Olfactory impairment predicts brain atrophy in Parkinson's disease.

Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients (n = 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients (n = 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls (n = 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.