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, Sep 30, 2015
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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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    ABSTRACT: The presence of brain atrophy and its progression in early Parkinson's disease (PD) are still a matter of debate, particularly in patients without cognitive impairment. The aim of this longitudinal study was to assess whether PD patients who remain cognitively intact develop progressive atrophic changes in the early stages of the disease. For this purpose, we employed high-resolution T1-weighted MR imaging to compare 22 drug-naïve de novo PD patients without cognitive impairment to 17 age-matched control subjects, both at baseline and at three-year follow-up. We used tensor-based morphometry to explore the presence of atrophic changes at baseline and to compute yearly atrophy rates, after which we performed voxel-wise group comparisons using threshold-free cluster enhancement. At baseline, we did not observe significant differences in regional atrophy in PD patients with respect to control subjects. In contrast, PD patients showed significantly higher yearly atrophy rates in the prefrontal cortex, anterior cingulum, caudate nucleus, and thalamus when compared to control subjects. Our results indicate that even cognitively preserved PD patients show progressive cortical and subcortical atrophic changes in regions related to cognitive functions and that these changes are already detectable in the early stages of the disease. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2014; 35(8). DOI:10.1002/hbm.22449 · 5.97 Impact Factor
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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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    ABSTRACT: Olfactory impairment constitutes one of the earliest signs of Alzheimer's disease in older adults with mild cognitive impairment. We investigated which aspects of neuropsychological measures are correlated with olfactory identification performance among older adults with mild cognitive impairment. Total of 220 participants with mild cognitive impairment (mean age 71.7 years) were examined. Odor identification was assessed using the Open Essence test. Participants underwent comprehensive neurocognitive evaluation, including measures of verbal memory, visual memory, working memory, attention/executive function, and processing speed. We examined associations between olfactory function and cognitive performance scores. Participants with severe hyposmia exhibited significantly poor verbal and visual memory performance, attention/executive function, and slower processing speed scores compared with those without severe hyposmia. In multivariable logistic regression models, better performance scores on verbal and visual memory were significantly associated with decreased likelihood of severe hyposmia after adjusting for age, sex, education, and other cognitive performance scores. These findings suggest that olfactory impairment might be more closely associated with memory loss compared with other aspects of cognitive functioning in mild cognitive impairment subjects.
    Chemical Senses 11/2013; 39(1). DOI:10.1093/chemse/bjt052 · 3.16 Impact Factor
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    • "One recent study found severe hyposmia as a risk factor for development of dementia within 3 years in PD patients [41]. In the same study, MR volumetric studies showed close relationships between olfactory dysfunction and the atrophy of focal brain structures including the amygdala [41]. In addition, hyposmia has been found to be a common feature of spino-cerebellar ataxias [42]. "
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    ABSTRACT: The piriform cortex and cortical amygdala (PCA) and the orbitofrontal cortex (OFC) are considered olfactory-related brain regions. This study aims to elucidate the normal volumes of PCA and OFC of each age groups (20.0-70.0 year old), and whether the volumes of PCA and OFC decline with increasing age and diminishing olfactory function. One hundred and eleven healthy right-handed participants (54 males, 57 females), age 20.0 to 70.0 years were recruited to join this study after excluding all the major causes of olfactory dysfunction. Volumetric measurements of PCA and OFC were performed using consecutive 1-mm thick coronal slices of high-resolution 3-D MRIs. A validated olfactory function test (Sniffin' Sticks) assessed olfactory function, which measured odor threshold (THD), odor discrimination (DIS), and odor identification (ID) as well as their sum score (TDI). The volume of OFC decreased with age and significantly correlated with age-related declines in olfactory function. The volume of OFC showed significant age-group differences, particularly after 40 years old (p < 0.001), while olfactory function decreased significantly after 60 years old (p < 0.001). Similar age-related volumetric changes were not found for PCA (p = 0.772). Additionally, there was significant correlation between OFC and DIS on the Right Side (p = 0.028) and between OFC and TDI on both sides (p < 0.05). There was no similar correlation for PCA. Aging can have a great impact on the volume of OFC and olfactory function while it has much smaller effect on the volume of PCA. The result could be useful to establish normal volumes of PCA and OFC of each age group to assess neurological disorders that affect olfactory function.
    PLoS ONE 09/2013; 8(9):e74526. DOI:10.1371/journal.pone.0074526 · 3.23 Impact Factor
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