Prevalence and risk factors of cerebral microhemorrhages and superficial siderosis in cognitively unimpaired older adults: analysis from the CHARIOT-PRO SubStudy
Author(s)
Type
Journal Article
Abstract
INTRODUCTION
Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.
METHODS
This cross-sectional study included 1414 cognitively unimpaired, treatment-naïve individuals aged 60 to 85 years from the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. Relationships between CMHs/SS and cardiovascular risk factors, amyloid beta (Aβ) load, apolipoprotein E (APOE) ε4 status, educational attainment, and white matter hyperintensities were investigated using regression analyses and structural equation modeling.
RESULTS
CMHs were observed in 8.3% of participants and SS in 1.3%. Significant risk factors for CMHs included age and hypertension. Higher education attainment appeared to have a protective effect. Elevated amyloid is a risk factor, particularly when adjusting for APOE ε4 status in individuals aged 70 or younger.
DISCUSSION
Increasing age and hypertension are significant risk factors of CMHs. Higher educational attainment may offer a protective effect.
Highlights
Of the 1414 participants from the CHARIOT-PRO SubStudy (CPSS), CMHs were present in 118 (8.3%), and SS was present in 18 (1.3%).
Age and hypertension were identified as significant risk factors for CMHs, and the latter had a stronger association with the presence of CMHs among female participants. Having a bachelor's degree or higher was found to be protective.
Elevated brain amyloid burden, particularly when adjusted for APOE ε4 carrier status, was identified as a risk factor in individuals aged 70 years and below.
Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.
METHODS
This cross-sectional study included 1414 cognitively unimpaired, treatment-naïve individuals aged 60 to 85 years from the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. Relationships between CMHs/SS and cardiovascular risk factors, amyloid beta (Aβ) load, apolipoprotein E (APOE) ε4 status, educational attainment, and white matter hyperintensities were investigated using regression analyses and structural equation modeling.
RESULTS
CMHs were observed in 8.3% of participants and SS in 1.3%. Significant risk factors for CMHs included age and hypertension. Higher education attainment appeared to have a protective effect. Elevated amyloid is a risk factor, particularly when adjusting for APOE ε4 status in individuals aged 70 or younger.
DISCUSSION
Increasing age and hypertension are significant risk factors of CMHs. Higher educational attainment may offer a protective effect.
Highlights
Of the 1414 participants from the CHARIOT-PRO SubStudy (CPSS), CMHs were present in 118 (8.3%), and SS was present in 18 (1.3%).
Age and hypertension were identified as significant risk factors for CMHs, and the latter had a stronger association with the presence of CMHs among female participants. Having a bachelor's degree or higher was found to be protective.
Elevated brain amyloid burden, particularly when adjusted for APOE ε4 carrier status, was identified as a risk factor in individuals aged 70 years and below.
Date Issued
2025-08-01
Date Acceptance
2025-07-07
Citation
Alzheimer's and Dementia, 2025, 21 (8)
ISSN
1552-5260
Publisher
Wiley
Start Page
e70594
Journal / Book Title
Alzheimer's and Dementia
Volume
21
Issue
8
Copyright Statement
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40832697
Subjects
APOE ε4
ARIA
Alzheimer's disease
CAA
MRI
PET
amyloid
amyloid‐related imaging abnormalities
anti‐amyloid therapies
cerebral microhemorrhages
cognitively unimpaired
dementia
hypercholesterolemia
hypertension
superficial siderosis
white matter hyperintensities
Humans
Aged
Female
Male
Risk Factors
Cross-Sectional Studies
Aged, 80 and over
Cerebral Hemorrhage
Prevalence
Middle Aged
Apolipoprotein E4
Siderosis
Magnetic Resonance Imaging
Amyloid beta-Peptides
Prospective Studies
Publication Status
Published
Coverage Spatial
United States
Article Number
e70594
Date Publish Online
2025-08-20