Kazumi Hirayama

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.

Does the Human Dorsal Stream Really Process a Category for Tools

Previously, Almeida et al. (2008) used a technique called Continuous Flash Suppression to show that human dorsal stream cortical areas specifically responded to a “tool category.” Here, we used the same technique to clarify what attributes of tools are processed in the dorsal stream. We examined surface attributes and shape. A significant priming effect was found when we removed surface attributes by using line drawings instead of photographs. In a second experiment, we manipulated shape and we found that there were no significant priming effects when we used nonelongated tool pictures as tool prime stimuli. To better clarify the effect of shape attributes on priming effects, we conducted a further experiment using elongated stick-like rectangles as prime stimuli and found that elongated shapes significantly shortened the reaction time to the tool pictures as target stimuli. Additionally, when elongated vegetables were used as prime stimuli, the reaction time to the tool pictures as target stimuli was also significantly shortened, but there was no effect when stubby vegetables were used. Finally, when we controlled for orientation by presenting rotated elongated stick-like rectangles, diamond shapes, and cut circles as prime stimuli, we found that rectangles replicated the same significant priming effect as previous experiments, but the others did not. These results suggest that the dorsal stream processes elongated shapes but does not process the tool category specifically.

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.

Reactivation of medial temporal lobe and occipital lobe during the retrieval of color information: A positron emission tomography study.

It is widely accepted that memory traces of an event include various types of information about the content of the event and about the circumstances in which the individual experienced it. However, how these various types of information are stored and later retrieved is poorly understood. One hypothesis postulates that the retrieval of specific event information reactivates regions that were active during the encoding of this information, with the aid of binding functions of the medial temporal lobe (MTL) structures. We used positron emission tomography to identify the brain regions related to the encoding and retrieval of color information. Specifically, we assessed whether overlapping activity was found in both the MTL structures and color-related cortical regions during the encoding and retrieval of color information attached with meaningless shapes. During the study, subjects were asked to encode colored (red or green) and achromatic random shapes. At subsequent testing, subjects were presented with only achromatic shapes, which had been presented with or without colors during encoding, and were engaged in retrieval tasks of shapes and colors. Overlapping activity was found in the MTL and occipital lobe (the lingual and inferior occipital gyri) in the right hemisphere during the encoding and retrieval of meaningless shapes with color information compared with those without color information. Although there are some limitations to be considered, the present findings seem to support the view that the retrieval of specific event information is associated with reactivation of both the MTL structures and the regions involved during encoding of the information.

Visual Agnosia for Line Drawings and Silhouettes without Apparent Impairment of Real-Object Recognition: A Case Report

We report on a patient with visual agnosia for line drawings and silhouette pictures following cerebral infarction in the region of the right posterior cerebral artery. The patient retained the ability to recognize real objects and their photographs, and could precisely copy line drawings of objects that she could not name. This case report highlights the importance of clinicians and researchers paying special attention to avoid overlooking agnosia in such cases. The factors that lead to problems in the identification of stimuli other than real objects in agnosic cases are discussed.

Neural Substrates of Cognitive Subtypes in Parkinson's Disease: A 3-Year Longitudinal Study

Background The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinsons disease (PD) remain to be elucidated. Methods Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography. Results Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease. Conclusions These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.