Prevalence of dementia in the rural village of Hanazono-mura, Japan.

We studied the prevalence of dementing disorders in a rural municipality of Japan (Hanazono-mura), using a door-to-door two-phase design. In phase 1, the Hasegawa's Dementia Scale-Revised was applied as a screening test to all subjects aged 65 years and older (n = 201). Among subjects screened positive, 17 were diagnosed with dementia in phase 2. The prevalence (cases/100 aged 65 years and older) was 8.5 for all types of dementia, 3.5 for Alzheimer's disease, 3.0 for vascular dementia, and 2.0 for other dementia (including mixed dementia). The prevalence of dementia was slightly but consistently higher in men than women at all ages. The overall prevalence was higher in women for Alzheimer's disease and in men for vascular dementia.

Involvement of Onuf's nucleus in amyotrophic lateral sclerosis.

The Onufrowicz (Onuf's) nuclei from eight amyotrophic lateral sclerosis (ALS) cases and nine neurological control cases were studied histologically and morphometrically. To clarify the factors relating to the involvement of the Onuf's nucleus in ALS, we correlated the relationships among the age at death, clinical duration, morphometric findings for Onuf's neurons, and neuronal numbers in the posteroposterolateral (PPL) nuclei in the ALS cases with those in neurological controls. Intracytoplasmic inclusions such as Bunina bodies, ubiquitin-reactive inclusions, and conglomerate inclusion were found in the Onuf's neurons in ALS, but not in the controls. The total number of Onuf's neurons in the ALS cases was not decreased, but that of normal-appearing neurons was decreased while that of atrophic neurons was increased. Significantly decreased perikaryal, nuclear and nucleolar areas and decreased perikaryal (P)/nuclear and P/nucleolar area ratios of Onuf's neurons were found in ALS, not only in the atrophic neurons but also in the normal-appearing neurons, compared with the controls. The shrinkage in Onuf's neurons of ALS was different from that seen in the ageing process or in the axonal reactions of controls with atonic bladder. In ALS, the morphometric findings for the Onuf's neurons showed no correlation with age at death, clinical duration, or number of PPL neurons. Our results indicate that in ALS Onuf's nucleus is principally vulnerable to the ALS process, although the degree of degeneration differs from that seen in other motor neurons. The involvement of Onuf's nucleus might be slowed due to factors specific to this nucleus, including the biochemical and autonomic properties of the nucleus; nevertheless, it is histologically classified as part of the somatic cell column.

[Alzheimer's disease and trace elements].

The etiology of Alzheimer's disease (AD) still remains unknown in spite of intensive research efforts. Recent genetic linkage studies have been reported regarding some candidate genes for familial Alzheimer's disease, such as amyloid precursor protein (APP) gene and apolipoprotein E gene. On the other hand, several risk factors of AD have been revealed by epidemiological studies, including age, family history, head trauma, thyroid dysfunctions and aluminum (Al). Our study of bulk sample analysis in AD brain using neutron activation analysis showed a significant increase of Al and iron (Fe) concentrations, especially in the cerebral cortices compared with age-matched controls. Based on these results, the possible role of trace elements on the etiopathogenesis of AD is discussed.

Age-related changes in occipital alpha rhythm of adults with Down syndrome.

A power spectral analysis was performed on occipital EEGs recorded from 36 Down Syndrome (DS) subjects aged 15 to 54 and compared with two control groups; 47 healthy volunteers (Control) and 42 mentally retarded people without DS (MR). The frequencies of occipital alpha rhythms of DS showed a significant inverse correlation with chronological age, while Control and MR did not. The average frequencies of DS were significantly low even in the youngest age-group in comparison with those of Control, and also decreased in the age-groups of 35 and older compared with MR. It was considered that a slowing of alpha rhythm was a manifestation of premature aging that occurred in the underdeveloped brains of DS.

[Visuo-postural control of schizophrenics--variations of sway area during horizontal eye movement].

