Marked advances in the treatment of neurological disorders which affect the elderly have been established in recent years. Cerebrovascular disorders including stroke and vascular dementia are still among the most frequent diseases in the Japanese elderly. For treatment of hypertensive patients with or without a history of stroke, slight decrease of blood pressure (BP) is recommended since recent PET studies have revealed that an excessive drop of BP markedly decreases cerebral blood flow. Furthermore, 24-hour-monitoring of BP revealed that physiological fluctuation of BP consisting of high daytime BP and low nocturnal BP disappears in hypertensive patients with vascular dementia and those with non-symptomatic vascular lesions on MRI. Recommendable BP levels for the hypertensive elderly must be established. The efficacy of both aspirin and ticlopidine for prevention of stroke has been established. Recent multi-centric trials have revealed that ticlopidine is more effective in preventing stroke but has more dangerous adverse effects than aspirin. Aspirin is reported to improve both the intellectual scale and cerebral blood flow in vascular dementia. In Parkinson's disease (PD), L-DOPA therapy, usually in combination with a dopa decarboxylase inhibitor, is common. Other dopaminergic drugs including bromocriptine, lisuride and pergolide are used clinically or are being studied. Recently selective monoamine oxidase (MAO) B inhibitors have been used in order to slow clinical progression of the disease, in addition to an attempt to increase the potential of dopamine through inhibition of MAO. Neural transplants to the striatum of PD were first applied using autografts of the adrenal medulla in 1985, but resulted in transient or only slight improvements. In 1990, Swedish researchers reported that grafts of fetal dopamine neurons survived and improved motor function in PD. Fetal neuronal grafts seem to be promising in the treatment of PD though both biological and medicoethical matters must be solved. Although several trials of treatment of Alzheimer type dementia (ATD) have been carried out, with anti-cholinesterase agents such as physostigmine and tetrahydroaminoacridine or with other neurotransmitters, satisfactory results have not yet been obtained. Recent studies linked familial Alzheimer's disease and deposition of β-protein with the 21 chromosome. Gene biology may provide new ideas for the treatment of ATD. Several other new therapeutic methods for the treatment of neurological disorders including botulinus toxin for involuntary movements in the face and neck, immunotherapy for Lewis-Sumner syndrome, and aciclovir for herpes simplex encephalitis were described.

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Bone and calcium metabolism was investigated in genetically obese, diabetic db/db mice and compared with that in a new hypoglycemic agent (AS-6) treated db/db mice and in their lean litter mates as controls. The 5-week-old db/db mice (serum Ca 9.88±0.22mg/dl, glucose 258.6±13.3mg/dl) were randomly divided into two groups. One group, together with their lean litter mates, was fed a commercial diet (CE-2). The other db/db group was fed CE-2 diet containing 0.1% of AS-6. Both groups were fed for 20 weeks. The serum glucose and calcium levels in db/db control groups (serum Ca 12.3±0.1mg/dl, glucose 650.2±23.9mg/dl) were higher than those in lean control groups (Ca 9.8±0.2mg/dl, glucose 180.7±10.1mg/dl). The wet, dry and ashed weights of the femur in db/db control were significantly lower and the length of femur in db/db control was significantly shorter than those of lean controls. These data suggest that retarded bone growth in db/db mice is related to progression of diabetes. Although, there was no change in Ca/P, Ca/ash and total perimeter in femurs, the cortical area in the femurs of db/db control mice (0.65±0.02mm²) was significantly smaller than that of the femurs of lean control mice (0.74±0.02mm²). The cortical bone thinning observed in the db/db control could have been caused by increased bone resorption. Treatment with AS-6 for 20 weeks resulted in a 48.6% decrease of serum glucose and 5.2% decrease of calcium as compared with db/db controls. The ratios of dry/wet weight and water/wet weight in the femurs of db/db mouse were improved by AS-6 treatment. The cortical area in femurs of AS-6 treated mice (0.71±0.01mm²) was significantly larger than that in db/db controls. These data suggested that NIDDM model db/db mice had retarded bone growth and increased bone resorption, and that hypercalcemia found in NIDDM animal models could have resulted in the release of calcium from bone tissue. Furthermore, reduction of blood glucose levels by AS-6 treatment could improve abnormal bone metabolism and prevent of bone thinning.

