- Objective: This 12-week study of two elderly, depressed subjects investigated the effect of acetyl-L-carnitine (ALCAR) treatment on the Hamilton Depression Rating Scale (HDRS) and on measures of high-energy phosphate and membrane phospholipid metabolism. Methods: Two mildly depressed (HDRS 15–20), non-demented male subjects 70 and 80 years old were compared with six non-demented controls (all males, mean age of 73.6 ± 3.6 years). High-energy and membrane phospholipid metabolites were measured by phosphorus magnetic resonance spectroscopic imaging (31P MRSI) analysis. HDRS and 31P MRSI measurements were taken at entry, 6 and 12 weeks for the depressed subjects. Results: 31P MRSI analysis revealed elevated levels of phosphomonesters [PME(s – τc)] in the prefrontal region of these mildly depressed subjects, which decreased with ALCAR treatment and showed a trend for correlation of the PME(s – τc) levels with HDRS. ALCAR treatment also resulted in increasing levels of the prefrontal phosphocreatine (PCr), which correlated with HDRS. Conclusions: In the prefrontal region, the mildly depressed subjects compared with controls had elevated PME(s – τc) levels which normalized after 12 weeks of ALCAR and increased PCr levels after ALCAR treatment. These preliminary findings suggest further studies are warranted.