Journal
NEUROLOGY
Volume 76, Issue 17, Pages 1492-1499Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318217e7c8
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Funding
- National Institute on Aging [P01 AG04953, R01 AG26484]
- National Institute of Neurological Disorders and Stroke [R01 NS062028]
- NIH
- Alberta Heritage Foundation for Medical Research
- Canadian Institutes for Health Research
- Heart and Stroke Foundation of Canada
- Canadian Stroke Network
- Hotchkiss Brain Institute
- NIH/NINR
- NIH (NCRR/NIBIB/NIA/NINDS)
- Ellison Medical Foundation
- Birmingham Foundation
- MINDlink Foundation
- Sidney R. Baer, Jr. Foundation
- NIH/NIA
- Alzheimer's Association
- Pfizer Inc
- GE Healthcare
- NIH (NIA/NHLBI)
- NIH (NINDS/NIA)
- Cure Alzheimer's Foundation
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Objectives: MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume. Methods: Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software. Results: Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally. Conclusions: Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes. Neurology (R) 2011;76:1492-1499
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