Hirotaka Kida

In vivo detection of cortical microinfarcts on ultrahigh-field MRI.

Cortical microinfarcts (CMIs) are detected as small foci restricted to the cerebral cortex in autopsy brains. CMIs are thought to be caused by cerebral amyloid angiopathy (CAA) in the elderly and may be a risk for dementia. We aimed to visualize CMIs, which remain invisible on conventional MRI, using double inversion recovery (DIR) and 3‐dimensional fluid attenuated inversion recovery (3D‐FLAIR) on 3‐Tesla MRI.

The effects of physical exercise with music on cognitive function of elderly people: Mihama-Kiho project.

Background Physical exercise has positive effects on cognitive function in elderly people. It is unknown, however, if combinations of non-pharmaceutical interventions can produce more benefits than single ones. This study aimed to identify if physical exercise combined with music improves cognitive function in normal elderly people more than exercise alone. Methods We enrolled 119 subjects (age 65–84 years old). Forty subjects performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM group), developed by YAMAHA Music Foundation; 40 subjects performed the same exercise without music (Ex group); 39 subjects were the control group (Cont group). Before and after the year-long intervention, each patient was assessed by neuropsychological batteries. MRIs were performed before and after intervention; the Voxel-based Specific Regional analysis system for Alzheimers Disease (VSRAD) was used to assess medial temporal lobe atrophy. Results Analysis of variance (ANOVA) was significant only in visuospatial function. The multiple comparison (ExM vs. Ex, ExM vs. Cont, Ex vs. Cont) was significant between the ExM and Cont group. Intra-group analyses before and after intervention revealed significant improvement in visuospatial function in the ExM group, and significant improvements in other batteries in all three groups. The VSRAD score significantly worsened in the ExM and Ex groups. Conclusions Physical exercise combined with music produced more positive effects on cognitive function in elderly people than exercise alone. We attributed this improvement to the multifaceted nature of combining physical exercise with music, which can act simultaneously as both cognitive and physical training. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000012148

Plasma protein profiling for potential biomarkers in the early diagnosis of Alzheimer’s disease

Abstract Objectives: Alzheimer’s disease (AD) is the most common cause of dementia in elderly persons. Since the pathology of AD develops slowly from a preclinical or early phase into a fully expressed clinical syndrome, at the time of diagnosis the disease has been progressing for many years. To facilitate the early diagnosis of AD, we performed protein profiling of blood in patients with mild AD as defined by the Functional Assessment Staging (FAST) scale. Methods: Plasma samples from mild AD patients and healthy controls were analyzed using two-dimensional differential gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF/MS) followed by peptide mass fingerprinting. Results: Three downregulated proteins were identified: apolipoprotein A-1, alpha-2-HS-glycoprotein, and afamin. Two proteins, including apolipoprotein A-4 and fibrinogen gamma chain, were upregulated in mild AD patients. Discussion: Our results suggest that altered expression levels of these proteins in plasma may yield candidate biomarkers for the early diagnosis of AD. Abbreviations: AD, Alzheimer’s disease; FAST, Functional Assessment Staging; 2D-DIGE, two-dimensional differential gel electrophoresis; MALDI-TOF/TOF/MS, matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry; CSF, cerebrospinal fluid; Aβ, amyloid beta; MMSE, Mini Mental State Examination; MRI, magnetic resonance imaging; NINCDS-ADRDA, National Institute for Neurological Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association; CHAPS, 3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate; DTT, dithiothreitol; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; DIA, differential in-gel analysis; BVA, biological variation analysis; CBB, Coomassie brilliant blue; 2DE, two-dimensional gel electrophoresis; TFA, trifluoroacetic acid; ACTH, adrenocorticotropic hormone; Apo A-1, apolipoprotein A-1; AHSG, alpha-2-HS-glycoprotein; Apo A-4, apolipoprotein A-4; MCI, mild cognitive impairment.

