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.

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.

Decay of silicon mounds: scaling laws and description with continuum step parameters

The decay of mounds about a dozen layers high on the Si(111)-(7x7) surface has been measured quantitatively by scanning tunneling microscopy and compared with analytic predictions for the power-law dependence on time predicted for a step-mediated decay mechanism. Conformably, we find an exponent 1/4 associated with the (3D) decay of the mound height and exponent 1/3 associated with the (2D) decay of top-layer islands. Using parameters from a continuum step model, we capture the essence of the kinetics. Qualitative features distinguish these mounds from multilayer islands found on metals.

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 using 11C-N-methyl-4-piperidyl benzilate (11C-NMPB) and positron emission tomography (PET). The subjects consisted of 37 (20 males and 17 females) healthy volunteers. The 11C-NMPB uptake was evaluated by the ratio method (regional 11C-NMPB uptake/Cerebellar 11C-NMPB uptake; rNMPB ratio). The correlation between sex, aging, and the 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.

Characterization of the Na+-ATPase gene (ZENA1) from the salt-tolerant yeast Zygosaccharomyces rouxii.

In order to clarify the relationship between the salt tolerance of Zygosaccharomyces rouxii and the function of Na+-ATPase, a gene which exhibited homology to the Na+-ATPase gene (ZENA1) of Saccharomyces cerevisiae was isolated from Z. rouxii. This newly isolated gene (ZENA1) encoded a product of 1048 amino acids. The predicted amino-acid sequence of Zena1p was highly homologous to that of S. cerevisiae Ena1p and Ena2p, and Schwanniomyces occidentalis Ena1p and Ena2p, but showed low homology to that of Zpma1p, which is the product of the Z. rouxii plasma membrane H+.ATPase gene (ZENA1). Zena1p shares the peptide motifs which have been suggested to participate in the function of ATPase. Expression of ZENA1 was observed, but was independent of NaCl shock. When ZENA1 was expressed in salt-sensitive S. cerevisiae under the regulation of a GAL1 promoter by using the expression vector pYES2, salt tolerance of the transformants was observed. The growth characteristics of Zena1Delta-disruptants of Z. rouxii and the pH profiles of their plasma membrane ATPase activity were almost the same as those of the wild-type strain, indicating that the function of Zena1p is of little relevance to the salt tolerance property of Z. rouxii. By considering the close relationship between the salt tolerance of Z. rouxii and the function of its Na+/H+-antiporter, we concluded that the extrusion of Na+ across the plasma membrane in Z. rouxii cells might be carried out mainly via the function of the Na+/H+-antiporter in a high salinity environment.

Cerebral muscarinic acetylcholinergic receptor measurement in Alzheimer's disease patients on 11C-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 of 11C-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 by 99mTc-HMPAO SPECT, and the CMRGlc was measured by 18FDG PET. The 11C-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 the 18FDG PET was the most sensitive method for detecting the degenerative regions in patients with AD.

Functional and structural brain imagings in dementia.

Dementia is a major psychiatric problem in elderly people. Recent developments in brain imaging have made practical contributions to the diagnosis of dementia, which is caused by spread of various kinds of lesions in the brain. It is important to make accurate diagnoses of dementia in living patients, in order to decide upon treatment and to predict life expectancy. Magnetic resonance imaging can reveal vascular lesions more sensitively than can X-ray computed tomography. Imaging methods of brain structures, however, can show only atrophies in dementing disorders caused by degeneration, like Alzheimer's disease. In contrast, functional imaging methods like single-photon emission tomography and positron emission tomography, measuring regional cerebral blood flow and/or metabolism, have capabilities to detect hypofunctional brain areas, before structural changes appear in the degenerative dementias. A specific finding for Alzheimer's disease in emission tomographic examinations is relative hypofunction of the posterior cerebral association cortices on both or one side in dementia without evidence of any cause for the dementia. This finding is expected to be positive evidence for the diagnosis of Alzheimer's disease.

Observation of the strain field near the Si(111) 7 x 7 surface with a new X-ray diffraction technique.

A new X-ray diffraction technique has been developed in order to measure the strain field near a solid surface under ultrahigh vacuum (UHV) conditions. The X-ray optics use an extremely asymmetric Bragg-case bulk reflection. The glancing angle of the X-rays can be set near the critical angle of total reflection by tuning the X-ray energy. Using this technique, rocking curves for Si surfaces with different surface structures, i.e. a native oxide surface, a slightly oxide surface and an Si(111) 7 x 7 surface, were measured. It was found that the widths of the rocking curves depend on the surface structures. This technique is efficient in distinguishing the strain field corresponding to each surface structure.

