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Motion perceptual deficits are common in Alzheimer's disease (AD). Although the posterior parietal cortex is thought to play a critical role in these deficits, it is currently unclear whether the primary visual cortex (V1) contributes to these deficits in AD. To elucidate this issue, we investigated the net activity or connectivity within V1 in 17 amnestic mild cognitive impairment (aMCI) patients, 17 AD patients and 17 normal controls (NC) using functional magnetic resonance imaging (fMRI). fMRI was recorded under two conditions: visual motion stimulation and resting-state. The net activity or connectivity within V1 extracted by independent component analysis (ICA) was significantly increased during visual motion stimuli compared with that of the resting-state condition in NC, but not in aMCI or AD patients. These findings suggest the alteration of the net activity or connectivity within V1, which may contribute to the previously reported motion perceptual deficits in aMCI and AD. Therefore, the decreased net V1 activity measured as the strength of the ICA component may provide a new disease biomarker for early detection of AD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The first asymmetric total synthesis of andranginine (1) via an asymmetric Morita-Baylis-Hillman reaction and a diastereoselective intramolecular Diels-Alder reaction has revealed that natural andranginine (1) isolated from Kopsia arborea existed as a scalemic mixture and contained predominantly the (16R,21S) form rather than the (16S,21R) form.

Background: The objective of this study was to investigate radiation effects on longitudinal pre-dementia cognitive decline among participants who developed dementia as well as on those who did not develop dementia during follow-up., Methods: Measuring cognitive function with the Cognitive Abilities Screening Instrument approximately every 2 years, we followed 1844 atomic bomb survivors participating in the Adult Health Study of the Radiation Effects Research Foundation from 1992 to 2011. Participants were adolescents or older when exposed to between 0 and 4 Gy. Approximately 15% and 40% of participants were exposed to ≥1 Gy and <5 mGy, respectively. At study start, participants were dementia-free and between 60 and 80 years old. Three-quarters of the participants returned after baseline, averaging 8.4 years of follow-up. During follow-up, 313 developed dementia. We used cognitive scores before dementia onset for analysis and a mixed-effects model to estimate radiation effects on longitudinal change of cognition, adjusting for dementia occurrence, age, sex, and education., Results: Cognition level was significantly associated with age, education, and dementia occurrence but not with radiation dose or sex. Cognitive decline accelerated with increasing age, especially among participants who developed dementia. Neither radiation nor education was significantly associated with the degree of deterioration with age. Radiation did not modify the different cognitive decline by dementia occurrence., Conclusions: Radiation did not significantly affect cognition among atomic bomb survivors exposed at or after adolescence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To investigate associations between age, sex, education, and birth cohort and global cognitive decline among a population that would most likely not progress to dementia., Methods: A total of 1538 dementia-free subjects aged 60 to 80years in 1992 were followed up through 2011 without dementia occurrence. We assessed cognitive function using the Cognitive Ability Screening Instrument (CASI). Using stepwise-like model selection procedure, we built mixed-effects models for initial cognition and longitudinal cognition., Results: Initial CASI scores for younger age and more years of formal education were higher than those for older and less education. Sex did not show a significant effect. In the longitudinal analysis, cognitive decline became more rapid with increasing age. Sex and education did not modify the degree of deterioration with age. CASI scores were higher for younger cohorts and men due to differences in education levels., Conclusion: Among dementia-free subjects, age is an important predictor of cognitive function level and cognitive decline. Education level affects cognitive function level, but did not affect cognitive decline. The results have implications not only for elucidation of the aging process, but also for reference in dementia screening., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Visuospatial dysfunction including defects in motion perception in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients.

The prevalence of Alzheimer's disease (AD) is predicted to increase rapidly in the coming decade, highlighting the importance of early detection and intervention in patients with AD and mild cognitive impairment (MCI). Recently, remarkable advances have been made in the application of neuroimaging techniques in investigations of AD and MCI. Among the various neuroimaging techniques, functional magnetic resonance imaging (fMRI) has many potential advantages, noninvasively detecting alterations in brain function that may be present very early in the course of AD and MCI. In this paper, we first review task-related and resting-state fMRI studies on AD and MCI. We then present our recent fMRI studies with additional event-related potential (ERP) experiments during a motion perception task in MCI. Our results indicate that fMRI, especially when combined with ERP recording, can be useful for detecting spatiotemporal functional changes in AD and MCI patients.

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 RERF's 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.

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=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.

