Cerebral blood flow and metabolism in 25 patients with multiple cerebral infarcts (14 with dementia) and 5 healthy age-matched controls were measured to investigate the difference in cerebral blood low (CBF) and cerebral oxygen cosumption (CMRO2) between patients with dementia and patients without dementia. None of the patients had any lesions in the cortex, but all had multiple lesions in the basal ganglionic region, and in the white matter, according to CT images. CBF, CMRO2 and oxygen extraction fraction were measured by positron emission tomography (PET) using the 15O2, C15O2 steady state inhalational technique. In patients with multiple cerebral inarcts the absolute values of CBF and CMRO2 were decreased significantly from normal control values, and there was no significant difference in the absolute values of CBF and CMRO2 between patients with dementia and patients without dementia. In most patients with dementia, relative values (regional value/ mean cortical value) of CBF and CMRO2 decreased in the frontal and the parietal cortex. Four patients had repeated PET studies. In two of them, decrease in CMRO2 was preceded by decrease in CBF. These results suggest that dysfunction of frontal cortex and parietal cortex, and chronic ischemia might be related to the occurrence of dementia in patients with multiple cerebral infarcts, which were in the basal ganglia and the white matter.
In vivo studies of nerve tissue of senescent animals have raised the possibility that initiation and elongation of axonal processes in regeneration are somehow altered by aging. However, this has not been examined in dissociated cell culture because of technical difficulties. The present study was performed to compare the effects of nerve growth factor (NGF) and gangliosides mixture (Ggl) on neurite elongation of dorsal root ganglion (DRG) cells from senescent mice with those from young adult mice. DRG neurons were obtained from male mice of the 72-week-old (Group O) and of the 10-week-old (Group Y). Dissociated neuronal cells of each group were cultured for 4 days in chemically determined serum-free medium including various levels of 7S-NGF up to 160ng/ml or of Ggl up to 20μg/ml. After immunohistochemical identification of neuronal cells, neurites with two kinds of lenghts, maximum length (ML; length of the longest neurite belonging to the indivudual neuron) and total length (TL; summation of length of all neurites belonging to that) were quantified as elongated neurites. NGF showed concentration-dependent neurite elongation in ML and TL of Group O and Y. Ggl increased TL at relatively low levels in both groups but no significant changes were detected in ML. On the other hand high levels of Ggl did not show any enhancement in ML or in TL. These results indicate that the effects of NGF and Ggl were not altered by aging, as far as elongation of neurite was concerned. In addition to biochemical deterioration of the neuron itself, decreased release of neurite-promoting factors such as NGF and Ggl from target cells of the neuron and surrounding cell may account for the reduction of capacity for neurite regeneration in aged animals.
Clinical evaluation of aortic atherosclerosis has been most commonly performed by visual analysis of aortic calcification on conventional radiographs or X-ray CT. However, precise evaluation of the degree of calcification or mild changes with increasing age can be difficult by these methods of visual analysis. A new quantitative method of evaluating the abdominal aortic atherosclerosis using CT is reported. Target CT scans of the abdominal aorta were performed at the level of the 1st, 3rd and 4th lumbar vertebrae. Two circular regions of interest (ROI) were selected along the outer margin and inner margin of the abdominal aortic wall on CT images, since it was difficult to precisely trace the aortic wall. Histograms of CT value for each pixel were made from two ROIs. A histogram at the ROI of the outer margin was depicted using class values over the maximum CT value in histogram at the ROI of inner margin which indicated flowing blood. A sum of products of the value in each class by the number in that class was divided by the aortic diameter. The value thus obtained was defined as the atherosclerotic index (S.I.). Forty-five cases were studied with this method. Six cases were excluded because of artifacts. The remaining 39 cases (16 males, 23 females) were analyzed. S.I. increased with aging and was higher in men than in women. However, it increased more rapidly in women (8.68/year) than in men (2.73/year). Because this new method employed the CT value, it is more objectively quantitative than previous methods of visual analysis in evaluating abdominal aortic atherosclerosis. This method has potential for the analysis of slight changes with increasing age or for therapeutic effects in cases of atherosclerosis.
