Cited by 403Dementia and Cognitive Impairment ResearchIntracerebral and Subarachnoid Hemorrhage ResearchCerebrovascular and genetic disorders

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Association of Cerebral Microbleeds With Cognitive Decline and Dementia

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Akoudad, Saloua, Wolters, Frank J., Viswanathan, Anand, de Bruijn, Renée F., van der Lugt, Aad, Hofman, Albert, Koudstaal, Peter J., Ikram, M. Arfan, Vernooij, Meike W.·2016·JAMA Neurology

DOI 10.1001/jamaneurol.2016.1017PMC PMC5966721

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Abstract

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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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 Netherlands
Corresponding author: Ikram, M. Arfan
ORCID: Wolters, Frank J.
Viswanathan, Anand
van der Lugt, Aad
Koudstaal, Peter J.
Ikram, M. Arfan
Vernooij, Meike W.
Venue: JAMA Neurology
Publisher: American Medical Association (AMA)
Published: 2016-08-01
Volume: 73
Issue: 8
Pages: 934
ISSN: 2168-6149 (ISSN-L)
DOI: 10.1001/jamaneurol.2016.1017
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
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 › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
Health Sciences › Medicine › Clinical 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

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Association of Cerebral Microbleeds With Cognitive Decline and Dementia

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