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 > or =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., ((c) 2008 S. Karger AG, Basel)

The purpose of this study is to examine frontal lobe function of non-dementia Parkinson's disease (PD) patients. We examined the neuropsychological and behavioral evaluation (Stroop reaction time: SRT). Target image (20%) and non-target image (80%) were presented to PD patients, healthy elderly controls, and healthy young subjects at random. We instructed subjects that the button should pressed on the target image. This study was designed to investigate the mental set under three conditions. The Stroop test, Word Fluency Test (WFT), and Geriatric Depression Scale (GDS) were used to assess cognitive function. The SRT of PD were congruent condition and incongruent condition increased compared with simple condition. The delay of a similar SRT was seen in the healthy elderly control and young groups. However, the SRT of PD patients was slower under incongruent condition than under congruent condition. It appears that PD spent time on judgment in under incongruent condition because the meaning of the character did not correspond to the color of the character. Because, there were no significant between PD and healthy elderly subjects in Stroop test, WFT, and GDS, frontal lobe function had a partial deficit. The SRT of PD was increased by the partial deficit in information processing ability in addition to movement dysfunction.

Purpose: The aim of this study was to evaluate the biomechanical stability of various internal fixation systems for subcondylar fractures., Materials and Methods: Eighteen identical synthetic mandibles were used. Left condylar processes were cut to mimic perpendicular subcondylar fracture and right sides were mimicked oblique subcondylar fracture. The fixation systems used included single 4-hole mini adaptation plate, double fixation with the same plates, single 4-hole mini dynamic compression plate (DCP), Eckelt lag screw system, Wurzburg lag screw plate system and double 4-hole biodegradable miniplates made of poly L-lactide (PLLA). In oblique fractures, one of the screws fixing plates was used bicortically through bone fragments. The loading vector simulated physiologic forces to the condyle on biting with servohydraulic testing machine until failure was reached. Load-displacement curve, maximum load for failure, and stiffness were measured., Results: In perpendicular fracture, double adaptation plate showed the highest level of tolerance load followed by Eckelt lag and double PLLA plate. In stiffness, double adaptation plate and Eckelt lag screw showed higher level of stiffness, whereas double PLLA was almost at the same level of single DCP. In oblique fracture, double adaptation plate showed the highest strength., Conclusions: In this laboratory setting, double adaptation plates fixation proved to have superior biomechanical stability in both fracture conditions. Eckelt lag screw showed good stability in the perpendicular fracture, however, it was weak in the oblique fracture.

Background and Purpose: Previous studies have shown microbleeds to be a risk factor for intracerebral hemorrhage and white matter hyperintensity (WMH) to be a risk factor for ischemic stroke. This study was performed to determine whether combinations of the presence or absence of microbleeds and advanced WMH are risk factors for subsequent recurrent stroke types., Methods: In 266 patients with stroke, microbleeds on T2*-weighted MR images were counted, and WMH on T2-weighted images was graded. Patients were divided into 4 groups by the combinations of the presence or absence of microbleeds and advanced WMH and were followed up for stroke recurrence., Results: During a mean follow-up period of 564.8 +/- 220.5 days, 26 patients developed recurrent strokes, including 10 intracerebral hemorrhages and 16 ischemic strokes. Patients with microbleeds without advanced WMH (n = 42) developed only intracerebral hemorrhages (n = 8), and the recurrence rate of intracerebral hemorrhage in those patients estimated by the Kaplan-Meier method was the highest in the 4 groups (14.3% in 1 year and 21.2% in 2 years). In contrast, patients with advanced WMH without microbleeds (n = 39) developed only ischemic strokes (n = 6), and the estimated recurrent rate of ischemic stroke in those patients was the highest in the 4 groups (10.5% in 1 year and 17.4% in 2 years). Cox proportional hazards regression analysis revealed that microbleeds were associated with intracerebral hemorrhage (hazard ratio [HR], 85.626; 95% confidence interval [CI], 6.344-1155.649) and that advanced WMH was negatively associated with intracerebral hemorrhage (HR, 0.016; 95% CI, 0.001-0.258). Advanced WMH was associated with ischemic stroke (HR, 10.659; 95% CI, 2.601-43.678)., Conclusion: It appears that patients at high risk of subsequent intracerebral hemorrhage or ischemic stroke can be identified by combinations of the presence or absence of microbleeds and advanced WMH.

