (TFNE)] from radiological and clinical databases of patients assessed at the National Hospital for Neurology and Neurosurgery and UCLH Comprehensive Stroke Service. We identified age- and gender-matched controls at a 1:4 ratio from a database of consecutive suspected TIA clinic attendances at UCLH. We compared presenting symptoms and vascular risk factors between cases and controls. Results We included 19 patients with cSAH-associated TFNE and 76 matched controls with suspected TIA. Migratory (spreading) symptoms (32% vs. 3%, OR 17.3; p = 0.001), sensory disturbance (47% vs. 14%, OR 5.3; p = 0.003,) and recurrent stereotyped events (47% vs. 19%, OR 3.7; p = 0.02,) occurred more frequently in patients with cSAH compared to controls. Hypercholesterolaemia was less common in patients with cSAH (16% vs 53%, OR 0.17; p = 0.008). Conclusion Simple clinical features could help distinguish cSAH-associated TFNE from suspected TIA, with relevance for investigation and management, including the use of antithrombotic drugs.

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Bilateral Anterior Cortical Atrophy and Subcortical Atrophy in Reduplicative Paramnesia: A Case-Control Study of Computed Tomography in 10 Patients

The Canadian Journal of Psychiatry ◽

10.1177/070674379904400706 ◽

1999 ◽

Vol 44 (7) ◽

pp. 685-689 ◽

Cited By ~ 20

Author(s):

Anthony B Joseph ◽

Daniel H O'Leary ◽

Robert Kurland ◽

Hadyn D Ellis

Keyword(s):

Computed Tomography ◽

Case Control Study ◽

Case Control ◽

Cortical Atrophy ◽

Reduplicative Paramnesia ◽

Control Study

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The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community A population-based and nested case-control study in rural Ecuador (The Atahualpa Project)

Dementia & Neuropsychologia ◽

10.1590/s1980-57642014dn84000008 ◽

2014 ◽

Vol 8 (4) ◽

pp. 351-355

Author(s):

Oscar H. Del Brutto ◽

Robertino M. Mera ◽

Mauricio Zambrano ◽

Julio Lama

Keyword(s):

Brain Damage ◽

Case Control Study ◽

Case Control ◽

Cognitive Test ◽

Cortical Atrophy ◽

Reliable Estimate ◽

Structural Brain Damage ◽

Nested Case Control ◽

Control Study ◽

Structural Brain

OBJECTIVE: We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. METHODS: Atahualpa residents aged ≥ 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (≤ 22 points) and in matched controls without dementia. RESULTS: Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored ≤ 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (β=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). CONCLUSION: The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage.

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Cerebral Beta Amyloid Angiopathy Is a Risk Factor for Cerebral Ischemic Infarction. A Case Control Study in Human Brain Biopsies

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/59.9.768 ◽

2000 ◽

Vol 59 (9) ◽

pp. 768-773 ◽

Cited By ~ 80

Author(s):

Diego Cadavid ◽

Hernando Mena ◽

Kelly Koeller ◽

Robert A. Frommelt

Keyword(s):

Risk Factor ◽

Human Brain ◽

Case Control Study ◽

Beta Amyloid ◽

Case Control ◽

Amyloid Angiopathy ◽

Ischemic Infarction ◽

Cerebral Ischemic ◽

Control Study

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Atrophy patterns in cerebral amyloid angiopathy with and without cortical superficial siderosis

Neurology ◽

10.1212/wnl.0000000000005524 ◽

2018 ◽

Vol 90 (20) ◽

pp. e1751-e1758

Author(s):

Joonho Kim ◽

Han Kyu Na ◽

Jeong-Hyeon Shin ◽

Hee Jin Kim ◽

Sang Won Seo ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Hippocampal Volume ◽

Cortical Atrophy ◽

Superficial Siderosis ◽

Cognitively Impaired ◽

Amyloid Angiopathy ◽

Amyloid Pet ◽

Cognitively Normal ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

ObjectiveTo investigate differential atrophy patterns based on the presence of cortical superficial siderosis (cSS) and the role of cSS in predicting amyloid positivity in memory clinic patients fulfilling the diagnostic criteria for probable cerebral amyloid angiopathy (CAA).MethodsWe retrospectively collected data from 44 cognitively impaired patients with probable CAA who underwent 3-dimensional, T1-weighted MRIs (cSS+, n = 27; cSS−, n = 17). Amyloid-positive patients with Alzheimer disease (AD) (n = 56) and amyloid-negative cognitively normal participants (n = 34) were recruited as controls. Among the patients with CAA who underwent amyloid-PET scans (75.0%), we investigated whether amyloid-negative cases were unevenly distributed based on cSS presentation. APOE genotypes, Mini-Mental State Examination scores, and cortical atrophy pattern along with hippocampal volume were compared across groups.ResultsTen patients with probable CAA presented amyloid negativity and all of them belonged to the cSS− group (58.8%). Compared to the cSS− group, the cSS+ group presented higher APOE ε4 frequency, worse memory dysfunction, and lower hippocampal volume. Compared with cognitively normal participants, the cSS+ group exhibited atrophy in the precuneus, posterior cingulate, parietotemporal, superior frontal, and medial temporal areas, a pattern similar to AD-specific atrophy. The cSS− group exhibited atrophy in the parietotemporal, superior frontal, and precentral regions.ConclusionOur findings imply that the current version of the Boston criteria may not be sufficient enough to remove non-CAA cases from a cognitively impaired population, especially in the absence of cSS. Patients with probable CAA presenting cSS appear to reflect a CAA phenotype that shares pathologic hallmarks with AD, providing insight into the CAA-to-AD continuum.

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