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Lacunes on brain MRI, casual blood pressure, 24-hour ambulatory blood pressure and common carotid blood flow measured by the doppler method were studied in 31 elderly patients with Parkinson's disease (mean age 67.5 ±7.3 years). Nineteen patients with Parkinson's disease (61%) had at least one lacune. Patients with lacunes (P(+)) were significantly higher in age than patients without lacune (P(-)). The difference of casual blood pressure between patients in the two groups was not significant. On the other hand, the average of ambulatory blood pressure measurements during a 24-hour period was significantly higher in the P(+) group than in the P(-) group. The average of carotid blood flow was also significantly lower in the P(+) group than in the P(-) group, however, after adjustment for age, the difference between them became insignificant. In conclusion, the incidence of silent lacunes on brain MRI was fairly common in elderly patients with Parkinson's disease. A high average 24-hour ambulatory blood pressure was suggested to be one of the risk factors of lacunar stroke in elderly cases of Parkinson's disease. The concept of “combined type” in Parkinsonism was supposed to be suitable as well as in senile dementia of Altzheimer type.

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This study was conducted to examine the nocturnal ventilatory parameters and gas exchange in the elderly with nocturnal disturbed breathing. In order to facilitate analysis of ventilatory parameters with minimum manpower, we developed an unattendant continuous nocturnal monitoring system for ventilation and arterial oxygen saturation. Using this system, nocturnal ventilatory parameters and gas exchange were investigated in our geriatric ward. We investigated 30 elderly subjects aged between 65 and 94 (mean age 77.8±6.5 years, male; female=15:15). The subjects were free of severe cardiovascular and cerebrovascular disorders, and underwent 10 hours of continuous monitoring of ventilation and arterial oxygen saturation (Sa_O2). Number of significant desaturation (SDS; desaturation greater than 4% in Sa_O2 from the baseline value) and desaturation index (DI; ΣSDS(%)×duration(hour)) were calculated using the same system. The number of apnea episodes significantly correlated with DI and the number of SDS. DI also significantly correlated with lowest Sa_O2, while the number of SDS and the number of apneas were not found to be correlated with lowest Sa_O2. The number of SDS and the number of apnea episodes did not correlated with lowest Sa_O2. From the view point of gas exchange during the night, newly introduced DI is more comprehensive parameter when compared with the number of apneas or SDS. Subjects with a DI of over 0.5 were assigned to the group A (n=8, mean age=77.8) and the remaining subjects were assigned to group B (n=22, mean age=77.8). We compared the group A with the group B regarding nocturnal ventilatory parameters and Sa_O2. The group A had significantly smaller ventilatory volume during sleep than the group B, while there were no difference in pulmonary function tests during day- time. The mean inspiratory flow of the group A also significantly decreased, compared with the group A. Additionally, the lowest Sa_O2 of the group A was significantly lower than that of the group B, while there was no difference in baseline values between the group A and the group B. Therefore, DI can be useful for characterization of nocturnal disturbed breathing in the elderly. However, further studies are needed to clarify the usefulness of DI in health and disease.

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Serum lipid, lipoprotein, apolipoprotein, and sterol profiles were studied in 22 patients with senile dementia of the Alzheimer type (SDAT) and 29 patients with vascular dementia (VD). Levels of high density lipoprotein-cholesterol (HDL-C) were lower in both patients groups of SDAT and VD than in control group. Apolipoprotein AI and AII are two major proteins in HDL. In this study, apolipoprotein AI levels were normal, but apolipoprotein AII levels were lower in the patient groups, especially in the VD group, than in the control group. Lipoprotein (a) levels were higher in both patient groups, especisally in the VD group. There were no differences of cholesterol, cholesterol precursors (desmosterol and lathosterol), and plant sterols (campesterol and β-sitosterol) among the three groups. Murine apolipoprotein AII is a serum precursor of marine senile amyloid protein, and the apolipoprotein AII variant with proline→glutamine substitution at position 5 in the serum of accelerated senecence-prone mice is identical to the murine senile amyloid fibril protein from amyloid-deposited tissues of these mice. In human SDAT and VD, the reason for the low level of apolipoprotein AII remains unclear.

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The authors experienced 4 cases of calcified postinfarction aneurysm of the left ventricle. They were all male, aged 55 to 71 (mean 64). Risk factor for coronary artery disease was only smoking in 2 patients, but there was none in the others. They had had acute anteroseptal or extensive anterior infarction at age 41-57 years (mean 49.3), and associated major cardiac events 10-22 years (mean 14.5) after acute myocardial infarction. Ventricular tachycardia, congestive heart failure and systemic thromboembolism were seen in 4, 2 and 1 patients respectively. However, none developed angina pectoris. In the 2 patients in whom signal-averaged electrocardiogram was performed, late potential was detected, so it was suspected that ventricular tachycardia could be due to reentry. Left ventricular end-diastolic pressure was elevated in all patients except one and ranged from 11 to 22mmHg. Left ventricle was dilated in all cases and the end-diastolic volume index ranged from 143 to 503ml/m². The left ventricular ejection fraction ranged from 11 to 24%. However, in 2 of the 4 patients, the cardiac index was within normal limits, and evidence of congestive heart failure was absent. In 2 other patients with associated congestive heart failure, cardiac indices were 2.32, 1.56l/min/m² respectively. Coronary arteriogram showed a total occlusion in the left anterior descending (LAD) artery in all cases, and only the LAD artery was affected in 2 patients. In the remaining 2 patients, the right coronary arteries also were significantly stenotic or totally occluded, i.e., they had 2-vessel disease. One of 4 patients underwent an emergency aneurysmectomy of the left ventricle because of refractory ventricular tachycardia, which disappeared after the operation. To our knowledge, this is the first case of calcified postinfarction aneurysm associated with lethal ventricular arrhythmia following a successful operation. One died suddenly during fishing, and the another one died of pneumonia about 10 days after ventricular tachycardia with a shock. Moreover, the remainder died of septic shock complicated by pneumonia.