Both leukoaraiosis and asymptomatic microbleeds are associated with small-artery diseases. Although an association between hyperhomocysteinemia and leukoaraiosis has been reported, no studies have evaluated the association between total homocysteine (tHcy) level and presence of microbleeds in stroke patients. We evaluated the association between tHcy level and leukoaraiosis or microbleeds in stroke patients. In 102 patients with stroke (69.5 +/- 10.3 years old, 54 men and 48 women), microbleeds on T2*-weighted MR images were counted, leukoaraiosis on T2-weighted images was graded and fasting plasma tHcy concentrations were measured. Plasma tHcy level was significantly higher in patients with advanced leukoaraiosis than in those without advanced leukoaraiosis (13.9 +/- 4.6 micromol/l vs. 10.2 +/- 3.4 micromol/l, P < 0.0001). Plasma tHcy level was not significantly different in patients with microbleeds and those without microbleeds (11.3 +/- 4.1 micromol/l vs. 11.4 +/- 4.3 micromol/l, P = 0.9441). Elevated tHcy level is significantly and independently associated with advanced leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130-1.565] but not with the presence of microbleeds. Elevated tHcy level appears to be associated with ischemic small-artery disease rather than with bleeding-prone small-artery disease.

We recently recorded somatosensory evoked fields (SEFs) elicited by compressing the glabrous skin of the finger and decompressing it by using a photosensor trigger. In that study, the equivalent current dipoles (ECDs) for these evoked fields appeared to be physiologically similar to the ECDs of P30m in median nerve stimulation. We sought to determine the relations of evoked fields elicited by mechanically stimulating the glabrous skin of the great toe and those of electrically produced P40m. We studied SEFs elicited by mechanical and electrical stimulations from the median and tibial nerves. The orientations of dipoles from the mechanical stimulations were from anterior-to-posterior, similar to the orientations of dipoles for P30m. The direction of the dipole around the peak of N20m from median nerve electrical stimulation was opposite to these directions. The orientations of dipoles around the peak of P40m by tibial nerve stimulation were transverse, whereas those by the compression and decompression stimulation of the toe were directed from anterior-to-posterior. The concordance of the orientations in ECDs for evoked fields elicited by mechanical and electrical stimulations suggests that the ECDs of P40m are physiologically similar to those of P30m but not to those of N20m. The discrepancy in orientations in ECDs for evoked field elicited by these stimulations in the lower extremity suggests that electrical and compression stimulations elicit evoked fields responding to fast surface rubbing stimuli and/or stimuli to the muscle and joint., ((c) 2005 Wiley-Liss, Inc.)

We used electric median nerve stimuli to elucidate the functional properties of neurons in the human secondary somatosensory cortex during exploration of small objects and muscle contraction. Somatosensory evoked fields were recorded from nine healthy subjects with a 204-channel neuromagnetometer. Electrical stimuli were applied once every 3 s to the left median nerve at the wrist. The conditions during the stimulation were rest (control session), exploration of small objects (exploration session) and clenching the hand while the wrist was being electrically stimulated (clench session). The strengths of equivalent current dipoles of evoked fields from the secondary somatosensory cortex were increased during the exploration session, but those of evoked fields were decreased by the clench session.

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 Pearson's 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.

Background: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide expansion. The characteristics of regional cerebral blood flow (rCBF) in SCA6 patients have not been established, whereas it has been reported that decreased rCBF in the cerebrum seems to be a remote effect of cerebellar impairment in other cerebellar disorders., Objective: To clarify the characteristics of rCBF, including cerebro-cerebellar relationship, and its correlation with clinical manifestations in patients with genetically confirmed SCA6 using quantitative assessment of rCBF by brain single-photon emission computed tomography (SPECT)., Design: Technetium Tc 99m ethyl cysteinate dimer SPECT study using a Patlak plot. Patients Hiroshima University Hospital, Hiroshima, Japan. Ten patients with SCA6 and 9 healthy controls. Main Outcome Measure The rCBF of the cerebellar vermis, cerebellar hemisphere, and frontal lobes., Results: In SCA6 patients, rCBF was decreased only in the cerebellar vermis and hemisphere compared with healthy controls, and this was inversely correlated with duration of illness. The rCBF in the frontal lobes was slightly correlated with duration of illness without statistical significance. The rCBF in the vermis was inversely correlated with severity of dysarthria, but there was no significant correlation with CAG repeated expansions., Conclusions: Decrease in rCBF was found only in the cerebellum and was associated with duration of illness, dysarthria and ataxia, and cerebellar atrophy. No remote effect of cerebellar hypoperfusion was found in the SCA6 patients.

We studied the cortical evoked fields elicited by the examiner's touch on glabrous skin of the subject's index finger. Two main components of evoked fields were elicited, and these dipoles were located in the primary somatosensory cortex contralateral to the side of the subject's index finger touched by the examiner. When the timing of removal of the examiner's finger triggered the data acquisition using the photosensor, the strength of the dipole from early evoked fields was stronger than that from late ones. We showed that these evoked fields were elicited by removal and touch of the examiner's finger respectively in response to the mechanical compression and decompression of the skin.