Premature development of atherosclerosis is a fatal complication together with cancer in patients with Werner' syndrome, a known syndrome of premature aging. Proliferation of arterial smooth muscle cells (SMC) is a key event in the formation of atherosclerosis. This paper studied the serum growth promoting activity of Werner's syndrome in cultured rabbit aortic SMC. Serum of cases of Werner's syndrome showed significantly higher growth-promoting activities than those of age-matched cntrols. The levels of serum growth hormone, plasma somatomedin C, and urine epidermal growth factor were not increased in Werner's syndrome. The level of serum insulin was generally increased in Werner's syndrome. However, there was no correlation between serum insulin level and growth promoting activity, and the effective dose of insulin for the promotion of SMC growth was ten thousand times higher than that contained in the serum. The above results suggest that elevated serum growth-promoting activity in Werner's syndrome is in part responsible for the premature atherosclerosis and that this elevated activity is derived from either platelet derived growth factor or an unknown growth factor(s) contained in the serum.
The authors evaluated the changes in the scores on Hasegawa's rating scale for dementia (HRSD) of demented patients in a hospital for dementia. The subjects in this study were 69 patients (12 males and 57 females) including 34 with dementia of the Alzheimer type (DAT), 30 with multi-infarct dementia (MID) and 5 with mixed dementia. Their average age was 75.6 years and the mean period after symptom onset was 2.5 years. The observation period was 5 months after admission to the hospital. We rated HRSD on admission and each month after admission. During the observation period, 65 patients received drugs orally and 65 patients were given rehabilitation for impaired cerebral function. We tried to classify the pattern of change in the HRSD into 5 groups as follows; 1) no remarkable change or deterioration, 2) wavering, 3) improvement during only the first month, 4) improvement from the first month after admission, 5) improvement from admission. We assumed that the patients in group 3) had been underestimated on admission. Their mental states might have been confused on admission because of the change in their living environment. Thus we rejected this group for statistical analysis and compared the madical characteristics of those in the non-improved group (1 and 2) with those in the improved group (4 and 5). The period from onset of symptoms in the improved group was shorter than in the non-improved group (p<0.05). Moreover there was a tendency (p<0.1) toward less abnormal findings in the EEG and less cerebral atrophy on CT scan in the improved group. Indeed, many DAT cases who were thought to be resistant to therapy were included in the improved group. These results indicate the necessity of admission for therapy of dementia at an early stage, the importance of adequate care by well-trained staff and a good environment in which patients can receive psychorehabilitation.
In all autopsied cases from Januray 1980 to June 1988 (56∼102 years old, 243 men and 307 women), cardiac rupture death was observed in 14 cases out of 68 deaths of acute myocardial infarction in our hospital. Cardiac rupture occured in 2, 4, 3, and 5 cases in their 60's, 70's, 80's, and 90' respectively, and 4 in men and 10 in women. Complaints of chest pain were present in 4 cases. Cerebrovascular disease was present in 9 cases and hypertension in 7. In 9 cases, the thickness of the ruptured wall was over 14mm. The location of the ruptured lesion was the anterior wall in 4 cases, anteroseptal in 3, anterolateral in 1, lateral in 1, posterior in 1, and apical in 1. In conclusion, the incidence of cardiac rupture was higher in female than in males, and in silent myocardial infarction than in painful one. The location of rupture was frequently in the anterior or lateral wall. Aging and hypertension would not be a worsening factor in the pathogenesis of cardiac rupture in myocardial infarction, but cerebrovascular disease might be a risk factor in respect to masking occurence of myocardial infarction.
The number of the nerve cells, appearance of Alzheimer's neurofibrillary tangles and of senile plaques in the hippocampus of 100 female autopsy cases aged 56∼101 were compared in relation to age and grade of dementia. The number of nerve cells of granular and pyramidal layers decreased significantly with age, however, the decrease in number did not necessarily correlate with the grade of dementia. Appearance of Alzheimer's neurofibrillary tangles was increased in grade with age and with grade of dementia of all types. Appearance of senile plaques increased in grade only in cases with dementia of Alzheimer's type, but not in case with cerebrovascular type of dementia.
The amount of autofluorescent granules of nerve cells of the hippocampus and cerebellum in 92 female autopsy cases aged 56∼101 was micrometrically compared with regard to their age and grade of dementia. Highly significant differences were found in the amount of pigment between the nerve cells of the granular and pyramidal layers of the hippocampus and between Purkinje cells and dental nuclear cells of cerebellum. No significant difference, however, was observed according to age or to grade of dementia.
