Takafumi Miyachi

Incidence of dementia, Alzheimer disease, and vascular dementia in a Japanese population: Radiation Effects Research Foundation adult health study.

Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. Methods: 2,286 dementia-free subjects, aged ≧60 years, were followed for 5.9 years through biennial two-phase examinations. Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.

Disinhibition of the somatosensory cortex in cervical dystonia-decreased amplitudes of high-frequency oscillations.

OBJECTIVE To determine whether patients with cervical dystonia have electrophysiological signs of disinhibition in the somatosensory cortex by recording high-frequency oscillations (HFOs) in somatosensory evoked potentials (SEPs). METHODS HFOs were recorded in 13 patients and 10 age-matched control subjects, and the data were analyzed statistically by paired comparison and by Pearsons correlation. RESULTS In patients with cervical dystonia, the early part of HFOs showed a significant decrease in amplitude, and the amplitude ratios of both early and late parts of HFOs/N20 potential were also significantly decreased. The amplitudes of HFOs and N20 potential were linearly correlated in the control subjects but not in dystonia patients. CONCLUSIONS Patients with cervical dystonia may suffer from a disturbance of inhibition in the sensory cortex. This disturbance is reflected by decreased HFO amplitude, representing decreased activities of inhibitory interneurons in area 3b.

Structure and regulation of the human NeuroD (BETA2/BHF1) gene.

In this study, we isolated and characterized the human NeuroD (BETA2/BHF1) gene. This gene was found to consist of two exons and one intron. The promoter regions were well-conserved compared with the mouse NeuroD gene. Two transcription start points (TSPs) were determined by the oligo-capping method. One TATA box was located at -31 bp from the lower TSP. The results of a transient transfection assay using the human neuroblastoma cell line IMR-32 and hamster insulin tumor cell line HIT-T15 suggested that there are at least three positive regulatory regions in the promoter. In these regions, four E boxes (CANNTG), named the E1 to E4 boxes, and two GC boxes were present. Cotransfection of the NeuroD expression vector into IMR-32 cells enhanced the NeuroD promoter activity by about 4-fold. A deletion and mutation analysis revealed that the E1 and E4 boxes, especially the E1 box, are associated with autoactivation and that E2 and E3 boxes are not associated with autoactivation. As mutation analysis of E3 box showed a decrease in the enhancer activity to the basal level, it showed that the E3 box is important to activate the NeuroD transcription. These results raised the possibility that the NeuroD gene expression is positively regulated through the E box sequence, not only by NeuroD itself but also by another E box binding protein.

Magnetization Transfer Measurements of Brain Structures in Patients with Multiple System Atrophy

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.

Incidence and risks of dementia in Japanese women: Radiation Effects Research Foundation Adult Health Study.

BACKGROUND Although dementia has a great impact on public health, there are few reports on dementia incidence and risk factors for Asian populations. OBJECTIVES To determine incidence and risk factors of dementia, Alzheimer disease (AD), and vascular dementia (VaD) among Japanese women. METHODS Between 1992 and 1996, 1637 non-demented women aged > or =60 years were followed for an average of 5.9 years in RERFs Adult Health Study. Dementia diagnoses were made during biennial health examinations using a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for AD, and NINDS-AIREN for VaD. Potential risk factors were analyzed using Poisson regression analysis. RESULTS 161 cases of dementia (109 of AD and 56 of VaD, based on individual criteria) were newly diagnosed. Incidence increased dramatically with age, especially for AD. Probable AD decreased with increasing education level. Probable VaD was significantly associated with hypertension and stroke. Age at menopause did not show any effect on dementia. All dementia and probable AD were significantly associated with grip strength. CONCLUSIONS AD is predominant in dementia incidence among Japanese women. Modification of stroke risk factors and improvement of physical fitness may help prevent dementia.

