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Adam M. Brickman, PhD; Lawrence S. Honig, MD, PhD; Nikolaos Scarmeas, MD; Oksana Tatarina, BA; Linda Sanders, BA; Marilyn S. Albert, PhD; Jason Brandt, PhD; Deborah Blacker, MD, ScD; Yaakov Stern, PhD

Arch Neurol. 2008;65(9):1202-1208.

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.

Author Affiliations: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University (Drs Brickman, Honig, Scarmeas, and Stern and Mss Tatarina and Sanders); and Department of Neurology, Columbia University Medical Center (Drs Brickman, Honig, Scarmeas, and Stern), New York, New York; Departments of Neurology (Drs Albert and Brandt) and Psychiatry and Behavioral Sciences (Dr Brandt), The Johns Hopkins University, Baltimore, Maryland; and Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (Dr Blacker).

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