Yoshiyuki Hosokai

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

Dementia is one of the most debilitating symptoms of Parkinsons disease. A recent longitudinal study suggests that up to 80% of patients with Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons disease dementia.

Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment.

There is no consensus with regard to the clinical and neuroimaging characteristics of prodromal dementia in Parkinsons disease (PD). To delineate functional neuroimaging features of PD with mild cognitive impairment (PDMCI) and with no cognitive impairment (PDNC), we compared regional cerebral glucose metabolism (CMRglc) amongst 13 patients with PDMCI, 27 with PDNC, and 13 healthy controls. The PDNC patients had limited areas of hypometabolism in the frontal and occipital cortices. In the PDMCI patients, there were extensive areas of hypometabolism in the posterior cortical regions, including the temporo‐parieto‐occipital junction, medial parietal, and inferior temporal cortices. The present results suggest that posterior cortical dysfunction is the primary neuroimaging feature of PD patients at risk for dementia.

Association of olfactory dysfunction and brain. Metabolism in Parkinson's disease

Hyposmia is one of the cardinal early symptoms of Parkinson disease (PD). Accumulating clinical and pathological evidence suggests that dysfunction of the olfactory‐related cortices may be responsible for the impaired olfactory processing observed in PD; however, there are no clear data showing a direct association between altered brain metabolism and hyposmia in PD. In this study, we evaluated brain glucose metabolism and smell‐identification ability in 69 Japanese patients with nondemented PD. Olfactory function was assessed using the Odor Stick Identification Test for Japanese. The regional cerebral metabolic rate of glucose consumption at rest was measured using 18F‐fluorodeoxyglucose positron emission tomography and was analyzed using SPM‐based group comparisons and the brain–behavior partial least‐squares method. We found that olfactory dysfunction was closely related to cognitive dysfunction, including memory impairment. Moreover, brain–behavior partial least‐squares analysis revealed that odor‐identification performance was closely associated with broad cortical dysfunction, including dysfunction of the piriform cortex and amygdala. Our results suggest that the cognitive deficit in olfactory perception is an important aspect of hyposmia in PD and that this deficit is caused by altered brain metabolism in the amygdala and piriform cortex.

Corticolimbic gray matter loss in Parkinson’s disease without dementia

Background:  The relationship between corticolimbic involvement and cognitive dysfunction in non‐demented Parkinson’s disease (PD) patients has not yet been elucidated.

Do parkinsonian patients have trouble telling lies? The neurobiological basis of deceptive behaviour

Parkinsons disease is a common neurodegenerative disorder with both motor symptoms and cognitive deficits such as executive dysfunction. Over the past 100 years, a growing body of literature has suggested that patients with Parkinsons disease have characteristic personality traits such as industriousness, seriousness and inflexibility. They have also been described as ‘honest’, indicating that they have a tendency not to deceive others. However, these personality traits may actually be associated with dysfunction of specific brain regions affected by the disease. In the present study, we show that patients with Parkinsons disease are indeed ‘honest’, and that this personality trait might be derived from dysfunction of the prefrontal cortex. Using a novel cognitive task, we confirmed that patients with Parkinsons disease (n = 32) had difficulty making deceptive responses relative to healthy controls (n = 20). Also, using resting-state 18F-fluorodeoxyglucose PET, we showed that this difficulty was significantly correlated with prefrontal hypometabolism. Our results are the first to demonstrate that the ostensible honesty found in patients with Parkinsons disease has a neurobiological basis, and they provide direct neuropsychological evidence of the brain mechanisms crucial for human deceptive behaviour.

Attentional set-shifting deficit in Parkinson's disease is associated with prefrontal dysfunction: an FDG-PET study.

The attentional set-shifting deficit that has been observed in Parkinson’s disease (PD) has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients.

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

Prader‐Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age‐ and gender‐matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole‐brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel‐based morphometry. The PWS subjects showed small gray‐matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray‐matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas. Hum Brain Mapp, 2011.

Frontal-lobe syndrome and psychosis after damage to the brainstem dopaminergic nuclei

A patient developed frontal-lobe syndrome and psychotic symptoms after infarction in the pontomesencephalic junction. Stereotaxic lesion localization on magnetic resonance imaging and statistical analyses of regional cerebral blood flow (rCBF) disclosed an involvement of the rostral brainstem dopaminergic nuclei and hypoperfusion in the frontal-subcortical circuit components. We suggest that the patients cognitive and behavioral disturbances were associated with disruption of ascending dopaminergic projections to the frontal-subcortical circuits.

Diagnosis of drowning using post-mortem computed tomography based on the volume and density of fluid accumulation in the maxillary and sphenoid sinuses.

Recent studies have reported that drowning victims frequently have fluid accumulation in the paranasal sinuses, most notably the maxillary and sphenoid sinuses. However, in our previous study, many non-drowning victims also had fluid accumulation in the sinuses. Therefore, we evaluated the qualitative difference in fluid accumulation between drowning and non-drowning cases in the present study. Thirty-eight drowning and 73 non-drowning cases were investigated retrospectively. The fluid volume and density of each case were calculated using a DICOM workstation. The drowning cases were compared with the non-drowning cases using the Mann-Whitney U-test because the data showed non-normal distribution. The median fluid volume was 1.82 (range 0.02-11.7) ml in the drowning cases and 0.49 (0.03-8.7) ml in the non-drowning cases, and the median fluid density was 22 (-14 to 66) and 39 (-65 to 77) HU, respectively. Both volume and density differed significantly between the drowning and non-drowning cases (p=0.001, p=0.0007). Regarding cut-off levels in the ROC analysis, the points on the ROC curve closest (0, 1) were 1.03ml (sensitivity 68%, specificity 68%, PPV 53%, NPV 81%) and 27.5 HU (61%, 70%, 51%, 77%). The Youden indices were 1.03ml and 37.8 HU (84%, 51%, 47%, 86%). When the cut-off level was set at 1.03ml and 27.5HU, the sensitivity was 42%, specificity 45%, PPV 29% and NPV 60%. When the cut-off level was set at 1.03ml and 37.8HU, sensitivity was 58%, specificity 32%, PPV 31% and NPV 59%.

Synthesis of Gd2O3 nanoparticles for MRI contrast agents

Gd2O3 nanoparticles were synthesized by using our original method for application as MRI contrast agents. The sample diameters were controlled in the range 18–66 nm by adjusting the annealing temperature between 773 and 1273 K in air or in an Ar atmosphere. Magnetization measurements were performed at 300 K, and the effective magnetic moment of each sample was calculated. They showed paramagnetism at 300 K and they had large effective magnetic moment μeff of 7.15–8.05 μB. MRI measurements were performed in 0.8 wt% agarose solution, and the Gd2O3 nanoparticles were found to work as effective T1-shortening MRI contrast agents.