Olfactory dysfunction and dementia in Parkinson's disease

Dementia is one of the most debilitating symptoms of Parkinson's disease (PD), but the development of dementia is still difficult to predict at early stages of the disease. We recently found that hyposmia, one of the most typical non-motor features of PD, was a predictive feature of Parkinson's disease with dementia (PDD). In that work, multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in scores on the odor stick identification test for Japanese (OSIT-J). We also found an association between severe hyposmia and a specific pattern of cerebral metabolic decline, which was identical to findings observed in PDD. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and atrophy of focal brain structures, including the amygdala and other limbic structures. Our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of PDD. We have now started a randomized, double-blind study using donepezil for the PD group with severe hyposmia. We hope that this clinical trial will allow us to establish a therapeutic intervention that can improve the prognosis of advanced PD.