Regional White Matter Hyperintensity Volume, Not Hippocampal Atrophy, Predicts Incident Alzheimer Disease in the Community | Cerebrovascular Disease | JAMA Neurology | JAMA Network
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Original Contribution
Dec 2012

Regional White Matter Hyperintensity Volume, Not Hippocampal Atrophy, Predicts Incident Alzheimer Disease in the Community

Author Affiliations

Author Affiliations: Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Brickman, Manly, Stern, and Mayeux and Messrs Provenzano, Muraskin, and Apa), Gertrude H. Sergievsky Center (Drs Brickman, Manly, Blum, Stern, and Mayeux), and Departments of Neurology (Drs Brickman, Manly, Blum, Stern, and Mayeux), Psychiatry (Drs Stern and Mayeux), and Medicine (Dr Luchsinger), College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health (Drs Luchsinger and Mayeux), Columbia University, New York, New York; and Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston (Dr Brown).

Arch Neurol. 2012;69(12):1621-1627. doi:10.1001/archneurol.2012.1527

Background New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear.

Objective To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study.

Design A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York.

Setting The Washington Heights/Inwood Columbia Aging Project.

Participants Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements.

Main Outcome Measure Incident AD.

Results White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049).

Conclusions The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.