title: Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson's disease: a 3 year longitudinal study.
abstract: Dementia is one of the most debilitating symptoms of Parkinson's disease. A recent longitudinal study suggests that up to 80% of patients with Parkinson's disease will eventually develop dementia. Despite its clinical importance, the development of dementia is still difficult to predict at early stages. We previously identified olfactory dysfunction as one of the most important indicators of cortical hypometabolism in Parkinson's disease. In this study, we investigated the possible associations between olfactory dysfunction and the risk of developing dementia within a 3-year observation period. Forty-four patients with Parkinson's disease without dementia underwent the odour stick identification test for Japanese, memory and visuoperceptual assessments, (18)F-fluorodeoxyglucose positron emission tomography scans and magnetic resonance imaging scans at baseline and 3 years later. A subgroup of patients with Parkinson's disease who exhibited severe hyposmia at baseline showed more pronounced cognitive decline at the follow-up survey. By the end of the study, 10 of 44 patients with Parkinson's disease had developed dementia, all of whom had severe hyposmia at baseline. The 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 the score of odour stick identification test for Japanese. We also found an association between severe hyposmia and a characteristic distribution of cerebral metabolic decline, which was identical to that of dementia associated with Parkinson's disease. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and the atrophy of focal brain structures, including the amygdala and other limbic structures. Together, 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 Parkinson's disease dementia.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Baba
authors.forename: Akio
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Hirayama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nishio
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hosokai
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kanno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Sugeno
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Konno
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Shoki
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000150:complications* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009812:Odorants; D000857:Olfaction Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D011877:Radionuclide Imaging