Background and Purpose: Asymptomatic microbleeds shown by T2*-weighted MR imaging are associated with small-artery diseases, especially with intracerebral hemorrhage. Few studies have focused on the prevalence of microbleeds in patients with recurrent stroke. We investigated frequency of microbleeds in patients with recurrent stroke and association of presence of microbleeds with a combination of stroke subtypes and severity of leukoaraiosis., Methods: The study population consisted of 102 patients with primary stroke and 54 patients with recurrent stroke. Microbleeds were counted and classified by using T2*-weighted MR imaging with a 1.0-T system., Results: Patients with recurrent stroke showed a significantly higher prevalence of microbleeds (68.5%) than did patients with primary stroke (28.4%) (P <.0001). Among patients with recurrent stroke, the highest frequency of microbleeds occurred in those with intracerebral hemorrhage alone (92.3%), with the next highest frequency occurring in those with a combination of intracerebral hemorrhage and ischemic stroke (76.5%) and then those with ischemic stroke alone (50.0%) (P <.05). Leukoaraiosis was more severe in patients with recurrent stroke than in patients with primary stroke, and correlations between grade of microbleeds and severity of leukoaraiosis were found in patients with primary stroke (r = 0.367, P <.001) and in patients with recurrent stroke (r = 0.553, P <.0001). Logistic regression analysis identified recurrent stroke (odds ratio, 4.487; 95% confidence interval, 1.989-10.120) and leukoaraiosis (odds ratio, 5.079; 95% confidence interval, 2.125-12.143) as being significantly and independently associated with microbleeds., Conclusion: Asymptomatic microbleeds are observed to occur frequently in patients with recurrent stroke, either hemorrhagic or ischemic stroke, and are closely associated with the severity of leukoaraiosis.

Several studies have demonstrated abnormal MRI findings in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), especially hypertrophy and abnormal enhancement of spinal nerve roots, but there have been few reports on ultrasonographic findings of spinal nerve roots in CIDP. To determine whether ultrasonography (US) enables detection of hypertrophy of the cervical nerve roots, how frequently hypertrophy occurs in CIDP, and whether US findings correlate with any clinical and laboratory features, US of cervical nerve roots was performed using a 7.5-MHz linear-array transducer in 13 CIDP patients and 35 control subjects. A coronal oblique plane with a transducer placed on the lateral side of the neck was used to visualize the cervical nerve roots just after their point of exit from the cervical foramina, and their diameters were measured. US demonstrated hypertrophy of the cervical nerve roots in 9 (69%) of the 13 CIDP patients as compared with findings in control subjects. The degree of hypertrophy was significantly associated with the level of CSF protein (chi2=5.8, p<0.05, logistic simple regression analysis) but not with other clinical features. US is considered to be a useful method for evaluating cervical nerve root hypertrophy, which is frequently seen in patients with CIDP, particularly in patients with elevated level of CSF protein.

Background: Although dementia is rarely listed on death certificates, it does contribute to mortality. The predominant immediate causes of death coincident with dementia are pneumonia and cardiovascular diseases., Objective: To estimate the impact of dementia on specific mortality risks., Methods: We applied DSM-III/R criteria for Alzheimer's disease (AD) and vascular dementia (VaD) to 2,172 subjects of the Adult Health Study of the Radiation Effects Research Foundation who were 60 or more years old when examined from 1992 to 1996. The underlying causes of death were compiled from death certificates. We performed a Poisson regression analysis to evaluate specific causes of mortality for which AD or VaD was a significant risk factor., Results: The relative risk of mortality was 2.2 for AD and 2.4 for VaD. Mortality from pneumonia and stroke was elevated for both types of dementia, independent of other medical conditions. AD was also associated with death from trauma., Conclusion: Dementia was a predictor of death due to pneumonia, stroke, and trauma among the Japanese elderly. The prevention and early detection of those conditions are important in the medical care and treatment of dementia cases., (Copyright 2004 S. Karger AG, Basel)