With the increase in the aged population, it is expected that the number of debilitated aged people will increase and that the number of patients receiving many medications will increase. However, there have been few reports of clinical pharmacological studies on blood pharmacokinetics, metabolism, advers effects, etc, of drugs used in debilitated aged people who have lowered physical and mental functions complicated by many diseases. Thus, for the large part, pharmacokinetics in these patients remains unelucidated. We experienced eight cases of marked hypoglycemia of unknown cause in patients who had not taken any hypoglycemic drugs or insulin and examined the relationships between the event and the physical features and medications of the patients. The eight patients included both males and females aged 66 to 88 years (mean: 78.5 years). The eight patients were all aged and showed cerebral infarction, reduced volition, etc. The onset of hypoglycemia was preceded by decreased appetite and an abrupt manifestation of severely disturbed consciousness a few days previously. Laboratory tests revealed marked hypoglycemia in 8 cases, leucocytosis in 7 cases (not examined in one case), metabolic acidosis in 3 cases, elevated GOT in 5 cases, elevated GPT in 2 cases, increased BUN in 1 case, and positie CRP in 4 cases. The patients had been taking an agent to activate brain metabolism/improve mental symptoms (Hopantene calcium: 7 cases; Idebenone: 1 case). The Idebenone-treated patient had received Hopantene calcium for eleven months prior to receiving Idebenone. Furthermore, the findings resembled those of Reye's syndrome often noted in children. The above results suggested that Hopantene calcium, a frequently used brain metabolism/mental symptom improver, might in some way be involved in causing glycogenetic system disorder leading to the onset of hypoglycemia. It is considered uregently necessary to investigate the causal relationship of Hopantene calcium with Reye's syndrome and also the blood pharmacokinetics in aged patients with multi-organ disorders.
The Japanese version of the GBS Scale (GBSS-J) was administered to 246 elderly patients with dementia in a geriatric hospital to test the inter-rater reliability and validity of the items and the subscales of the GBSS-J. The inter-rater reliability of the 26 items was tested by rating 20 patients. After the raters conferred with each other how to rate the items of the scale, the items were rated independently. Pearson's correlation coefficients indicating the agreement between the rates were as good as more than. 660 except for the items of impaired wakefulness and confusion. The validity of the 28 items was examined by comparing them with the stages of Functional Assessment Staging (FAST). Hasegawa's dementia scale (HDS) was employed as an external standard to test the items of the subscale of intellectual functions. Physical disability was checked by using the Rapid Disability Rating Scale (RDRS). Mean scores of the 20 items except for the 6 items included in the subscale of different symptoms common in dementia significantly increased as the FAST stage advanced. These results indicated that the 20 items of the GBSS-J measured the severity of dementia with sufficient validity. In addition, according to the results of analysis of variance and covariance, the items of motor insufficiency in taking food, impaired physical activity, impaired wakefulness and irritability were related to the severity of physical disability rather than that of dementia. Aslo, the 10 items of the subscale of intellectual functions showed significant correlations with the scores of HDS, while the item of impaired wakefulness showed a significant, although fairly low correlation. In the partial correlation controlled with eating, walking, bathing, dressing and excretion in RDRS, no significant correlation with scores of HDS was obtained with the item of impaired wakefulness. This finding supports the above mentioned results. Cronbach's α was used to test the internal reliability of the 4 subscales of the GBSS-J. Cronbach's αs of the subscales of motor functions, intellectual functions and emotional functions were as high as .938, .958 and .818, respectively, while that of different symptoms common in dementia was as low as .716. These findings indicated the 3 subscales other than that of different symptoms common in dementia showed sufficiently high internal reliability. As for the relation between the total scores of the 4 subscales and the stages of FAST, Spearman's correlation coefficients were as high as .791 in the subscale of motor functions, .987 in intellectual functions, and .769 in emotional functions, while that of different symptoms common in dementia was as low as .213. Pearson's correlation between the scores of HDS and the total scores of intellectual functions was as high as -.866. In factor anlaysis with 26 items to test the construct validity of the 4 subscales, 5 factors emerged. The original 4 factors, i.e., 4 subscales were not confirmed. The above mentioned results indicated that the reliability and validity of the items comprising the GBSS-J were sufficient apart from the several items, to measure the severity of dementia. However, the construct validity of the original 4 subscales which is very important in developing scales for the aged was not confirmed in the present study.
