A 49-year-old woman presented with progressive dementia. Diffusion-weighted MR images showed abnormalities in the cerebral cortex as well as the putamen and caudate head bilaterally. MR spectroscopic imaging revealed marked asymmetric decrease of normal metabolites in the right basal ganglia, with concordant hypoperfusion on single photon emission computed tomography. Diffusion-weighted MR imaging is more sensitive to cortical involvement in sporadic Creutzfeldt-Jakob Disease, and MR spectroscopy may yield evidence of asymmetric involvement. Combined functional and metabolic MR imaging may be useful in studying CJD.