A Preclinical Risk Marker for Alzheimer’s Disease by Functional MRI

Shi-Jiang Li, Ph.D.

Medical College of Wisconsin , Milwaukee, WI

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

November 2001, for 3 years

Funding Amount:


Investigator Biographies

Shi-Jiang Li, Ph.D.

Associate Professor, Biophysics Research Institute, Medical College of Wisconsin



A newly developed functional MRI (fMRI) index to quantify the abnormality of functional synchrony in the human hippocampus is an early and sensitive biological marker to characterize the preclinical abnormality of Alzheimer's disease (AD).

To develop and validate an early, non-invasive, quantitative marker for the preclinical stage of Alzheimer's disease (risk marker) using fMRI. Such a sensitive marker for AD will have significant advantages in identifying people at risk, facilitating early assessment, and providing effective disease management.

To establish a preclinical marker for Alzheimer's, the researchers will conduct a longitudinal study of subjects with mild cognitive impairment (MCI) to determine who does and does not develop Alzheimer's during a three-year study. At the same time, we will determine the longitudinal change in the COSLOF index in their hippocampus regions. The researchers chose to study MCI subjects because of their high incidence (yearly 12-15%) of Alzheimer's development. At the end of the three-year period, we can look back to determine how well the COSLOF index predicted the preclinical onset of Alzheimer's and distinguished those subjects who were destined to develop Alzheimer's from those who were undergoing normal aging processes.

Selected Publications

Xu, G., Xu, Y., Wu, G., Antuono, P.G., Hammeke, T.A., and Li, S.-J.. Task-modulation of functional synchrony between spontaneous low-frequency oscillations in the human brain detected by fMRI.   Magn Reson Med, Jul 56(1):41-50 (2006).

Wu, G. and Li, S.-J.  Theoretical Noise Model for Oxygenation-sensitive MRI.  Magn Reson Med, 53, 1046-1054 (2005).

LI, S.-J., Li Z, Wu G, Zhang M, Franczak M, Antuono P. Alzheimer Disease: Evaluation of a functional MR imaging index as a marker.   Radiology, 225:253-259 (2002).

Li Z., Zhao X., Wu G., Luo F., Li S-J. (2002). “A multi-Echo Segmented EPI with Z-Shimmed Background Gradient Compensation Pulse (MESBAC) for fMRI Study.” Magnetic Resonance in Medicine.

Antuono P., Jones J., Wang Y., Li S-J. (2001). “Decreased glutamate + glutamine in Alzheimer’s disease detected in vivo with 1H-MRS at 0.5T.” Neurology, 56(6): 737-742.

Li S-J. (2001). “Reducing cardiac noise in BOLD-weighted voxel time courses in a fMRI dataset by increasing TR and/or applying a crusher gradient in an EPI acquisition pulse.” Magnetic Resonance in Medicine, 46: 629.

Zhao X., Bodurka J., Jesmanowicz A., Li, S-J. (2000). “BO-Fluctuation-Induced Temporal Variation in EPI Image Series Due to the Disturbance of Steady-State Free Precession.” Magnetic Resonance in Medicine, 44: 758-765.