The degree of PVHIS (periventricular high intensity signal) on the MRI was composed with the permeability of brain blood vessels using the cerebrospinal fluid (CSF)/serum ratio for albumin, and the CSF/serum ratio for IgG in elderly patients. The 47 elderly patients (mean age=79.9) were divided into three groups: (1) Mild group (20 cases, M:6, F:14, mean age=75.8), (2) Moderate group (18 cases, M:7, F:11, mean age=82.6), (3) Severe group (9 cases, M:2, F:7, mean age=82.9), in accordance with the degree of PVHIS on the MRI. The MRI was operated at a field strength of 0.22 tesla. The pulse sequence (used on all patients) had a repetition times (TR) of 2, 000msec and a time to echo (TE) of 40msec. The levels of albumin and IgG in the serum and CSF were measured. The CSF/serum ratio for albumin was used of analyze the permeability of the brain blood vessels in each group. There was no significant difference in the level of the serum albumin, the CSF albumin, the serum IgG, the CSF IgG and the CSF/serum ratio for IgG among the three groups. The same was found to be true for the IgG index which indicates the synthesis of immunoglobulin in the central nervous system. However, there was a statistically significant difference (p<0.05) in the CSF/serum ratio for albumin between groups (1) and (3). The increased CSF/serum ratio for albumin in the severe group indicated there were confluent lesions involving the entire extent of the periventriular white matter on the MRI. This suggested an increased permeability of brain blood vessels which revealed the dysfunction of the blood brain barrier due to affected cerebral endothelial cells in capillaries.
To demonstrate that muscarinic acetylcholine receptor (mAChR) acts as an aging marker, we studied whether receptor binding capacities decreased with age. A potent muscarinic cholinergic ligand, N-methyl scopolamine (NMS), was used to detect how the binding capacities (Kd, Bmax) of the receptor changed with age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for the [3H]-NMS. Both groups of healthy female adults (40∼49 years old, N=27) and probable Alzheimer's patients (54-71 years old, N=17) were examined. For the healthy controls, the regression equations are: Y=12.2X-272.6 (Kd; r=0.453, p<0.05) Y=401X-16, 302 (Bmax; r=0.387, p<0.05) in which, X and Y respectively represent the age of individuals and Kd (or Bmax). Hence, for patients with Alzheimer's disease, the correlations between Kd and age, and between Bmax and age, were weak (r=0.021, 0.032, not significant, respectively). Three age groups from healthy female adults were examined: 40-49 (N=9), 50-59 (N=8) and 60-69 years old (N=10). There were significant differences (p<0.05) between age groups 40∼49 and 60-69 years old in both Kd and Bmax. Furthermore, significant change (p<0.05) with Bmax was obtained in lymphocytes from patients, compared to age-matched controls. These results suggest that muscarinic cholinergic binding by lymphocytes may serve as a useful peripheral marker, reflecting alterations associated with aging.
A case of Crohn's disease in the elderly complicated with internal fistula and mass formation was reported. A 62-year-old woman was admitted to National Toyohashi Hospital on August 16, 1986, with complaints of abdominal pain, pyrexia and diarrhea for two months. Physical examination revealed a goose-egg sized mass in the left lower quadrant of the abdomen. Barium meal examination of the small intestine showed strictures and fistula formation of the jejunum. Angiography showed narrowing and irregularity of the vessels. Malignant tumor of the small intestine could not be ruled out, so that an exploratory laparotomy was done on October 14, 1986. At operation, the jejunum, 70cm from the ligament of Treitz, formed a 5×7cm mass with adhesion and fistula formation. There was a skip lesion at the terminal ileum. Forty cm of the jejunum and 60cm of the ileum were resected, and both of the resected specimens showed longitudinal ulceration, cobblestone appearance and thickening of the wall. Histological examination showed noncaseating granulomas with epitheloid cells and giant cells in the tunica muscularis. Since the report by Komi et al. in 1970, 13 cases of Crohn's disease in the elderly have been reported in Japan up to 1988. We summarized the characteristic findings of Crohn's disease in the elderly in Japan as follows; 1) Clinical symptoms and radiographic findings were similar to those in younger patients. 2) Small bowel involvement was reported in 54%. 3) Surgery was performed in 46%. 4) Preoperative diagnosis was only made in 46% of the elderly patients. 5) There was no associated perianal disease. We conclude that Crohn's disease, which is common in the young, should be considered even in the elderly.