Atsushi Ichimiya

High b value diffusion-weighted imaging is more sensitive to white matter degeneration in Alzheimer's disease

It has been reported that diffusion-weighted imaging (DWI) can detect white matter degeneration in the Alzheimers disease (AD) brain. We hypothesized that imaging of the slow diffusion component using high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI, and therefore we studied the effects of high b value on lesion-to-normal contrast and contrast-to-noise ratio (CNR). Seven AD patients and seven age-matched normal subjects were studied with full-tensor DWI at three different b values (1000, 2000, and 4000 s/mm(2)) without changing echo time or diffusion time, and the mean diffusivities in the parietal and occipital regions were measured. Statistical analyses revealed that use of higher b values significantly improves both lesion-to-normal contrast and CNR. We concluded that high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI.

Decreased serum brain-derived neurotrophic factor in trained men

The purpose of this study was to clarify the effect of physical activity on the level of serum brain-derived neurotrophic factor (BDNF). The serum BDNF level in trained men who have participated in regular sport activity (n=12) was compared to that in sedentary subjects (n=14). The physical activity levels expressed as total energy expenditure, move-related energy expenditure and walking count in the trained were significantly higher than those in the sedentary. The serum BDNF level in the trained men was found to be lower than that in the sedentary (19.54+/-4.53 ng/ml vs. 23.63+/-2.94 ng/ml, respectively, P<0.01). The serum BDNF level showed a significant negative correlation with daily total energy expenditure (r=-0.507, P<0.05), movement-related energy expenditure (r=-0.503, P<0.05), and walking count (r=-0.480, P<0.05). These results may suggest that vigorous habitual physical activity decrease the serum BDNF level.

Quantitative MRI findings and cognitive impairment among community dwelling elderly subjects

Objectives: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. Methods: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. Results: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123–2.208), cerebral atrophy (OR 0.761, 95%CI 0.587–0.987), and lower education (OR 0.682, 95%CI 0.544–0.855) for subjects with a cognitive impairment. Conclusions: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia.

Cerebrovascular responsiveness to hypercapnia in Alzheimer's dementia and vascular dementia of the Binswanger type.

Alzheimers dementia is thought to be a primary degenerative dementia, whereas vascular dementia of the Binswanger type is an entity of vascular dementia. We evaluated the cerebrovascular responsiveness to hypercapnia to clarify the differences in the cerebral hemodynamics between two groups of patients. The subjects were eight younger control subjects, five age-matched control subjects, five Alzheimers patients, and five patients with vascular dementia of the Binswanger type. Summary of Report In the resting state, the regional cerebral blood flow was low in both Alzheimers dementia and vascular dementia of the Binswanger type. The responsiveness to hypercapnia was preserved in Alzheimers dementia, whereas it was impaired in vascular dementia of the Binswanger type in the cerebral cortices and in the deep white matter. Conclusions These results suggest that small vascular lesions exist in vascular dementia of the Binswanger type but not in Alzheimers dementia, even though regional cerebral blood flow was thought to decrease by hypometabolism in both types of dementia.

Positron emission tomographic (PET) studies in dementia.

Positron emission tomographic (PET) studies of regional cerebral glucose metabolism were performed in patients with various types of dementia, patients with Parkinsons disease but without dementia, and healthy normal controls. Patients with Alzheimer-type dementia showed significant decreases in glucose metabolism in frontal, temporal, parietal, sensory-motor and striatal regions. Patients with Picks disease revealed decreased glucose metabolism in frontal and temporal regions. Parkinsonian patients with dementia had significant reductions of glucose metabolism in frontal, temporal, parietal, occipital, sensory-motor and striatal regions. Patients with Huntingtons disease revealed decreased glucose metabolism in frontal, parietal and striatal regions. Patients with Creutzfeldt-Jakobs disease showed marked decreases in glucose metabolism throughout all brain regions. On the other hand, patients with Parkinsons disease but without dementia exhibited no reductions of cerebral glucose metabolism. Cerebral glucose hypometabolism in these various types of dementia might reflect neuronal dysfunction and cell death.

