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 J Harvey, Laurel A Beckett, Clifford R. Jack, Michael Weiner, Charles DeCarli

Research output: Contribution to journalArticle

134 Citations (Scopus)

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

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Leukoencephalopathies
Neuroimaging
Cognition
Alzheimer Disease
Magnetic Resonance Imaging
Clinical Trials
Sex Education
Apolipoproteins E
White Matter
Alzheimer's Disease
Dementia
Protons
Genotype
Outcome Assessment (Health Care)
Mental State
Brain

ASJC Scopus subject areas

  • Clinical Neurology

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Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative. / Carmichael, Owen; Schwarz, Christopher; Drucker, David; Fletcher, Evan; Harvey, Danielle J; Beckett, Laurel A; Jack, Clifford R.; Weiner, Michael; DeCarli, Charles.

In: Archives of Neurology, Vol. 67, No. 11, 11.2010, p. 1370-1378.

Research output: Contribution to journalArticle

Carmichael, Owen ; Schwarz, Christopher ; Drucker, David ; Fletcher, Evan ; Harvey, Danielle J ; Beckett, Laurel A ; Jack, Clifford R. ; Weiner, Michael ; DeCarli, Charles. / Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative. In: Archives of Neurology. 2010 ; Vol. 67, No. 11. pp. 1370-1378.
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