Shoki Takahashi

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.

Relationship Between Fluoroscopic Time, Dose–Area Product, Body Weight, and Maximum Radiation Skin Dose in Cardiac Interventional Procedures

OBJECTIVE Real-time maximum dose monitoring of the skin is unavailable on many of the X-ray machines that are used for cardiac intervention procedures. Therefore, some reports have recommended that physicians record the fluoroscopic time for patients undergoing fluoroscopically guided intervention procedures. However, the relationship between the fluoroscopic time and the maximum radiation skin dose is not clear. This article describes the correlation between the maximum radiation skin dose and fluoroscopic time for patients undergoing cardiac intervention procedures. In addition, we examined whether the correlations between maximum radiation skin dose and body weight, fluoroscopic time, and dose-area product (DAP) were useful for estimating the maximum skin dose during cardiac intervention procedures. MATERIALS AND METHODS Two hundred consecutive cardiac intervention procedures were studied: 172 percutaneous coronary interventions and 28 cardiac radiofrequency catheter ablation (RFCA) procedures. The patient skin dose and DAP were measured using Caregraph with skin-dose-mapping software. RESULTS For the RFCA procedures, we found a good correlation between the maximum radiation skin dose and fluoroscopic time (r = 0.801, p < 0.0001), whereas we found a poor correlation between the maximum radiation skin dose and fluoroscopic time for the percutaneous coronary intervention procedures (r = 0.628, p < 0.0001). There was a strong correlation between the maximum radiation skin dose and DAP in RFCA procedures (r = 0.942, p < 0.0001). There was also a significant correlation between the maximum radiation skin dose and DAP (r = 0.724, p < 0.0001) and weight-fluoroscopic time product (WFP) (r = 0.709, p < 0.0001) in percutaneous coronary intervention procedures. CONCLUSION The correlation between the maximum radiation skin dose with DAP is more striking than that with fluoroscopic time in both RFCA and percutaneous coronary intervention procedures. We recommend that physicians record the DAP when it can be monitored and that physicians record the fluoroscopic time when DAP cannot be monitored for estimating the maximum patient skin dose in RFCA procedures. For estimating the maximum patient skin dose in percutaneous coronary intervention procedures, we also recommend that physicians record DAP when it can be monitored and that physicians record WFP when DAP cannot be monitored.

Neural Basis of the Retrieval of People's Names: Evidence from Brain-Damaged Patients and fMRI

The aim of this study was to identify the neuroanatomical basis of the retrieval of peoples names. Lesion data showed that patients with language-dominant temporal lobectomy had impairments in their ability to retrieve familiar and newly learned peoples names, whereas patients with language-nondominant temporal lobectomy had difficulty retrieving newly learned peoples names. Functional magnetic resonance imaging experiments revealed activations in the left temporal polar region during the retrieval of familiar and newly learned peoples names, and in the right superior temporal and bilateral prefrontal cortices during the retrieval of newly learned information from face cues. These data provide new evidence that the left anterior temporal region is crucial for the retrieval of peoples names irrespective of their familiarity and that the right superior temporal and bilateral prefrontal areas are crucial for the process of associating newly learned peoples faces and names.

MRI of Cardiac Sarcoidosis: Basal and Subepicardial Localization of Myocardial Lesions and Their Effect on Left Ventricular Function

OBJECTIVE The objective of our study was to use MRI to analyze the topographic localization of myocardial lesions and their relationship to plasma brain natriuretic peptide (BNP) levels and several cardiac function parameters in patients with cardiac sarcoidosis. MATERIALS AND METHODS Delayed contrast-enhanced MRI was performed in 40 patients with sarcoidosis (11 cardiac, 29 extracardiac cases). Using a 29-segment model of the left ventricle (LV), the extent of myocardial hyperenhancement was visually scored (0 = no hyperenhancement, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100% hyperenhancement) and was compared with plasma BNP level and several parameters of cardiac function. RESULTS Ten of the 11 patients with cardiac sarcoidosis showed myocardial hyperenhancement, whereas none of the 29 patients without cardiac sarcoidosis did. In patients with cardiac sarcoidosis, hyperenhancement was significantly more extensive in basal short axis slices than in apical short axis slices (p < 0.0005). Myocardial hyperenhancement was significantly more frequent in subepicardial layers than in subendocardial layers. The global extent of myocardial hyperenhancement was significantly correlated with plasma BNP levels and the LV end-diastolic volume index and was negatively correlated with the LV ejection fraction. CONCLUSION In patients with cardiac sarcoidosis, myocardial lesions detected on delayed contrast-enhanced MRI were predominantly localized in the basal and subepicardial myocardium. The extent of myocardial lesions may be related to LV dysfunction and plasma BNP level in patients with cardiac sarcoidosis.

