Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Twodimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.