Association of Cerebral Microbleeds With Cognitive Decline and Dementia
Open accessAbstract
IMPORTANCE: Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear. OBJECTIVE: To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population. DESIGN, SETTING, AND PARTICIPANTS: The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards. EXPOSURES: Cerebral microbleed presence, location, and number. MAIN OUTCOMES AND MEASURES: Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia. RESULTS: In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64). CONCLUSIONS AND RELEVANCE: In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.
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Studies in unimpaired populations longitudinally followed up showed high microbleed number (>3-4) is associated with an increased risk of cognitive deterioration and dementia.
“Studies in unimpaired populations that were longitudinally followed up showed that high microbleed number (>3–4) is associated with an increased risk of cognitive deterioration and dementia [41, 42].”
From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [41]
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- Authors
- Akoudad, S., Wolters, F. J., Viswanathan, A., de Bruijn, R. F., van der Lugt, A., Hofman, A., Koudstaal, P. J., Ikram, M. A., & Vernooij, M. W.
- Affiliations
- Erasmus MC (NL)
- Harvard University (US)
- Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands3Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Corresponding author
- Ikram, M. Arfan
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-08-01
- Volume
- 73
- Issue
- 8
- Pages
- 934
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5966721
- OpenAlex
- W2410623364
- Cited by
- 403
- References
- 58
- Citations by year
- 2026: 34 · 2025: 34 · 2024: 40 · 2023: 48 · 2022: 52 · 2021: 53 · 2020: 44 · 2019: 35 · 2018: 26 · 2017: 25 · 2016: 9 · 2015: 1
- FWCI
- 28.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- European Commission
- ZonMw (90700435)
- Erasmus Medisch Centrum
- National Institutes of Health
- Erasmus Universitair Medisch Centrum Rotterdam
- National Institute on Aging (R01AG047975)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral microbleeds, cognitive decline, dementia, lobar microbleeds, executive function, processing speed, memory impairment, white matter hyperintensities, cerebral small vessel disease, vascular dementia, Alzheimer's disease, amyloid, Rotterdam Study, general population, incident dementia risk
- MeSH terms
- Aged, Aged, 80 and over, Brain, Cerebral Hemorrhage, Cognition Disorders, Dementia, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Netherlands, Neuropsychological Tests, Psychiatric Status Rating Scales, Retrospective Studies, Statistics as Topic, Community Health Planning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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