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.

Neural Basis of Temporal Context Memory: A Functional MRI Study

Temporal context information is crucial to understanding human episodic memory. Human lesion and neuroimaging data indicate that prefrontal regions are important for retrieving temporal context memory, although the exact nature of their involvement is still unclear. We employed functional magnetic resonance imaging (fMRI) to elucidate the neural basis of two kinds of temporal context memory: the temporal order of items between lists and within a list. On the day of the fMRI experiment, subjects memorized a list of 30 pictures in the morning and another list of 30 pictures in the afternoon. During the scanning session, the subjects performed three tasks. In a between-lists task, they were asked to judge the temporal order between two items that had been presented in different lists. In a within-list task, they were asked to judge the temporal order between two items that had been presented in a single list. We found bilateral prefrontal activities during these two temporal context memory tasks compared with a simple item-recognition task. Furthermore, in direct comparison between these two tasks, we found differential prefrontal activities. Thus, right prefrontal activity was associated with temporal order judgment of items between lists, whereas left prefrontal activity was related to temporal order judgment of items within a list. These results indicate that retrieval processes of two kinds of temporal context memory are supported by different, but overlapping, sets of cerebral regions. We speculate that this reflects different cognitive processes for retrieving temporal context memory between separate episodes and within a single episode.

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

WE used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

In vivo visualization of α-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy

The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.

Usefulness of contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions in detection of small brain metastasis at 3T MR imaging: comparison with magnetization-prepared rapid acquisition of gradient echo imaging.

BACKGROUND AND PURPOSE: Early accurate diagnosis of brain metastases is crucial for a patients prognosis. This study aimed to compare the conspicuity and detectability of small brain metastases between contrast-enhanced 3D fast spin-echo (sampling perfection with application-optimized contrasts by using different flip angle evolutions [SPACE]) and 3D gradient-echo (GE) T1-weighted (magnetization-prepared rapid acquisition of GE [MPRAGE]) images at 3T. MATERIALS AND METHODS: Sixty-nine consecutive patients with suspected brain metastases were evaluated prospectively by using SPACE and MPRAGE on a 3T MR imaging system. After careful evaluation by 2 experienced neuroradiologists, 92 lesions from 16 patients were selected as brain metastases. We compared the shorter diameter, contrast rate (CR), and contrast-to-noise ratio (CNR) of each lesion. Diagnostic ability was compared by using receiver operating characteristic (ROC) analysis. Ten radiologists (5 neuroradiologists and 5 residents) participated in the reading. RESULTS: The mean diameter was significantly larger by using SPACE than MPRAGE (mean, 4.5 ± 3.7 versus 4.3 ± 3.7 mm, P = .0014). The CR and CNR of SPACE (mean, 57.3 ± 47.4%, 3.0 ± 1.9, respectively) were significantly higher than those of MPRAGE (mean, 37.9 ± 41.2%, 2.6 ± 2.2; P < .0001, P = .04). The mean area under the ROC curve was significantly larger with SPACE than with MPRAGE (neuroradiologists, 0.99 versus 0.88, P = .013; residents, 0.99 versus 0.78, P = .0001). CONCLUSIONS: Lesion detectability was significantly higher on SPACE than on MPRAGE, irrespective of the experience of the reader in neuroradiology. SPACE should be a promising diagnostic technique for assessing brain metastases.

Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cells.

Transcription factor Ets‐1 is induced in endothelial cells (ECs) by angiogenic factors, and promotes angiogenesis by inducing angiogenesis‐related genes such as MMPs and integrin β3. Here, we examined the effect of Ets‐1 on apoptosis in ECs. Overexpression of Ets‐1 in human umbilical vein endothelial cells (HUVECs) induced apoptosis under the serum‐deprived condition. VEGF inhibited apoptosis and augmented the DNA binding of Ets‐1 in HUVECs. The inhibition of transcriptional activity of endogenous Ets‐1 by a dominant negative molecule intensified the anti‐apoptotic effect of VEGF. Caspase inhibitors blocked apoptosis of HUVECs induced by Ets‐1. DNA array analysis showed that Ets‐1 up‐regulated pro‐apoptotic genes such as Bid, cytochrome p450, caspase‐4, p27, and p21 more than 2 fold, and down‐regualted anti‐apoptotic genes such as DAD‐1, AXL, Cox‐2, IAP‐2, and MDM‐2 less than 0.5 fold in HUVECs. These results indicate that Ets‐1 itself is pro‐apoptotic to ECs by modulating the expression of apoptosis‐related genes.