We have summarized the history of electroencephalography(EEG) since 1875, when a paper by Richard Caton was published describing the first EEG recordings in animals. Somatosensory evoked potentials (SEPs) were recorded by George Dawson in 1951. Thereafter, SEPs were developed for clinical use with other evoked potentials such as auditory evoked potentials(VEPs). To understand evoked potentials, related mechanism of induction of far-fields-potentials(FFP) following stimulation of the median nerve has been discussed. SEPs consisted of P9, N9, N10, P11, N11, N13, P13, P14, N18, N20 and P20/P22. Scalp recorded P9 FFP arises from the distal portion of the branchial plexus as reflected by N9 stationary negative potential recorded over the stimulated arm. Cervical N11 and N13 arise from the root entry zone and dorsal horn, respectively. Scalp recorded P13, P14 and N18 FFP originate from the brainstem. In this communication, magnetoencephalography(MEG) and results of one of our recent studies on somatosensory evoked fields(SEFs) are also discussed. One of the important features of MEG is that magnetic signals detected outside the head arise mainly from cortical currents tangential to the skull. Since the net postsynaptic current follows the orientation of cortical pyramidal cells, the MEG signals mainly reflect activity of the fissural cortex, whereas radial current may remain undetected. In our study, we demonstrated SEFs elicited by compression and decompression of a subject's glabrous skin by a human operator. Their dipoles were tangentially oriented from the frontal lobe to parietal lobe.

Objectives: To investigate the association between midlife risk factors and the development of vascular dementia (VaD) or Alzheimer's disease (AD) 25 to 30 years later., Design: A prevalence study within a longitudinal cohort study., Setting: Subjects in the Adult Health Study (a prospective cohort study begun in 1958) have been followed through biennial medical examinations in Hiroshima, Japan., Participants: One thousand seven hundred seventy-four subjects in Hiroshima, Japan born before September 1932 (1,660 with no dementia, 114 with dementia (51 with AD, and 38 with VaD) diagnosed from 1992 to 1997 according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria)., Measurements: The subjects were examined for effect on dementia of sex, age, education, atomic bomb radiation dose, and midlife factors associated with risk (smoking, alcohol intake, physical activity, dietary habits, systolic blood pressure (SBP), body mass index, and history of diabetes mellitus) that had been evaluated in 1965-1970., Results: VaD prevalence increased significantly with age, higher SBP, and lower milk intake. The odds ratios of VaD for age (in 5-year increments), SBP (10 mmHg increments), and milk intake (almost daily/less than four times a week) were 1.29, 1.33, and 0.35, respectively. The risk factors for VaD were compatible with the risk factors for stroke in this study population. AD prevalence increased significantly with age and lower education. Other midlife factors and radiation dose did not show any significant association with VaD or AD., Conclusion: Increased SBP and low milk intake in midlife were associated with VaD detected 25 to 30 years later. Early behavioral control of the risk factors for vascular disease might reduce the risk of dementia.

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.

Somatosensory evoked fields were recorded to determine the effects of movement and attention on high-frequency oscillations during active finger movements of the ipsilateral and contralateral sides in response to electrical stimulation of the median nerve. A whole-scalp neuromagnetometer was used to record somatosensory evoked fields from eight subjects following electric median nerve stimulation at the wrist. The following three sessions were performed: (1). rest, (2). movement of fingers on the ipsilateral in response to stimulation and (3). movement of fingers on the contralateral in response to stimulation. The somatosensory evoked fields with a wide-bandpass (0.1-1000 Hz) were recorded. High-frequency oscillations and N20m were separated by subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. The maximum amplitude of high-frequency oscillations decreased during finger movements accompanying a decrease in somatosensory N20m dipole strength. Activation of the motor cortex appeared to suppress both the amplitude of high-frequency oscillations and the N20m dipole strength.

Although neuropsychological dysfunction is found among A-bomb survivors exposed in utero as it is among patients who receive central nervous system radiotherapy, neuropsychological examinations have not been conducted on the survivors. Its prevalence may be increased as a result of the increased rate of strokes reported among those exposed to a high radiation dose. In this study, we examined the effects of radiation exposure on cognitive function among adult survivors in the Adult Health Study (AHS). The study subjects were men and women born prior to September 1932 who had undergone biennial examinations during the period 1992-1996 in Hiroshima or 1993-1998 in Nagasaki. We evaluated cognitive performance for 3,113 subjects with the Cognitive Abilities Screening Instrument (CASI), and we examined the relationship between cognitive performance and potentially related factors (sex, age, city where the subjects were exposed, years of education, and radiation dose). In contrast to exposure to radiotherapy, exposure to atomic bomb radiation had no apparent effect on cognitive function. Factors that did affect cognitive function were age, sex, city and years of education. Further investigation, including examination of other neurological functions, is required before a final conclusion regarding radiation-induced neurological dysfunction can be reached.

