Decreased stimulus-driven connectivity of the primary visual cortex during visual motion stimulation in amnestic mild cognitive impairment: An fMRI study.

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.

Radiation Effects on Cognitive Function Among Atomic Bomb Survivors Exposed at or After Adolescence.

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.

Trajectories of cognitive function in dementia-free subjects: Radiation Effects Research Foundation Adult Health Study.

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.

Relevance of in vivo neurophysiological biomarkers for mild cognitive impairment and Alzheimer's disease.

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.

Understanding the Pathophysiology of Alzheimer's Disease and Mild Cognitive Impairment: A Mini Review on fMRI and ERP Studies.

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.

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=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.

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 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.

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 > 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.

[Examination of frontal lobe function of Parkinson disease patients using Stroop reaction time].

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.

Difference in somatosensory evoked fields elicited by mechanical and electrical stimulations: Elucidation of the human homunculus by a noninvasive method.

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.

Activation of human SII cortex during exploratory finger movement and hand clenching tasks.

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.

Quantitative assessment of cerebral blood flow in genetically confirmed spinocerebellar ataxia type 6.

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.

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 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.

Frequency of asymptomatic microbleeds on T2*-weighted MR images of patients with recurrent stroke: association with combination of stroke subtypes and leukoaraiosis.

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.

Human reactions to physical stimulus and the removal of such stimulus as recorded by magnetoencephalography.

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.

Detection of cervical nerve root hypertrophy by ultrasonography in chronic inflammatory demyelinating polyradiculoneuropathy.

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.

[Somatosensory evoked potentials/fields--exploration of brain function].

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.

Effects of dementia on mortality in the radiation effects research foundation adult health study.

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.