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A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5g/dl, WBC 4.6×10⁹/l with normal differentiation and platelet 2×10⁹/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thromboytopenia. High dose intravenous immunoglobulin (400mg/kg/day for 5 days) and bolus methylprednisolone (1g/day for 3days then tapered) were administered, starting on March 13. Her platelet count had increased immediately on March 20 to 40×10⁹/l. However, platelet count decreased to 4× 10⁹/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200×10⁹/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15×10⁹/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.

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Two autopsy cases of aortitis syndrome (Takayasu's aortitis) in the elderly are presented. Case 1 was an 81-year-old woman in whom hypertension was observed at age 37, and difference of right and left arm blood pressure was pointed out at age 65. She was referred to the authors' hospital at age 72. Chest X-ray and computed tomography of the thorax indicated atypical coarctation and diffuse calcification of the aorta. Case 2 was a 69-year-old woman in whom hypertension was pointed out at age 49, and blood pressure in the arms was found to differ from that in the legs at age 63. Chest X-ray and computed tomography showed diffuse calcification and marked narrowing of the descending aorta. Pathological examination revealed marked calcification in the thickened adventitia of the aorta with mild atherosclerotic change. Irregular fibrotic changes of the adventitia and degeneration of elastic fibers of the media of the aorta were noted in both cases, and were consistent with Takayasu's aortitis. This disorder is common in young women and only a small number of elderly cases are reported although its incidence is increasing. Diffuse calcification of the aorta with an absence of inflammatory signs, which is frequent in older patients, were observed in both case. Systemic hypertension is the most important risk factor with coarctation of the aorta in Takayasu's aortitis. Bypass surgery is recommended in young patients, however in elderly patients, it is generally avoided, in favor of medical control of hypertension.

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Three cases of Chilaiditi's syndrome are reported. Case 1: A 56-year-old woman was admitted with dysphagia. She had been suffering from progressive systemic sclerosis for 16 years. Three years before the admission, dysphagia developed and dilatation and hypomotility of the esophagus were observed. Chest and abdominal x-ray films on admission showed severe dilatation of the intestine, pneumatosis cystoides intestinalis, abdominal free air, and Chilaiditi's syndrome. Chilaiditi's syndrome and other signs disappeared after conservative treatment. She died four months later due to cor pulmonale. Case 2: An 87-year-old man was admitted with constipation and left lower abdominal pain. Physical examination showed ascites. Chest and abdominal x-ray examination showed Chilaiditi's syndrome. Cytological examination of ascites revealed adenocarcinoma cells. Diagnosis of peritonitis carcinomatosa due to cancer of pancreatic tail was made. Chilaiditi's syndrome disappeared after removal of ascites. Case 3: A 71-year-old bedridden man who had urinary incontinence developed meteorism. Repeated chest x-ray examinations constantly showed Chilaiditi's syndrome. He died of pneumonia two years later. The pathogenesis of Chilaiditi's syndrome was discussed and the literature was reviewed.

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A 73-year-old man was admitted with gait disturbance and dysarthria. He showed right-side cerebellar ataxia. Computed tomography of brain showed left thalamic bleeding. Nine months later, he was admitted again because of siezure and consciousness disturbance. He had a history of diabetes mellitus and gout for five years, but no hypertension. On physical examination the lungs and heart were normal. On neurological examination, he showed stupor. pupils and eye position were normal. He showed right hemiparesis and urinary incontinence. The deep tendon reflexes were (+) at the upper limbs and (++) at the right knee and ankle. Blood pressure was 162/88mmHg and glucose was 275mg/dl. Other laboratory data were normal. Brain CT showed hemorrhage of the left frontal lobe. The cystatin C level in cerebrospinal fluid was 68ng/ml. Therefore we suspected cystatin C deposit amyloid angiopathy. In this case, thalamic hemorrhage was initially thought to be amyloid angiopathy. In cases of cerebral hemorrhage in the elderly without hypertension, we must be considered amyloid angiopathy.

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