Background: Prospective studies have shown that cognitive impairment is a strong and consistent risk factor of physical disability. However, cognitive impairment has been based on the result of a single screening tool., Objective: To investigate the role of cognition in the subsequent incidence and decline of functional disability in basic activities of daily living (ADL) and instrumental activities of daily living (IADL) after a full assessment of dementia., Methods: A group of 1,358 Japanese atomic bomb survivors aged 61 years or older who lived in the community or in institutions in Hiroshima City were followed for 4 years. During the baseline survey (1993-1995), subjects were administered a screening test for cognitive impairment. Those suspected of dementia underwent a series of cognitive tests (Hasegawa's dementia scale, Clinical Dementia Rating) and a neurological examination. The diagnosis of dementia was made according to DSM-III-R criteria. Study subjects were questioned about their reported ADL and their IADL. During the follow-up period, deaths were recorded and a follow-up survey (1997-1999) used to assess ADL and IADL performance., Results: Dementia, even after adjustment for age, sex and history of stroke, was a strong predictor of functional disability, as indicated by ADL (odds ratio, OR = 14.0; confidence interval, CI = 5.4-36.3), IADL (OR = 10.1, CI = 2.2-46.4), and also by assessment of decline in ADL (OR = 9.8, CI = 4.2-22.8) or IADL status (OR = 3.9, CI = 1.8-8.3)., Conclusion: Dementia is an important determinant of functional status. Deterioration in ADL is more significant than deterioration in IADL, suggesting that factors other than cognition, such as motivation or perceptual, sensory and motor abilities, may be important in IADL performance. This study confirms previous findings on risk factors that affect functional ability and extends our knowledge by examining several criteria of function that are important in the daily lives of elderly people., (Copyright 2002 S. Karger AG, Basel)

A 68-year-old woman was admitted with dysesthesia on both soles, hands and buttocks. She first noticed the dysesthesia in the left first toe two years before admission. One year before admission, serum creatine kinase and lactate dehydrogenase levels were elevated but she had no clinical symptoms suggesting myopathy. Nerve conduction study showed no apparent abnormalities, and an electromyogram showed mild myogenic change. Computed tomography of the muscle showed fatty degeneration of the trunk, major gluteus muscle, and biceps femoris muscle and atrophic change of the biceps femoris muscle. Muscle biopsy revealed a slight variation in fiber size, the presence of cytochrome c oxidase (CCO)-negative fibers by CCO staining, ragged-red fibers by Gomori trichrome staining, and mild denervation fiber by neuron specific enolase (NSE) staining. Analysis of her mitochondrial DNA (mtDNA) revealed a large deletion of mtDNA (approximately 8.5 Kb), and mitochondrial neuromyophy was diagnosed. The frequency of mtDNA deletion increases with aging. Although her mtDNA abnormality was compatible with chronic progressive external ophthalmoplegia (CPEO), we speculate that the aging process may be contributed to the mtDNA abnormality, which would be related to the late onset of her symptoms. As the phenotype of this mitochondrial disorder shows a wide variation and mtDNA abnormality is more frequent among elderly people, we should consider the possibility of mitochondrial disorders even in elderly people.

We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation.

To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patient's age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.

When stimulating the mixed nerve to record evoked potential, both sensory and motor fibers are activated before entering the spinal cord. The N10 potential has been described as an antidromic motor evoked potential based on results obtained by recording at the anterior midneck. In the present study, we examined the changes in latencies of Erb's potential, N10, and N13 by stimulating the median nerve distally at the wrist and proximally at the elbow. The conduction velocity of N10 calculated by the difference between N10 latencies at the two stimulation points was consistent with motor conduction velocity, although N13 conduction velocity estimated by the same method reflected a sensory conduction velocity. A positive relation was also observed between the indirect latency from the stimulation point to the anterior root as calculated using the equation (F - M - 1) / 2 (ms) and the direct latency to the negative peak of the N10 potential. Our data support the notion that N10 represents antidromic motor potential originating in the spinal entry zone of the anterior root.

Objective: To assess MRI signal abnormalities of the superior cerebellar peduncle (SCP) in progressive supranuclear palsy (PSP) patients., Material and Methods: Signal changes were examined on proton density-weighted images (PDWI) and on T2-weighted images (T2WI) of SCP in 9 PSP patients, and findings were compared to those in 20 Parkinson's disease patients and 20 age-matched control subjects., Results: We observed effacement or lack of clarity of the low signal on PDWI in SCP in 4 of 9 PSP patients, but not in any of the Parkinson's disease patients or control subjects. These signal changes were not observed on T2WI., Conclusions: The signal changes on PDWI may be a specific finding reflecting demyelination and gliosis of SCP in PSP. Our findings suggest that evaluation of SCP on PDWI may be helpful in the diagnosis of PSP patients.

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.

