Measuring cerebral atrophy and white matter hyperintensity burden to predict the rate of cognitive decline in Alzheimer disease

Brickman, Adam M.; Honig, Lawrence S.; Scarmeas, Nikolaos; Tatarina-Nulman, Oksana; Sanders, Linda; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Stern, Yaakov

Objective: To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD). Design: Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits. Setting: Three university-based AD centers in the United States. Participants: At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure: The mMMS score. Results: Generalized estimating equation models demonstrated that the degree of baseline atrophy (β = −0.316; P = .04), the severity of WMH (β = −0.173; P = .03), and their interaction (β = −6.061; P = .02) predicted the rate of decline in mMMS scores. Conclusions: Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD.


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Taub Institute
American Medical Association
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January 28, 2016