Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson's disease: A 3 year longitudinal study

Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Brain (Impact Factor: 9.2). 01/2012; 135(Pt 1):161-9. DOI: 10.1093/brain/awr321
Source: PubMed


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.

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Available from: Takafumi Hasegawa
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    • "The longitudinal/time-dependent progression of regional brain atrophy in PD patients has been investigated in relatively few MR studies, with conflicting results. For instance, previous papers have described gray matter (GM) loss in limbic-paralimbic structures in non-demented PD patients and neocortical changes in PD patients (Ram ırez-Ruiz et al., 2005), widespread limbic, paralimbic, and neocortical greymatter loss in PD patients with visual hallucinations (Ibarretxe-Bilbao et al., 2010), volume reduction in amygdala and temporal cortex in PD patients without severe hyposmia and (conversely) only sparse longitudinal volume changes in patients with hyposmia (Baba et al., 2012), progressive amigdalar atrophy and cortical thinning in frontotemporal regions in the early stages of the disease (Ibarretxe-Bilbao et al., 2012), and greater progression of cortical thinning in frontal, limbic, and posterior cortical regions in advanced PD patients that converted to dementia with respect to non-converters (Compta et al., 2013), whereas others reported no differences in regional brain atrophy rates between PD patients and healthy controls (Brenneis et al., 2003). Also, some longitudinal MR studies employed measures of global atrophy in order to monitor the progression of the degenerative process in PD. "
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    • "All data entry and analyses were performed using SPSS Windows 17.0. Student's t-tests and chi-square tests (to test for diagnosis and sex differences) were used to compare the demographic variables, neuropsychological measures, and cognitive performance scores between the subjects with severe hyposmia (OE test ≤ 4) and those without severe hyposmia (OE test ≥ 5) (Baba et al. 2012). Pearson correlation coefficients were calculated to assess simple relationships between OE test score and cognitive test performance . "
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