We measured the apparent diffusion coefficient (ADC), using diffusion-weighted imaging (DWI) and signal intensity on T2-weighted MRI in the cerebral white matter of patients with progressive supranuclear palsy (PSP) and age-matched normal subjects. In PSP, ADC in the prefrontal and precentral white matter was significantly higher than in controls. There was no significant difference in signal intensity on T2-weighted images. The ADC did correlate with signal intensity. The distribution of the elevation of ADC may be the consequence of underlying pathological changes, such as neurofibrillary tangles or glial fibrillary tangles in the cortex. Our findings suggest that ADC measurement might be useful for demonstrating subtle neuropathological changes.

Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS.

We describe a 16-year-old female patient affected by photo-induced temporal lobe epilepsy. During intermittent photic stimulation she showed a photoparoxysmal response in the EEG. This case was diagnosed from clinical symptoms, single photon emission computer tomography, and EEG data. The clinical symptoms were relieved by the administration of carbamazepine. As these photoparoxysmal responses were observed not only during photic stimulation, but also when patient was closing her eyes during an eye-opening test in complete darkness, we propose the existence of an alternative pathway such as from the extraocular muscles or orbicularis oculi, or activation of cortical activity due to the change of consciousness by closing eyes in inducing photosensitive epilepsy. We describe an additional case and discuss a novel aspect of photo-induced temporal lobe epilepsy., (Copyright 2000 BEA Trading Ltd.)

The Cognitive Abilities Screening Instrument (CASI) was developed by Japanese and American researchers, including the authors, to examine cognitive functions, based on previous neuropsychological tests, such as Hasegawa's Dementia Scale and the MMSE. From the Adult Health Study (AHS) population of the Radiation Effects Research Foundation, 2052 men and women aged 60 or over and living in Hiroshima were evaluated for their cognitive functions using the CASI. Dementia was diagnosed in 93 and 1,959 were considered not to suffer from dementia based on the DSM-III-R criteria using neurological examination and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) completed by caregivers. Multivariate regression analysis not only indicated that total score was higher with lower age and higher education but that the slope of its decrease is steeper with higher age and fewer years of education. The slope of score decrease with increase of age was steeper for women than for men. Furthermore, CASI items were categorized by domains of cognitive function. Multivariate regression analysis for each cognitive domain showed clear effects of age and level of education. The effect of age for the nondementia subjects was large in cognitive domains dealing with temporal orientation, short-term memory, and list-generating fluency. The most useful cognitive domains for diagnosing dementia were temporal orientation, short-term memory, and list-generating fluency, as was indicated by high sensitivity and specificity.

We reported an autopsy case of cerebral infarction with primary lung cancer. The patient was a 50-year-old man. Despite having been treated with warfarin potassium and ticlopidine hydrochloride, he relapsed cerebral infarction. His laboratory data on admission showed that lupus anticoagulant was positive, together with a high value of beta-thromboglobulin, thrombin-antithrombin III complex, markers of platelet and coagulation activation, CEA and CA 19-9. The autopsy finding revealed a primary papillary adenocarcinoma in the right lower lung, multiple cerebral infarction, renal infarction, pulmonary infarction and splenic infarction. The atherosclerotic changes were mild in the whole tissues and findings of vasculitis were not observed. Recurrence of cerebral infarction was effectively suppressed with the addition of steroid therapy to antithrombotic therapy. This case was considered as catastrophic antiphospholipid syndrome. It is necessary to differentiate antiphospholipid syndrome in case of the abnormal coagulation and fibrinolytic factors with recurrent cerebral infarction. Moreover, systemic examinations are important, because malignant tumor may exist on the background of the case.

The resistance against oral antibiotics to Streptococcus pneumoniae (S. pneumoniae) isolated from adult patients with respiratory tract infections in the Kurume area in 1998 was studied. The frequency of resistant strains, which were isolated penicillin-intermediate S. pneumoniae and resistant S. pneumoniae (PISP, PRSP) were both 41.2%. We examined the minimal inhibitory concentrations (MIC) of oral antibiotics and the susceptibility ratio of the strains for the drugs based on the breakpoint MIC. The breakpoint MIC of pneumonia against oral beta-lactam antibiotics to PISP, PRSP, which were determined by Japan Society of Chemotherapy, were high in the order of FRPM > CDTR, CFPN > CFTM > CFDN, CPDX. In the case of the new oral quinolones, DU6859a > SPFX > LVFX > CPFX showed good results, in this order, DU6859a showed the most significant inhibitory effect to PISP, PRSP (MIC90 0.06 microgram/ml). By serotyping the percentage of 19, 6, 23 was 42.9%, 21.4% and 14.3%.

