Journal of Alzheimer’s Disease 9 (2006) 253–260 253 IOS Press Relationship of cognitive measures and gray and white matter in Alzheimer’s disease Leslie C. Baxter a,∗ , D. Larry Sparks b , Sterling C. Johnson c , Brian Lenoski a , Jean E. Lopez b , Donald J. Connor b and Marwan N. Sabbagh b a Barrow Neurological Institute, Phoenix, AZ, USA b Sun Health Research Institute, Sun City, AZ, USA c University of Wisconsin-Madison, Madison, WI, USA Abstract. Objective: To examine the relationship between commonly used screening cognitive measures with gray and white matter integrity in patients with mild to moderate AD. Background: New neuroimaging techniques, such as voxel-based morphometry (VBM), make it possible to study the relationship between structural brain integrity and cognitive functioning in AD. Methods: Gray and white matter integrity was evaluated using VBM in fifteen patients with mild to moderate AD. ADAS-Cog and MMSE scores were also performed as part of the baseline assessment for a larger clinical trial in the AD patients. Correlations between cognitive measures and VBM were performed. Results: Both the ADAS-Cog and the MMSE showed a similar relationship with gray matter degeneration, reflecting greater cognitive impairment with decreased gray matter in the left temporal lobe. However, the MMSE score was much more reflective of underlying white matter changes than ADAS-Cog scores, particularly in frontotemporal region. These findings suggest that the ADAS-Cog and MMSE reflect different aspects of the underlying brain changes observed in AD. The ADAS-Cog was more specific to gray matter integrity whereas the MMSE reflected a more global reduction in both gray and white matter. Conclusions: These results support using neuroimaging markers of neural integrity as an important consideration when evaluating treatment efficacy. Furthermore, whole-brain analyses such as VBM help to evaluate neural systems that are not necessarily targeted by the treatment. Keywords: Alzheimer’s disease, voxel based morphometry, ADAS-Cog, MMSE 1. Introduction Cognitive measures such as the Alzheimer’s Dis- ease Assessment Scale- Cognitive subtest (ADAS-Cog) and Mini Mental State Examination (MMSE) are com- monly used for categorization and treatment efficacy in AD. MRI is used primarily as a diagnostic tool to rule out conditions other than AD. However, MRI is becom- ing more useful in understanding whether cognitive im- pairment in AD is associated with general or specific * Corresponding author: Leslie C. Baxter, Ph.D., Neuropsy- chology Neuroimaging Laboratory, Barrow Neurological Institute, Phoenix, AZ 85013, USA. Tel.: +1 602 406 6706; Fax: +1 602 406 3498; E-mail: leslie.baxter@chw.edu. effects of the disease process. Volumetric changes ob- served with MRI in the hippocampal region have been correlated to disease progression [8,9] and predict de- velopment of AD in individuals with memory impair- ment [12] suggesting that neuroimaging quantification may serve as a useful measure of brain integrity in AD patients. New voxel-wise brain mapping techniques such as voxel-based morphometry (VBM) allow for quantita- tive assessment of structural brain integrity. This tech- nique circumvents some of the problems encountered with previous morphometric techniques, including pos- sible measurement bias and the limitations of speci- fying regions of interest [1]. Quantitative assessment of gray matter concentration (GMC) is a measure of VBM that may be particularly helpful in detecting and ISSN 1387-2877/06/$17.00  2006 – IOS Press and the authors. All rights reserved