Mortality and life expectancy of Yokkaichi Asthma patients, Japan: Late effects of air pollution in 1960–70s

BackgroundThe incidence of chronic obstructive pulmonary disease (COPD) and bronchial asthma began increasing in early 1960s in the population of Yokkaichi-city (Mie Prefecture, Japan). The cause of the disease was sulfur oxide air pollution, and it is known as Yokkaichi Asthma. The pollution markedly decreased by the end of 1970s; no new cases have been reported since 1988. This study aimed at examining the late effects of air pollution on the health of Yokkaichi Asthma patients.MethodsMortality rate and life expectancy of patients, registered between 1965 and 1988, were investigated from 1975 through 2000.ResultsMortality rates for COPD and asthma in patients from Yokkaichi-city were significantly higher than in the whole population of Mie Prefecture. For all ages (except for males between 80 and 84 years in 1985), the life expectancy of both males and females were significantly reduced in patients from Yokkaichi-city as compared with the whole population of Mie Prefecture. The potential gains in life expectancy excluding the mortality for respiratory diseases including COPD and asthma were larger for all ages in patients from Yokkaichi-city.ConclusionMortality and life expectancy were adversely affected in patients from Yokkaichi-city, despite the fact that the air pollution problem has been already solved.

A longitudinal study of neuromelanin-sensitive magnetic resonance imaging in Parkinson's disease.

PURPOSE Neuromelanin-sensitive MR imaging (NMI) is an increasingly powerful tool for the diagnosis of Parkinsons disease (PD). This study was undertaken to evaluate longitudinal changes on NMI in PD patients. METHODS We examined longitudinal changes on NMI in 14 PD patients. The area and contrast ratio (CR) of the substantia nigra pars compacta (SNc) were comparatively analyzed. RESULTS The total area and CR of the SNc upon follow-up NMI were significantly smaller than those on initial NMI (from 33.5±18.9 pixels and 6.35±2.86% to 21.5±16.7 pixels and 4.19±2.11%; Wilcoxon signed-rank test, p<0.001 and p=0.022, respectively). The area and CR of the dominant side SNc upon initial NMI were significantly greater than those on follow-up NMI (from 15.3±9.1 pixels and 6.5±2.7% to 7.9±8.5 pixels and 3.7±2.9%; Wilcoxon signed-rank test, p=0.002 and p=0.007, respectively). On a case-by-case basis, the area of the SNc invariably decreased upon follow-up NMI in all patients. We further demonstrated that the total area and CR of the SNc negatively correlated with disease duration (Pearson correlation coefficient, r=-0.63, p<0.001 and r=-0.41, p=0.031, respectively). In area analyses, our results demonstrated very high intraclass correlation coefficients for both intra- and inter-rater reliability. CONCLUSION NMI is a useful and reliable tool for detecting neuropathological changes over time in PD patients.

Neuropsychological Features of Microbleeds and Cortical Microinfarct Detected by High Resolution Magnetic Resonance Imaging

BACKGROUND Lobar microbleeds (MBs) and cortical microinfarct (CMI) are caused by cerebral amyloid angiopathy in the elderly and increase in number in Alzheimers disease. OBJECTIVE The aim of this study is to elucidate the effects of lobar MBs and CMIs on cognitive function. METHODS The subjects were outpatients who visited the memory clinic of Mie University Hospital. Among 120 subjects, 109 patients fulfilled the inclusion criteria. We quantitatively estimated MBs and CMIs using double inversion recovery and 3D FLAIR images of 3T MRI. Neuropsychological assessments included intellectual, memory, constructional, and frontal lobe function. RESULTS Of the 109 patients, MBs and CMIs were observed in 68 (62%) and 17 (16%) subjects, respectively. Of the 68 patients with MBs, lobar MBs were found in 28, deep MBs in 8 and mixed MBs in 31. In each age group, the number of MBs increased in patients with CMI (CMI+ group) than those without CMI (CMI- group), and MBs and CMIs additively decreased MMSE scores. In psychological screens, the MBs+ group with more than 10 MBs showed significantly lower scores of category- and letter-WF than MB- group. The CMI+ group showed significantly worse scores than CMI- group in Japanese Ravens coloured progressive matrices, Trail Making Test-A, category- and letter-word fluency and copy and drawing of figures. CONCLUSION Lobar MBs and CMIs in the elderly frequently coexisted with each other and additively contributed to cognitive impairment, which is mainly predisposed to frontal lobe function.

