Title

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

Document Type

Article

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, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), 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.

Medical Subject Headings

Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Cognition; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Neuropsychological Tests; Organ Size; Regression Analysis

Publication Date

11-1-2010

Publication Title

Archives of neurology

ISSN

1538-3687

Volume

67

Issue

11

First Page

1370

Last Page

1378

PubMed ID

21060014

Digital Object Identifier (DOI)

10.1001/archneurol.2010.284

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