A 77-year-old man was admitted because of muscle weakness in both upper and lower extremities. Diabetes mellitus was diagnosed in 1988 and he had been treated by oral hypoglycemic agents. He had a common cold at the end of January, 1997. Muscle weakness appeared in the upper extremities, followed by the lower extremities at the end of February. No sensory disturbance or dysuria was recognized. Nerve conduction study revealed distally dominant demyelinating polyneuropathy. Guillain-Barré's syndrome was diagnosed and he recovered completely following immunological absorption therapy (IAT). However, he had quadriplegia again at the end of April. He was treated by IAT combined with corticosteroid and has shown no relapse. In June, 1997, gastric cancer was detected by upper gastrointestinal fiberscopy and subtotal gastrectomy was performed. Judging from this clinical course, this case seems to be chronic inflammatory demyelinating polyneuropathy (CIDP) with acute onset. Many kinds of causes often contribute to the pathogenesis of neuropathy in the elderly. So in cases of progression or worsening, we should consider such possibilities and it is necessary not to exclude treatable causes of neuropathy.

Background: We investigated the effect of age on nerve conduction parameters with special reference to the compound muscle action potential (CMAP) duration and duration ratio., Method: We examined 295 subjects (aged 15-85 years old) with no previous history or present signs of peripheral neuropathy. The subjects were divided into 3 groups: young (15-34 years old); intermediate (35-64 years old), and old (65-85 years old)., Results: CMAP amplitude was lower in the old group than in the young group; however, the CMAP ratio (proximal CMAP/distal CMAP) did not change with age. The CMAP duration and duration ratio did not differ among the 3 groups. The CMAP area was smaller in the old group, but the area ratio was almost constant among the 3 groups., Conclusion: We suggest that age-related changes in CMAP amplitude, duration or area may occur uniformly, at least in the forearm and the calf segment, in routine nerve conduction studies. The present findings also provide useful and reliable information, regardless of age, in diagnosing peripheral neuropathy.

A 75-year-old man had noticed muscle atrophy and weakness of his right hand and forearm at the age of 25. The symptoms slowly progressed and then stopped. Right hand tremor appeared at about age 40. There was no symptom in his left upper extremity, and his gait was normal. He now shows severe muscle atrophy in his right hand and forearm. There was distally dominant weakness of the right upper extremity and his hand grip was 0 kg on the right and 25 kg on the left. On admission there was no weakness in the bilateral lower extremities. He had postural tremor in both hands and fingers. The tendon reflexes were hypoactive in the upper extremities and normal in the lower extremities. Abnormalities in the superficial sensation were unremarkable, whereas vibration sensation in both the upper and lower extremities was mildly disturbed. Electromyography revealed chronic denervation, especially in the right upper extremity. The sensory nerve conduction study results and somatosensory evoked potentials in the upper extremities were normal. Cervical MRI demonstrated spondylotic changes, canal stenosis from the C5 to C7 levels, and compression of the spinal cord. His hand tremor was dominant on the right with a peak frequency of about 7 Hz. Tremor frequency and power were decreased by mechanical load. Hirayama's disease (juvenile muscular atrophy of unilateral upper extremity) was the most probable diagnosis, although aging might have produced various additional abnormalities. The tremor seen in this patient showed characteristics of enhanced physiological tremor.

Objectives: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia., Design: A prevalence study within a longitudinal cohort study., Setting: The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations., Participants: Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions., Measurements: In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly., Results: The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure., Conclusion: This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.

Objective: To clarify the characteristic magnetic resonance imaging (MRI) findings in patients with spinocerebellar ataxia 6 (SCA6) diagnosed by genetic analysis., Patients and Methods: Using MRI, we examined 10 patients genetically diagnosed as having SCA6 and 40 control subjects., Results: The mean (+/-SD) CAG repeat length in 10 patients with SCA6 was 22.9 +/- 1.3. There was a significant inverse correlation between the CAG repeat size and age at onset in the SCA6 group (r = -0.86, P = .003). In patients with SCA6, the areas of the cerebellar vermis and hemispheres in sagittal MRI were significantly smaller than those in the control subjects. In transaxial MRI, the anteroposterior diameter of the pons and the diameter of the middle cerebellar peduncle were mildly decreased and the red nucleus was slightly atrophied in patients with SCA6. There was no significant difference in the diameter of the midbrain, medulla oblongata, fourth ventricle, superior cerebellar peduncles, dentate nucleus, or globus pallidus between the SCA6 and control groups. A high-signal intensity in the transverse pontine fibers was not observed in any of the patients with SCA6 on T2-weighted and/or proton-weighted axial MRI., Conclusions: The cerebellum and its afferent and efferent systems were affected in patients with SCA6. These results seem to distinguish the MRI findings of SCA6 from those of other forms of spinocerebellar ataxia.

Background: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan., Method: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises., Results: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia., Conclusions: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.