Akihiko Iida’s research while affiliated with Nagoya City University and other places

Objective: To examine the effect of apolipoprotein E (APOE) ɛ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and β-amyloid accumulation in the early stages of the Alzheimer's continuum. Methods: In this single-centre observational prospective cohort study, 24 APOE ɛ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. Results: The BBB kw values in the neocortices differed significantly among the groups (APOE ɛ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to -0.239, p=0.017), β-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to -0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ɛ4 dose. Interpretation: Our results suggest that an increased APOE ɛ4 dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.

Objective To investigate the mechanisms underlying the effect of repetitive transcranial magnetic stimulation (rTMS) on post-stroke hemiplegia, we assessed alterations in cerebral glucose metabolism.Methods Five post-stroke hemiplegic patients (three targeted for upper limb impairment and two targeted for lower limb impairment) aged 62.6 ± 6.1 years (mean ± standard deviation) with a duration since stroke onset of 3.5 ± 3.8 years participated in this preliminary study. Cerebral glucose metabolism was measured twice—before and after rTMS with intensive rehabilitation—using positron emission tomography with [18F]fluorodeoxyglucose. The Asymmetry Index (AI) was calculated to assess laterality of metabolism between the lesional and contralesional motor areas. The alteration rates of AI (%ΔAI) were compared between participants in whom rTMS was effective and ineffective.ResultsTwo of the three upper-limb-targeted patients and one of the two lower-limb-targeted patients showed motor function improvements following rTMS treatment. All three patients who responded to rTMS had improved laterality of cerebral glucose metabolism in motor areas, commonly in the precentral gyrus, with an %ΔAI of approximately 10%. In contrast, the two patients who did not respond to rTMS had no improvements in laterality.Conclusions These results suggest for the first time that improved glucose metabolism is associated with improved motor function after a combination of rTMS and intensive rehabilitation.

Purpose: We developed and validated the accuracy of a method to calculate the arterial input function (AIF) from PET images only, without the need for the arterial blood sampling, in the absolute quantitation of functional parametric values in 15O- gas PET examinations. Methods: We extended the method reported by Iguchi et al. (2013) to derive the arterial input function, thus absolute quantitative functional parametric images of cerebral perfusion and oxygen metabolism by a reference tissue approach. We compared shapes of the AIF and reproducibility of the absolute functional values. Existing test data that were carried out with the continuous arterial blood sampling were used for this study. Results: The estimated AIF shapes agreed well with those estimated from the continuous arterial blood sampling. The error range of the absolute quantitative values was approximately ±20%, with a fairly well reproducibility in the relative values being less than 3%. Conclusion: The AIFs by this method were reproducible. Although the absolute quantitative values varied depending on the assumed functional values in the reference region in individual cases, the relative images showed fairly good agreement with the results from the standard technique that employed the arterial blood sampling. The present technique may provide significant contribution to clinical examination.

Background Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly described in patients with genetically confirmed SCA6.Methods We conducted a positron emission tomography study using a combination of [18F]fluoro-l-dopa for dopamine synthesis and [11C]raclopride for dopamine D2 receptor function on six genetically confirmed SCA6 patients, both with and without parkinsonism. To the best of our knowledge, this is the first dopamine receptor imaging study of patients with SCA6.ResultsMost patients had somewhat decreased dopaminergic function, and this decrease was significant in the caudate nucleus. In addition, one SCA6 patient with parkinsonism had whole striatal dysfunction of both dopamine synthesis and dopamine D2 receptor function.Conclusions The pathology of SCA6 may not be restricted to the cerebellum, but may also be distributed across various regions, including in both presynaptic and postsynaptic dopaminergic neurons to some degree. Patients with SCA6 may show apparent parkinsonism after the progression of neurodegeneration.

Kendo, a type of fencing using bamboo swords, is one of the most popular Japanese martial arts that is practiced by over four million people worldwide. ¹ Kendo players wear face masks that protect their heads, but only from front and side attacks (figure 1A). Repetitive head trauma in athletes engaged in contact sports has been associated with development of neurodegenerative disorders. ² Herein, we present the case of kendo player with a history of chronic headache, depression, and cognitive dysfunction, who developed occipital epilepsy followed by generalized tonic-clonic seizures, as a result of repetitive head injuries.

To investigate cerebral reactions to cognitive rehabilitation tasks, oxyhemoglobin changes were compared in 9 patients with cognitive impairments after traumatic brain injury (TBI) and 47 healthy controls using functional near infrared spectroscopy (fNIRS) during nine cognitive rehabilitation tasks employed at Nagoya City Rehabilitation Center. Forty-seven measurement channels were placed on the frontal to temporal cortices, and organized into seven channel regions. Oxyhemoglobin changes were normalized based on the mean oxyhemoglobin value at the resting state, and integrated throughout a task. Statistical analyses of the differences between the TBI patients and controls were performed with the two-sided Mann-Whitney U test. Oxyhemoglobin changes were high for both controls and TBI patients in the lateral frontal regions. Oxyhemoglobin changes in TBI patients tended to be higher than controls in the medial frontal regions for most training tasks, and significant differences (p < 0.05) were seen for two tasks in the medial frontal regions. Different regions were activated during the tasks in TBI patients compared to controls. fNIRS measurement is useful in the evaluation of changes of neuronal activities during rehabilitation tasks in TBI patients.

The aim of this study was to examine the sensibility of NIRS in observation of brain activation during a verbal fluency test. Twenty-three participants were given letter fluency and semantic fluency tests and the hemodynamism was measured by NIRS. Thirty-three pairs of optodes were attached, so they can measure signals from 52 channels consisting of adjacent pairs of emitters and detectors. Results were investigated in terms of the change of blood flow volume value of OxyHb for word generation. The results showed a significant interaction between task (letter fluency and semantic fluency) and cortical area (prefrontal and temporal) in the analysis of variance. Here, the prefrontal area showed marked activation in the left hemisphere during letter fluency task, whereas the temporal area showed activation in the semantic fluency task performance. These findings by NIRS confirmed different cerebral functions between semantic and letter fluency tasks, which were coincident with the findings by previous fMRI studies. Based on these findings, it is clear that NIRS is useful and provides sensitive new brain imaging techniques, which may provide a new horizon in the examination of human language perception and generation processes.

A system for evaluating dementia of the Alzheimer type (DAT) based on magnetic resonance (MR) imaging by means of fuzzy neural networks (FNNs) was investigated. The T1-weighted head MR transverse section images were obtained by a routinely performed examination. Nine slices including the thalamus were analyzed for each subject. Each MR image (MRI) was divided into four parts. The ratio of the brain area to the intracranial area was defined as the atrophy ratio. DAT severity was assessed by the Mini-Mental State (MMS) examination administered to each patient, and the results were used as teaching values for the FNN models. To construct the FNN model with high accuracy, MRI-based input variables were examined. Using atrophy ratios of 9 MRIs based on thalamically fiducial images and the corresponding areal or volumetric data as input variables, highly accurate FNN models were constructed that gave an average error of 1.29 points out of 30 in the MMS scores.