The effectiveness of istradefylline for the treatment of gait deficits and sleepiness in patients with Parkinson’s disease

PURPOSE Istradefylline is useful in treating the wearing-off state in Parkinsons disease (PD). We investigated the effectiveness of istradefylline (ISD) in improving arousal, sleep, and gait deficits in patients with PD. METHODS We examined 14 patients with PD treated with ISD. We assessed the patients using the Unified Parkinsons Disease Rating Scale, Parkinsons Disease Questionnaire, Timed Up-and-Go test (TUG), Freezing of Gait Questionnaire (FOG-Q), Epworth Sleepiness Scale (ESS), and Parkinsons Disease Sleep Scale (PDSS) before and 1 month after ISD use. RESULTS ESS scores were significantly lower 1 month after the start of ISD treatment (6.79±6.50) than before the intervention (8.14±6.15, Wilcoxon signed-rank test, p=0.0033). PDSS scores were not significantly different 1 month after beginning the treatment (112±23mm) when compared to those before the intervention (110±27mm, Wilcoxon signed-rank test, p=0.40). TUG scores were not changed after 1 month of ISD use (14.9±8.3s) when compared to those before the intervention (21.3±30.0s, Wilcoxon signed-rank test, p=0.59). Although these measures were not significantly affected by ISD treatment, some patients remarkably improved after the treatment. FOG-Q scores were significantly lower 1 month after the beginning of treatment (9.79±7.16) than those before the intervention (12.14±5.82, Wilcoxon signed-rank test, p=0.030). CONCLUSIONS ISD may improve daytime sleepiness and FOG in patients with PD.

Physical Exercise with Music Reduces Gray and White Matter Loss in the Frontal Cortex of Elderly People: The Mihama-Kiho Scan Project

Findings from previous studies suggest that physical exercise combined with cognitive training produces more positive effects on cognitive function in elderly people than physical exercise alone. However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects. We hypothesized that the dual task group would experience greater benefits than the physical exercise alone and non-exercise control groups with regard to both cognitive function and brain plasticity. This study investigated the effect of physical exercise with musical accompaniment on structural brain changes in healthy elderly people. Fifty-one participants performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM), 61 participants performed the same exercise without music (Ex), and 32 participants made up the non-exercise group (Cont). After the 1-year intervention, visuospatial functioning of the ExM but not the Ex group was significantly better than that of the Cont group. Voxel-based morphometry analyses revealed that the ExM group showed greater right superior frontal gyrus volume and preserved volumes of the right anterior cingulate gyrus, left superior temporal gyrus, and insula. These results indicate that compared with exercise alone, physical exercise with music induces greater positive effects on cognitive function and leads to subtle neuroanatomical changes in the brains of elderly people. Therefore, physical exercise with music may be a beneficial intervention to delay age-related cognitive decline.

Improved Neural Processing Efficiency in a Chronic Aphasia Patient Following Melodic Intonation Therapy: A Neuropsychological and Functional MRI Study

Melodic intonation therapy (MIT) is a treatment program for the rehabilitation of aphasic patients with speech production disorders. We report a case of severe chronic non-fluent aphasia unresponsive to several years of conventional therapy that showed a marked improvement following intensive 9-day training on the Japanese version of MIT (MIT-J). The purpose of this study was to verify the efficacy of MIT-J by functional assessment and examine associated changes in neural processing by functional magnetic resonance imaging. MIT improved language output and auditory comprehension, and decreased the response time for picture naming. Following MIT-J, an area of the right hemisphere was less activated on correct naming trials than compared with before training but similarly activated on incorrect trials. These results suggest that the aphasic symptoms of our patient were improved by increased neural processing efficiency and a concomitant decrease in cognitive load.

Prediction of Cognitive Decline from White Matter Hyperintensity and Single-Photon Emission Computed Tomography in Alzheimer’s Disease

Background While several studies support an association of white matter hyperintensity (WMH) volume and regional cerebral blood flow (rCBF) with cognitive decline in Alzheimer’s disease (AD), no reports have simultaneously considered the effects of both factors on cognitive decline. Objective The purpose of the present study was to compare WMH volume and rCBF in relation to cognitive function by developing a new software program to fuse magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) data. Method We used MRI, SPECT, and neuropsychological data from 182 serial outpatients treated at the memory clinic of our hospital. Results Twenty-nine AD patients fulfilled the inclusion criteria (18 females, mean age: 73.1 ± 7.9 years, mean Mini-Mental State Examination: 23.1 ± 3.0). Analysis of variance revealed that posterior deep WMH (DWMH) volume was significantly larger than both anterior periventricular hyperintensity (PVH) and DWMH, and posterior PVH volumes. Multivariate regression analysis showed that increased volumes of the anterior PVH and the posterior DWMH and decreased rCBF of the parietal cortex negatively affected cognitive function. The other areas had no significant negative effects on cognitive function. Conclusion Our findings show that the volume of the posterior WMH was significantly larger than that of other areas, and the increased posterior WMH volume and decreased rCBF of the parietal cortex negatively affected cognitive function. Therefore, the posterior WMH volume and the parietal rCBF are key parameters of cognitive decline in AD patients.