A study of verbal and spatial information processing using event-related potentials and positron emission tomography.

The activated cerebral regions and the timing of information processing in the hemispheres was investigated using event-related potentials (ERP) and regional cerebral blood flow (rCBF) as the neurophysiological indicators. Seven men and one woman (age 19-27 years) were asked to categorize two-syllable Japanese nouns (verbal condition) and to judge the difference between pairs of rectangles (spatial condition), both tests presented on a monochrome display. In the electroencephalogram (EEG) session, EEG were recorded from 16 electrode sites, with linked earlobe electrodes as reference. In the positron emission tomography (PET) session, rCBF were measured by the 15O-labeled H2O bolus injection method. Regions of interest were the frontal, temporal, parietal, occipital and central lobes, and the entire cerebral hemispheres. When the subtracted voltages of the ERP in homologous scalp sites were compared for the verbal and spatial conditions, the significant differences were at F7.F8 and T5.T6 (the 10-20 system). The latencies of the differences at T5.T6 were around 200, 250 and 320 ms. A significant difference in rCBF between the verbal and spatial conditions was found only in the temporal region. It was concluded that early processing of information, that is, registration and simple recognition, may be performed mainly in the left temporal lobe for verbal information and in the right for spatial information.

Negative correlation of P50 peak latencies and reaction times in a simple reaction task.

We investigated the influence of stimulus characteristics and tasks (count and simple reaction tasks) on auditory P50. Ten normal volunteers served as subjects. EEGs and auditory evoked potentials were obtained from Fz, Cz, Pz, C3, C4, T3 and T4 referred to linked earlobes (LE) and balanced non-cephalic (BN) electrodes. In the recordings using a BN reference there were significant negative correlations between the reaction times and P50 peak latencies at Fz, Cz, Pz, C3 and C4. In the LE reference recordings there were negative correlations but these did not reach statistical significance. The results are discussed with reference to the activation of the LE reference and the neural sources of P50. The findings suggest the possibility that reaction times are determined at the very early stage of auditory information processing.

[The relationship between the cerebral blood flow, oxygen consumption and glucose metabolism in primary degenerative dementia].

The CBF, CMRO2 and CMRGlu were measured in patients with primary degenerative dementia including 5 patients with dementia of Alzheimer's type and 4 patients with Pick's disease, and then the correlation between the cerebral blood flow and energy metabolism was evaluated. The control subjects consisted of 5 age-matched normal volunteers. The CBF, CMRO2 and CMRGlu decreased in the bilateral frontal, temporal and parietal regions in the patients with Alzheimer's dementia, while they decreased in the bilateral frontal and temporal regions in the patients with Pick's disease. Both the CBF and CMRO2 were closely correlated with each other. However, the CMRGlu was more severely impaired than the CBF or CMRO2 in both pathological conditions. These results suggested that CMRGlu began to decrease before the reduction of the aerobic metabolism and thus measuring the CMRGlu is considered to be the most sensitive method for detecting abnormal regions in primary degenerative dementia.

[A longitudinal study of CMRGlu in dementia of Alzheimer type].

We studied the serial changes of CMRGlu in 6 patients with dementia of Alzheimer type. All patients demonstrated moderately severe dementia at the initial PET scan. Serial PET scans were performed at an interval of 12 to 24 months. Five of the 6 patients showed a deterioration of clinical symptoms at the second scan. The global CMRGlu serially decreased in all patients. An asymmetry of CMRGlu in both the frontal and parietal regions was observed at the initial PET scan, while the direction of asymmetry was preserved at the second PET scan. The ratios (frontal/parietal and parietal/striatum) of CMRGlu showed no interval change. Therefore, CMRGlu was considered to decrease progressively throughout the entire brain in patients with moderately severe dementia of Alzheimer type.

HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern.

Positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) and single-photon emission tomography (SPET) of 99mTc-hexamethylpropylene amine oxime (HMPAO) were performed under identical resting conditions within 3 h in 20 patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 13 normal persons. In the temporoparietal association cortex similar impairment of relative regional cerebral glucose metabolism (rCMRGl) and relative HMPAO uptake (rCBF) was found. In addition PET showed hypometabolism in the occipital association cortex. The functional pattern was condensed to a ratio of regional values of association areas divided by regional values of structures that are typically less affected by AD. In normals this ratio was significantly related to age for PET metabolic data (r = -0.66, P = 0.01). The ratio was significantly lower in AD than in VD and controls for both rCMRGl and rCBF. In AD only, the metabolic ratio was related to severity of dementia (r = 0.54, P = 0.003) and age (r = 0.64, P = 0.003). Metabolic differences between normals and AD patients were less obvious in old age. In contrast, there were no significant correlations between the perfusion ratio and severity of dementia or age. Comparing the metabolic and perfusion ratio by receiver operating characteristic curves, PET differentiated AD from normals only marginally better than SPET. Differentiation between AD and VD was much better achieved by PET. Our results suggest that both PET and SPET can distinguish AD patients from controls, whereas for differentiation between AD and VD SPET is of little value.

