This site uses cookies to measure how you use the website so it can be updated and improved based on your needs and also uses cookies to help remember the notifications you’ve seen, like this one, so that we don’t show them to you again. If you could also tell us a little bit about yourself, this information will help us understand how we can support you better and make this site even easier for you to use and navigate.

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, Beckett, Laurel, Jack, Clifford R., Jr., Weiner, Michael, DeCarli, Charles


Archives Of Neurology, Volume: 67, No.: 11, Pages.: 1370-1378

Year of Publication



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.;

Bibtex Citation

@article{Carmichael_2010, doi = {10.1001/archneurol.2010.284}, url = {}, year = 2010, month = {nov}, publisher = {American Medical Association ({AMA})}, volume = {67}, number = {11}, pages = {1370}, author = {Owen Carmichael}, title = {Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative}, journal = {Arch Neurol} }


aged, aged, 80 and over, alzheimer disease, atrophy, brain, cognition, female, humans, magnetic resonance imaging, male, nerve fibers myelinated, neuropsychological tests, organ size, pathology, physiology, physiopathology, regression analysis

Countries of Study


Types of Dementia

Alzheimer’s Disease

Type of Outcomes


Type of Interventions

Diagnostic Target Identification

Diagnostic Targets

Neuroimaging (e.g. MRI, PET, CAT etc.)