Posterior cingulate hypoperfusion in Alzheimer's disease, senile dementia of Alzheimer type, and other dementias evaluated by three-dimensional stereotactic surface projections using Tc-99m HMPAO SPECT

Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimers disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.

Cerebral muscarinic acetylcholinergic receptor measurement in Alzheimer’s disease patients on11C-N-methyl-4-piperidyl benzilate — Comparison with cerebral blood flow and cerebral glucose metabolism—

We studied the cerebral muscarinic acetylcholinergic receptor (mACh-R) by means of11C-N- methyl-4-piperidyl benzilate (11C-NMPB) and positron emission tomography (PET) in Alzheimer’s disease (AD) cases, and the findings were compared with the cerebral blood flow (CBF) and the glucose metabolism (CMRGlc) to evaluate the relationship between the mACh-R and the CBF or the CMRGlc. The subjects consisted of 18 patients with AD and 18 age and sex matched normal volunteers. The patients were clinically diagnosed according to the criteria of the NINDS-ADRDA as having “probable AD” and were thus classified into two groups (mild and moderate AD) according to the severity of dementia determined by DSM-III-R. The CBF was measured by99mTc-HMPAO SPECT, and the CMRGlc was measured by18FDG PET. The11C-NMPB uptake was evaluated by the graphical method and the ratio method (ROIs/Cerebellum). A significant mACh-R decrease and more severe CMRGlc decrease in the cortical region was seen in mild and moderate AD. The decrease in the CBF was not as obvious as that in the mACh-R and the CMRGlc.Our study thus suggested that the mACh-R decreased in patients with AD, and that the18FDG PET was the most sensitive method for detecting the degenerative regions in patients with AD.

Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy.

Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometabolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP.

Relationship between Both IQ and Mini-Mental State Examination and the Regional Cerebral Glucose Metabolism in Clinically Diagnosed Alzheimer’s Disease: A PET Study

In order to clarify the hypofunction in which brain areas demonstrate a decline in Intelligence Quotient (IQ), we examined correlations between the IQ and Mini-Mental State Examination (MMSE) and regional cerebral metabolic rate of glucose (rCMRglc) measured using positron emission tomography (PET) in 26 patients with clinically diagnosed Alzheimer’s disease (AD). The MMSE scores and full-scale IQ (FSIQ) showed significant correlations with the rCMRglc in the temporal and parietal lobes on both sides and in the left frontal lobe, which were significantly reduced in comparison to those in the normal controls. A multiple regression analysis showed only the MMSE score to predict verbal IQ (VIQ), performance IQ (PIQ) and FSIQ. VIQ was also predicted by the rCMRglc in the left parietal lobe, while PIQ was predicted by the age at onset. The results suggested MMSE to be an index of dementia severity reflected by general intelligence as shown by IQ in AD, and a reduction in the VIQ can thus be used as an index of the left parietal dysfunction, which is not expressed by MMSE.

Sex-related differences in the muscarinic acetylcholinergic receptor in the healthy human brain —A positron emission tomography study—

We evaluated the sex-related differences in the decline of the cerebral muscarinic acetylcholinergic receptor (mACh-R) due to aging by using11C-N-methyl-4-piperidyl benzilate (11C-NMPB) and positron emission tomography (PET). The subjects consisted of 37 (20 males and 17 females) healthy volunteers. The11C-NMPB uptake was evaluated by the ratio method (regional11C-NMPB uptake/Cerebellar11C-NMPB uptake was evaluated by the ratio method (regional11C-NMPB rNMPB ratio in normal aging was evaluated by a multiple regression analysis. The rNMPB ratio was higher in females than in males throughout the entire cerebral region (p<0.01-p<0.0001) and the rNMPB ratio might thus possibly decline with age more rapidly in females. Our study therefore revealed the existence of sex-related differences in the cerebral mACh-R.