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Comparative Study
. 2008 Sep;65(9):1202-8.
doi: 10.1001/archneur.65.9.1202.

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

Adam M Brickman  1 , Lawrence S Honig, Nikolaos Scarmeas, Oksana Tatarina, Linda Sanders, Marilyn S Albert, Jason Brandt, Deborah Blacker, Yaakov Stern
Affiliations
Comparative Study

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

Adam M Brickman et al. Arch Neurol. 2008 Sep.

Abstract

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 (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -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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Conflict of interest statement

Disclosures: The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Bicaudate ratio. The yellow represents the distance between the two apices of the caudate nuclei. The inner skull dimension is shown in turquoise. The bicaudate ratio is derived by dividing the ventricular dimension (yellow) by the inner skull dimension (turquoise). A higher ratio represents greater atrophy.
Figure 2
Figure 2
Predicted rates of cognitive change based on baseline characterization of bicaudate ratio. For graphical presentation, baseline bicaudate ratio is presented as a dichotomous variable based on the median split of the entire sample (median=0.1567). Note that higher bicaudate ratio indicates greater amounts of atrophy. The results from the GEE analysis suggest that the greater the amount of atrophy at baseline, the greater the rate of cognitive decline.
Figure 3
Figure 3
Predicted rates of cognitive change based on baseline characterization of WMH severity. For graphical presentation, the baseline Scheltens Scale score is presented as a dichotomous variable based on the median split of the entire sample (median = 3.0). Note that higher “High WMH” refers to more severe WMH. The results from the GEE analysis suggest that the greater the more severe the baseline WMH, the greater the rate of cognitive decline.
Figure 4
Figure 4
Graphical representation of the significant Time by baseline WMH by baseline atrophy interaction. For the purpose of graphical presentation, WMH severity (circles and triangles) and degree of atrophy (upper and lower panel) are displayed in high and low groups based on the median severity. Note that the predicted mMMS scores decline most precipitously among individuals with greater level of atrophy and the greater baseline WMH burden (lower panel, circles).
See this image and copyright information in PMC

References

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