Difference of regional cerebral metabolic pattern between presenile and senile dementia of the Alzheimer type: a factor analytic study.

Positron emission tomographic studies using metabolic ratios to represent the contrast between certain brain regions have shown differences of cerebral glucose metabolism between presenile and senile dementia of Alzheimer type (DAT). In this study, factors for regional variance of cerebral metabolism in 61 patients with probable Alzheimer's disease were obtained using principal component analysis (PCA). The difference between two age groups of DAT patients according to age at onset < or = 65 years (n = 30) and > 65 years (n = 31) were investigated. A PCA using nine pairs of cerebral regions normalized to cerebellum for reduction of intersubject variability identified five regional factors for cerebral metabolism: one each for the left and right temporo-parietal cortex, and the other three for frontal cortex, primary visual and sensorimotor cortex, and mesial temporal sensorimotor cortex, and mesial temporal cortex. The age groups differed significantly only in the factor for the right temporo-parietal cortex, with a more prominent metabolic reduction in presenile than senile DAT. Severity of dementia was correlated with the factors for the right and left temporo-parietal cortex. The effect of age at onset on glucose metabolism of the right temporo-parietal cortex was independent from that of dementia severity in DAT.

[Multi-functional dementia rating scale: reliability and clinical validity].

A new rating method was designed to evaluate five symptoms of dementia; disorders of memory, cognition, language, visuospatial functions, and personality, which are defined as recent neuropsychological criteria for dementias by Cummings and Benson. Thirty-two items were made from the items of the Hasegawa dementia scale and neuropsychological tests. Scales for the five symptoms of dementia were then constituted of the items. In semi-structured interview, 113 demented patients and 16 normal elderly volunteers were rated. Interrater reliability of the five symptom scales were tested by ANOVA ICC and all the symptoms had a significant reliability. The scores of the five symptoms were correlated with each other and with the scores of the Hasegawa dementia scale. A Principal Component Analysis was applied to the scores of the five symptoms. The largest principal component had correlations with the scores of the Hasegawa dementia scale and the scores of the all five symptoms and was interpreted as a factor for severity of dementia. This component explains about 70% of total variance of the data. The other 30% of the variance were explained by four principal components which were interpreted as factors of the differences of the scores of the symptom scales. Relations between the scores of the symptoms and regional cerebral blood flow (rCBF) measured using SPECT were investigated in 25 moderately demented patients which met the criteria of probable Alzheimer's disease of NINCDS-ADRDA. rCBF was calculated as a ratio of 123I-IMP uptake of the areas to the mean uptake of right and left cerebellum. Significant correlations were found between the scores of memory symptom and the rCBF of the left temporal lobe (r = 0.59: p < 0.01) and between the scores of personality changes and the rCBF of the both frontal lobes (r = 0.58, 0.54: p < 0.01). Results suggest the possibility that the distribution of brain damage reflects symptoms in dementia and also supports the validity of analytic evaluation of dementia symptoms by this scale.

[Stimulus time dependence of cerebral blood flow response to photic stimulation].

The time dependency of rCBF response to photic stimulation in the primary visual cortices was studied using H215O bolus-injection and PET. The subjects consisted of 5 normal volunteers aged from 25 to 40 years old. Their regional CBF was measured at 2 min and 7 min after the start of photic stimulation (frequency, 10 Hz). The percentage increases of rCBF were 19.6 +/- 7.9% (mean +/- SD, range: 8.9-27.6%) in the primary visual cortex on the left side and 23.2 +/- 13.6% (2.5-35.8%) on the right side at 2 min, respectively, while, in comparison, they were 25.3 +/- 20.0% (1.8-49.7%) on the left side and 25.3 +/- 16.4% (3.5-44.5%) on the right side at 7 min, respectively. No significant difference was found in the rCBF responses between at 2 min and 7 min. Therefore, the taming effect does not need to be considered when carrying out a photic stimulation study.