Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative

Owen Carmichael, Christopher Schwarz, David Drucker, Evan Fletcher, Danielle Harvey, Laurel Beckett, Clifford R. Jack, Michael Weiner, Charles DeCarli

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Objective: To evaluate relationships between magnetic resonance imaging (MRI)-based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. Design: Convenience sample in a clinical trial design. Subjects: A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMHvolume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADASCog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. Results: Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. Conclusions: White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials.

Original languageEnglish (US)
Pages (from-to)1370-1378
Number of pages9
JournalArchives of neurology
Volume67
Issue number11
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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