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Axonal injury within language network in primary progressive aphasia

Primary progressive aphasia (PPA) is characterized by an isolated progressive impairment of word use and comprehension reflecting the distribution of pathological processes within the left hemisphere. We used proton magnetic resonance spectroscopy (1H‐MRS) to study in vivo the integrity of axonal fibers connecting perisylvian language areas in 11 patients with PPA, 11 subjects with Alzheimer's disease, and 22 controls. Brain metabolites (N‐acetylaspartate, myoinositol, choline, creatine) were measured bilaterally within a volume of interest located in the central portion of the superior longitudinal fasciculus, a long associative bundle connecting Broca's area with Wernicke's area, and other language regions of the temporal lobe. In the PPA group, there was an asymmetrical N‐acetylaspartate to creatine ratio reduction compared with Alzheimer's disease and controls, with greater changes on the left side. The myoinositol to creatine ratio was increased in the PPA group bilaterally compared with controls. The choline to creatine ratio did not differ among the three groups. These results indicate an asymmetrical focal axonal injury within the language network in PPA. The marked difference in the distribution of N‐acetylaspartate to creatine between PPA and Alzheimer's disease suggests that proton magnetic resonance spectroscopy may help to differentiate between these two conditions. Ann Neurol 2003;53:000–000