Cerebral microbleeds are associated with worse cognitive function
The Rotterdam Scan Study
Abstract
Objective:
Cerebral microbleeds are frequently found in the general elderly population and may reflect underlying vascular disease, but their role in cognitive function is unknown.
Methods:
We investigated the association between cerebral microbleeds and performance in multiple cognitive domains in 3,979 persons without dementia (mean age, 60.3 years). Mini-Mental State Examination (MMSE) score and neuropsychological tests were used to assess global cognition and the following cognitive domains: memory, information processing speed, executive function, and motor speed. We used number of microbleeds as continuous variable, and additionally distinguished between persons with no microbleeds, 1 microbleed, 2–4 microbleeds, and ≥5 microbleeds. The association of microbleeds with different cognitive domains was estimated using linear regression models. Additional adjustments were made for vascular risk factors, brain atrophy, and other imaging markers of cerebral small vessel disease. We stratified analyses by location of microbleeds.
Results:
A higher number of microbleeds was associated with lower MMSE score and worse performance on tests of information processing speed and motor speed. When analyzed per category, presence of 5 or more microbleeds was associated with worse performance in all cognitive domains, except memory. These associations were most robust in participants with strictly lobar microbleeds, whereas after additional adjustments associations disappeared for deep or infratentorial microbleeds.
Conclusions:
Presence of numerous microbleeds, especially in a strictly lobar location, is associated with worse performance on tests measuring cognitive function, even after adjustments for vascular risk factors and other imaging markers of small vessel disease. These results suggest an independent role for microbleed-associated vasculopathy in cognitive impairment.
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Study Funding
The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMW), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Dr. Meike W. Vernooij was supported by a grant from the Alzheimer's Association (NIRG-09-13168). This study was also supported by the Netherlands Organization for Scientific Research (NWO) grants 948-00-010 and 918-46-615 and an Erasmus MC grant for translational research. The funding sources had no role in the design or conduct of the study, data collection, data analysis, data interpretation, or in writing or approval of this report.
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Information & Authors
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Published In
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Copyright © 2012 by AAN Enterprises, Inc.
Publication History
Received: June 23, 2011
Accepted: September 23, 2011
Published online: January 18, 2012
Published in print: January 31, 2012
Disclosure
Dr. Poels reports no disclosures. Dr. Ikram has received research support from the Nederlandse Hartstichting and the Internationaal Parkinson Fonds and serves on the editorial board for Neuroepidemiology. Dr. Van der Lugt receives research support from Bayer Schering Pharma, the Dutch Heart Foundation, and the Alzheimer's Association USA and has served as a consultant for GE Healthcare. Dr. Hofman has received funding for travel from GlaxoSmithKline; serves as Editor-in-Chief for the European Journal of Epidemiology; receives publishing royalties for Grondslagen der epidemiologie (Elsevier, 2008), Klinische epidemiologie (Elsevier, 2000), and Investigating Neurological Disease (Cambridge University Press, 1996); and receives research support from the Netherlands Genomics Initiative for the Rotterdam Study and from the Ministry of Health for the Generation R study. Dr. Niessen serves as an Associate Editor for IEEE Transactions on Medical Imaging and Associate Editor for Medical Image Analysis. Dr. Krestin serves on the editorial boards of MagMa, Abdominal Imaging, European Radiology, Investigative Radiology, Radiologica Medica, Contrast Media, and Molecular Imaging; serves as a consultant for GE Healthcare; has received honoraria from Bayer Schering Pharma, GE Healthcare, and Siemens Medical Solutions; and receives/has received research support from Bayer Schering Pharma, GE Healthcare, Philips Healthcare, Siemens Medical Solutions, the European Commission FP6 and FP7, the Dutch Science Organization, Cancer Foundation Netherlands, and Heart Foundation Netherlands. Dr. Breteler serves on editorial advisory boards for Neuroepidemiology, Alzheimer's & Dementia, and Stroke; and receives research support from Pfizer Inc, the Netherlands Organization for Scientific Research, the Alzheimer's Association USA, the NIH, the Internationale Stichting Alzheimer Onderzoek (ISAO), the Dutch Cancer Society, the Dutch Parkinsonfonds, and the Netherlands Brain Foundation. Dr. Vernooij receives research support from the Alzheimer's Association.
Authors
Author Contributions
Dr. Poels: drafting the manuscript for content, analysis or interpretation of data, acquisition of data, statistical analysis. Dr. Ikram: revising the manuscript for content, acquisition of data. Dr. van der Lugt: revising the manuscript for content. Dr. Hofman: revising the manuscript for content, study concept or design, obtaining funding. Dr. Niessen: revising the manuscript for content. Dr. Krestin: revising the manuscript for content, obtaining funding. Dr. Breteler: revising the manuscript for content, study concept or design, obtaining funding. Dr. Vernooij: revising the manuscript for content, analysis or interpretation of data, acquisition of data, study supervision or coordination. Dr. Poels and Dr. Vernooij had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the statistical data analysis.
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