In the present study, we investigated the neurological mechanism of commonly known specific or unnatural postures in schizophrenic patients. Using a gravimeter, body sway studied in 26 chronic schizophrenic patients, 10 schizoaffective disorder patients and 21 normal subjects. During eye fixation at a target while keeping an upright posture, schizophrenic patients presented a larger gravimetric area than the normal subjects and the patients with schizoaffective disorder. There was a negative correlation (r = -0.509) between the standard deviation of the sway gravimetric area during fixation and the dose of neuroleptics in schizophrenic patients, but no correlation was found in patients with schizoaffective disorder (r = -0.01), although they took neuroleptics in a similar regimen to that for the schizophrenics. There was no correlation between the standard deviation of the sway gravimetric area during fixation and the duration of illness. There was also no correlation between the former and the amplitude ratio of saccades during smooth pursuit eye movements. When horizontal eye movements pursuing the target were loaded in this experiment, both the normal subjects and the patients with schizoaffective disorder showed a decrease in a loaded gravimetric area and a tendency towards postural stabilization. However, schizophrenic patients having higher SANS scores (Andreasen) presented an increase in gravimetric area. This suggests that schizophrenic patients with higher SANS score may have organic cerebellar changes related to impairment of the mechanism of visual and postural coordinations.

The association between Alzheimer's disease and thyroid disease in Rochester, Minnesota.

To determine whether an association exists between Alzheimer's disease (AD) and thyroid disease, we carried out two studies in the population of Rochester, Minnesota. We reviewed medical records of a cohort of 198 women with histologically confirmed Hashimoto's thyroiditis (1935 to 1974) for evidence of subsequent dementia, applying the criteria used for dementia in a previous determination of incidence and prevalence rates in this population. From a total of 4,197 person-years of follow-up, eight cases of AD were diagnosed, whereas the expected number was 5.8. The standardized morbidity ratio was 1.37, which failed to reach statistical significance. The second study was a retrospective case-control comparison that sought any relationship between AD and all thyroid disorders, using a previously identified (1960 to 1979) AD cohort (N = 646) and their age- and sex-matched controls. For myxedema there was a positive association for AD without significance, whereas in Graves' disease there was a significant negative association for AD.

Involvement of Onuf's nucleus in ALS. Demonstration of intraneuronal conglomerate inclusions and Bunina bodies.

Onuf's nucleus of 3 ALS cases was examined histologically, morphometrically and for metal content. Case 1 showed conglomerate inclusions (CIs), cases 2 and 3 showed Bunina bodies in Onuf's nucleus. Electron microscopy showed that CIs were intracytoplasmic accumulations of 10 nm neurofilaments with discrete borders. Onuf's neurons in ALS showed a significant decrease (P less than 0.001) in the cytoplasmic, nuclear and nucleolar areas in comparison with neurons of age-matched controls and elderly controls. Metal analysis of the sacral spinal cords by alpha particle-excited X-ray fluorescence analysis (PIXE) showed relatively high Al levels in the ALS cases compared with controls. Morin staining revealed intense green fluorescence (indicating Al) in the nucleoli and cytoplasm of the CI-containing neurons, but not in the CIs themselves. The appearance of CIs or Bunina bodies and neuronal atrophy in Onuf's nucleus seems to indicate that this structure is also involved in the disease process of ALS, although it is less vulnerable than most other motor ganglia.

[The inhibitory effect of elastase on calcium increase in brain and spinal cord of rabbits with atherosclerosis induced by cholesterol-rich diet].

The aim of present experiment was to investigate the decalcified effects of exogenous elastase in liver, kidney and central nervous system (CNS) of rabbits with atherosclerosis experimentally induced by the modified procedure of Kritchevsky et al. Twenty five male rabbits, weighing approximately 2 kg, were divided into 6 groups. Animals were fed for 3 months with standard diet (group A), standard diet containing 1.5% cholesterol (group B) and 1.5% cholesterol-rich diet plus intraperitoneal (ip) daily administration of elastase 450 EL. U/kg (group C). Another groups were kept for 6 months with standard diet (group D), standard diet containing 0.67% cholesterol (group E) and 0.67% cholesterol-rich diet plus same dose of elastase (group F). The rabbits treated with cholesterol-rich diet were confirmed to be induced atherosclerosis biochemically as well as histologically. All groups were maintained under these conditions for experimental periods and allowed tap water. After 3 and 6 months, blood collected by cardiocentesis using ether anesthesia and then sacrificed to remove CNS and internal organs. Blood had stood for 1 hour at room temperature. Serum was separated by centrifugation at 3,000 rpm for 10 min to determine total cholesterol, triglyceride, phospholipids, HDL-cholesterol, and so on. Calcium contents in the cerebral frontal lobe, cerebellum, pons, spinal cord, liver and kidney were measured by neutron activation analysis method. In this experiment the amelioration of atherosclerosis by ip administration of elastase was ascertained. In rabbits given cholesterol-rich diet, calcium content in CNS tissues was higher than that of another tissues and paralleled to a rise of serum cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reactor neutron activation analysis for aluminium in the presence of phosphorus and silicon. Contributions of 28Al activities from 31P(n, alpha) 28Al and 28Si(n, p) 28Al reactions].

