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Magnetic Resonance Imaging White Matter Hyperintensities and Brain Volume in the Prediction of Mild Cognitive Impairment and Dementia
Eric E. Smith, MD, MPH, FRCPC;
Svetlana Egorova, PhD;
Deborah Blacker, MD, ScD;
Ronald J. Killiany, PhD;
Alona Muzikansky, MS;
Bradford C. Dickerson, MD;
Rudolph E. Tanzi, PhD;
Marilyn S. Albert, PhD;
Steven M. Greenberg, MD, PhD;
Charles R. G. Guttmann, MD
Arch Neurol. 2008;65(1):94-100.
Objective To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia.
Design Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean.
Setting General community.
Patients Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI).
Main Outcome Measures Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at baseline). Cox proportional hazards models were used for multivariable analysis.
Results High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P = .01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P = .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P < .001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P = .03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P = .02), but not AD dementia.
Conclusions These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.
Author Affiliations: Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, Boston (Drs Smith and Greenberg); Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Boston (Drs Egorova and Guttmann); Gerontology Research Unit, Department of Psychiatry, Massachusetts General Hospital (Dr Blacker and Ms Muzikansky); Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston (Dr Killiany); Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital, Boston (Drs Dickerson and Tanzi); and Johns Hopkins Medical Center, Baltimore, Maryland (Dr Albert).
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