Objectives: The mechanism underlying olfactory dysfunction in Parkinson's disease (PD) remains unknown. The current study aims to investigate the relationship between sequential changes of volume change of cortex associated with olfactory function and degree of deficiency of olfactory performance in PD. Methods: Based on the arbitrary cut-off score of olfactory performance measured by 'five odors olfactory detection arrays', subjects were classified into three groups: PD patients with olfactory impairment (OPD, n = 12), PD without olfactory impairment (NPD, n = 14), and healthy controls without olfactory impairment (NC, n = 26). A morphometric analysis of magnetic resonance images (voxel-based morphometry; VBM) was used to investigate cortical volume change. Results: The scores of olfactory performance were higher in both NPD and OPD groups than in the NC group independent of age and disease duration, indicating that NPD subjects did have board line deficiency of olfaction though not meet the cut-off score for abnormal olfactory function. Both NPD and OPD had cortical atrophy in the parahippocampal gyrus (PCG), but only OPD also had change in orbitofrontal cortex (OFC). Correlation analysis revealed that decrement of volumes of PCG and right OFC was associated with decreased olfactory detection sensitivity, and the right OFC was also correlated to olfactory identification. However, no correlation was found between structural changes and the severity of the disease measured by UPDRS score. Conclusions: The results confirmed that atrophy in piriform cortex and orbitofrontal cortex is associated with olfactory dysfunction in early PD. Atrophy of the orbitofrontal cortex becomes significant as olfactory damage progresses. Volume measurement of olfaction-associated areas together with the assessment of olfactory function may be a sensitive indicator for the early diagnosis of PD. Copyright (C) 2011 S. Karger AG, Basel