Reactor neutron activation analysis for aluminium in samples containing phosphorus and silicon was studied. The experiments were performed by using neumatic tube of the Kyoto University Reactor (KUR). At first, the ratios of the 28Al activity produced from 27Al(n, gamma) 28Al reaction by thermal neutrons to that from 31P(n, alpha) 28Al reaction by fast neutrons, and to that from 28Si(n, p) 28Al reaction were measured by gamma-ray spectrometry. With a ratio of about 5 for the thermal to fast neutron flux of KUR, the ratio of the 28Al activity from aluminium to that from phosphorus was to be 812 +/- 7, and to that from silicon 282 +/- 3. Secondly, the contributions of 28Al activities from phosphorus and silicon and the determination limit of aluminium were calculated for various parameters, such as fast neutron flux, thermal to fast neutron flux ratio, amounts of phosphorus and silicon, etc. Thirdly, on the basis of these results, aluminium contents in spinal cords and brains of amyotrophic lateral sclerosis, Parkinsonism-dementia complex and control cases were determined.

[Determination of the Ca/P atomic ratio in the spinal cord of patients with amyotrophic lateral sclerosis by neutron activation and X-ray fluorescence analysis].

Ca/P atomic ratios in spinal cords of seven amyotrophic lateral sclerosis (ALS) cases were determined by neutron activation and X-ray fluorescence analyses, and were compared with those of seven control cases. In order to obtain calibration curves, the standard samples with 0.01-0.1 of Ca/P atomic ratio were prepared by mixing diammonium hydrogen phosphate with calcium carbonate. In neutron activation analysis, gamma-ray spectra of 49Ca and beta-ray intensities of 32P produced from (n, gamma) reactions of the spinal cords and standard samples were measured by Ge(Li) and GM detectors, respectively. In X-ray fluorescence analysis, the samples were excited with 1.6 MeV alpha particle beam accelerated by a Van de Graaff accelerator, manganese K X-rays from 55Fe radioactive source and rhodium K alpha X-rays from X-ray tube, respectively. The characteristic X-ray spectra were measured by Si(Li) or proportional detector. From the peak areas on the spectra and beta-ray intensities, the Ca/P atomic ratios in spinal cords were determined. Based on these results, the Ca/P atomic ratio of precipitate including calcium and phosphorus in spinal cord of ALS case was calculated. As a result, the Ca/P atomic ratios in spinal cords of ALS and control cases were 0.018-0.021 and 0.030-0.049, respectively. The calculated Ca/P atomic ratio in the precipitate of ALS case was estimated to be 1.6.

Studies on amyotrophic lateral sclerosis by neutron activation analysis--2. Comparative study of analytical results on Guam PD, Japanese ALS and Alzheimer disease cases.

Metal analysis of calcium, manganese, aluminum and copper in CNS tissue samples of degenerative CNS disease cases (six Japanese ALS, three Japanese Alzheimer disease, four Guam PD, one Guam ALS) using neutron activation analysis, was conducted with following results: Five of six Japanese ALS cases, two of three Japanese Alzheimer disease cases and all of four Guam PD cases showed a high content of calcium and aluminum in CNS tissue with a significant positive correlation between calcium and aluminum and/or between calcium and manganese. These findings suggest a possible process of metal-induced soft tissue calcification with interaction of other di- and/or trivalent cations such as aluminum, manganese in CNS tissue of these degenerative CNS diseases.

Wilson's disease; increased aluminum in liver.

Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.