Incidence of dementia among atomic-bomb survivors ― Radiation Effects Research Foundation Adult Health Study

Radiotherapy has been reported to cause neuropsychological dysfunction. Here we examined whether exposure to atomic bomb radiation affected the incidence of dementia among 2286 atomic bomb survivors and controls - all members of the Adult Health Study cohort. Study subjects were non-demented and aged >or=60 years at baseline examination and had been exposed in 1945 at >or=13 years of age to a relatively low dose (<or=4 Gy), compared with total dose from radiotherapy. Dementia diagnoses were made during biennial health examinations with a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for Alzheimer disease, and NINDS-AIREN for vascular disease. To estimate the effect of radiation on the dementia incidence rate, we applied Poisson regression analysis. Incidence per 1000 person-years was 16.3 in the <5 mGy group, 17.0 in the 5-499 mGy group, and 15.2 in the >or=500 mGy group. Alzheimer disease was the predominant type of dementia in each dose category. After adjustment for potential risk factors, radiation exposure did not affect the incidence rate of either all dementia or any of its subtypes. No case of dementia had a history of therapeutic cranial irradiation. Although we found no relationship between radiation exposure and the development of dementia among atomic bomb survivors exposed at >or=13 years old in this longitudinal study, effects on increased risk of early death among atomic bomb survivors will be considered.

A novel haplotype of spinocerebellar ataxia type 6 contributes to the highest prevalence in Western Japan

The highest prevalence rate of spinocerebellar ataxia type 6 (SCA6) in the worldwide population is in the Chugoku and Kansai areas of Western Japan, but the reason of this geographic characteristics is unclear. We investigated the predisposing haplotypes and their geographic distribution. Genotyping of five microsatellite markers and three single nucleotide polymorphisms linked to the CACNA1A gene in 150 Japanese SCA6 patients from unrelated 118 families revealed three major haplotypes, carrying a pool of one common haplotype core. A founder chromosome was thought to have historically diverged into at least three types. One of the major haplotypes newly identified showed a strong geographical cluster around the Seto Inland Sea in the Chugoku and Kansai areas of Western Japan, whereas the others were widely distributed throughout Japan. The distribution of predisposing haplotypes contributes to the geographical differences in prevalence of SCA6.

P4-113: Incidence of dementia among atomic bomb survivors: Radiation effects research foundation Adult Health Study

article i nfo Radiotherapy has been reported to cause neuropsychological dysfunction. Here we examined whether exposure toatomicbombradiationaffectedtheincidence ofdementiaamong2286atomicbomb survivorsand controls — all members of the Adult Health Study cohort. Study subjects were non-demented and aged ≥60 years at baseline examination and had been exposed in 1945 at ≥13 years of age to a relatively low dose (≤4 Gy), compared with total dose from radiotherapy. Dementia diagnoses were made during biennial health examinations with a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS- ADRDA for Alzheimer disease, and NINDS-AIREN for vascular disease. To estimate the effect of radiation on the dementia incidence rate, we applied Poisson regression analysis. Incidence per 1000 person-years was 16.3 in the b5 mGy group,17.0 in the 5-499 mGy group, and 15.2 in the ≥500 mGy group. Alzheimer disease was the predominant type of dementia in each dose category. After adjustment for potential risk factors, radiation exposuredidnotaffecttheincidencerateofeitheralldementiaoranyofitssubtypes.Nocaseofdementiahada history of therapeutic cranial irradiation. Although we found no relationship between radiation exposure and the development of dementia among atomic bomb survivors exposed at ≥13 years old in this longitudinal study, effects on increased risk of early death among atomic bomb survivors will be considered.

An elderly case of microscopic polyangiitis following bronchial asthma

A 78-year-old woman who had bronchial asthma for 15 years developed dysesthesia, neuralgia, muscle weakness and atrophy in both feet and her left hand. Prednisolone (maximum dose 80 mg) was not effective, and she displayed gait disturbance. Laboratory findings showed leukocytosis (neutrophils dominant), renal dysfunction, elevation of CRP and positive P-ANCA. Biopsy revealed vasculitis, and reduced density of myelinated fibers. Although steroid pulse therapy improved neuralgia and renal dysfunction, severe disability of motor function and sensory disturbance still remained. Vasculitis syndrome following bronchial asthma indicated Churg-Strauss syndrome (CSS), while severe renal dysfunction and lack of eosinophilia were symptoms compatible with microscopic polyangiitis (MPA). The present case showed properties of both MPA and CSS.

Characteristic features of folate‐deficient neurological diseases in the elderly

Background:  Folic acid (folate) deficiency causes neurological disorders in aged people, the characteristic features of which were examined.