The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: a longitudinal study in a memory clinic

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Abstract

Background

We investigated the relevance of various imaging markers for the clinical trajectory of cerebral amyloid angiopathy (CAA) patients in a memory clinic.

Methods

A total of 226 patients with probable CAA were included in this study with a mean follow-up period of 3.5 ± 2.7 years. Although all had more than one follow-up visit, 173 underwent follow-up Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SB) ranging from 2 to 15 time points. Among 226, 122 patients underwent amyloid-β (Aβ) PET imaging. The prevalence of intracerebral hemorrhage (ICH) and its imaging predictors was investigated. The effects of CAA imaging markers and Aβ PET positivity on longitudinal cognition based on the MMSE and CDR-SB were evaluated using mixed effects models.

Results

During the follow-up, 10 (4.4%) patients developed ICH: cortical superficial siderosis (cSS; hazard ratio [HR], 6.45) and previous lobar ICH (HR, 4.9), but lobar cerebral microbleeds (CMBs) were not predictors of ICH development. The presence of CMIs ( p = 0.045) and Aβ positivity ( p = 0.002) were associated with worse MMSE trajectory in CAA patients. Regarding CDR-SB trajectory, only Aβ positivity was marginally associated with worse longitudinal change ( p = 0.050).

Conclusion

The results of the present study indicated that various imaging markers in CAA patients have different clinical relevance and predictive values for further clinical courses.

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Most cited references 49

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Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.

N. Tzourio-Mazoyer, B Landeau, D Papathanassiou … (2003)

An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.

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Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

Joanna M. Wardlaw, Eric E. Smith, Geert J Biessels … (2014)

Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

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Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy.

J. Linn, A. Halpin, P Demaerel … (2010)

Cerebral amyloid angiopathy (CAA) typically presents with lobar intracerebral macrohemorrhages (ICH) or microbleeds (MBs). Several case reports also found superficial siderosis (SS) in patients with CAA. We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage. We retrospectively analyzed the T2*-weighted MRIs of 38 patients with histopathologically proven CAA and of 22 control patients with histopathologically proven non-CAA ICHs regarding the presence of ICHs, MBs, and SS. We compared the sensitivity and specificity of the classic Boston criteria to that of modified criteria, which included SS as a criterion. ICHs were present in 71% of the patients with CAA, and in all control patients. MBs were found in 47.4% of patients with CAA and in 22.7% of controls. SS was detected in 60.5% of patients with CAA, but in none of the controls. The classic criteria had a sensitivity of 89.5% for CAA-related hemorrhage, while inclusion of SS increased their sensitivity to 94.7% (not significant). On the contrary, the specificity of the Boston criteria was 81.2% both for the classic and for the modified criteria. Superficial siderosis (SS) occurs with high prevalence in cerebral amyloid angiopathy (CAA) and is rare in non-CAA forms of intracerebral hemorrhages. Thus, we propose that inclusion of SS in the Boston criteria might enhance their sensitivity for CAA-related hemorrhage without loss of specificity.

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Author and article information

Contributors

Hyemin Jang: hmjang57@gmail.com

Min Young Chun: myc5198@gmail.com

Hee Jin Kim: evekhj@gmail.com

Duk L. Na: dukna@naver.com

Sang Won Seo: sangwonseo@empal.com , sw72.seo@samsung.com

Journal

Journal ID (nlm-ta): Alzheimers Res Ther

Journal ID (iso-abbrev): Alzheimers Res Ther

Title: Alzheimer's Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-9193

Publication date (Electronic): 12 January 2023

Publication date PMC-release: 12 January 2023

Publication date Collection: 2023

Volume: 15

Electronic Location Identifier: 14

Affiliations

[1 ]GRID grid.414964.a, ISNI 0000 0001 0640 5613, Samsung Alzheimer’s Convergence Research Center, , Samsung Medical Center, ; Seoul, South Korea

[2 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Departments of Neurology, Samsung Medical Center, , Sungkyunkwan University School of Medicine, ; 81 Irwon-ro, Gangnam-gu, Seoul, 06351 South Korea

[3 ]GRID grid.414964.a, ISNI 0000 0001 0640 5613, Neuroscience Center, Samsung Medical Center, ; Seoul, South Korea

[4 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Department of Health Sciences and Technology, SAIHST, , Sungkyunkwan University, ; Seoul, South Korea

[5 ]Happymind Clinic, Seoul, South Korea

Article

Publisher ID: 1161

DOI: 10.1186/s13195-023-01161-5

PMC ID: 9835259

PubMed ID: 36635759

SO-VID: 7e19102e-fbe0-4b50-b998-d2c4ef58fe3a

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 9 February 2022

Date accepted : 2 January 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;

Award ID: 2020R1A2C1009778

Funded by: FundRef http://dx.doi.org/10.13039/501100003625, Ministry of Health and Welfare;

Award ID: HR21C0885

Funded by: Samsung Medical Center

Funded by: FundRef http://dx.doi.org/10.13039/501100003710, Korea Health Industry Development Institute;

Award ID: HU22C0052

Funded by: Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT

Award ID: HU20C0414

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: cerebral amyloid angiopathy,prognosis,cognition,amyloid β,microbleed,cortical superficial siderosis

Data availability:

ScienceOpen disciplines: Neurology

Keywords: cerebral amyloid angiopathy, prognosis, cognition, amyloid β, microbleed, cortical superficial siderosis

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The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: a longitudinal study in a memory clinic

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Abstract

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Karger: Neurology and Neuroscience

Most cited references 49

Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy.

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