We performed echocardiographic studies in 189 elderly subjects aged over 65. Aortic regurgitation (AR) was detected by real time 2-D Doppler system. 189 patients were classified into 5 groups based on the severity of AR (AR-: 81 pts, AR1+: 32 pts, AR2+: 44 pts, AR3+: 27 pts, AR4+: 5 pts). The diameter of the aortic root, the angle (θ)between the aortic wall and interventricular septum and echo intensity of aortic valve were measured by 2-D echocardiography. There was no relation between the severity of AR and angle θ. Diameters of aortic root were significantly increased in AR3+ cases as compared with AR- and AR2+. Systolic blood pressure was significantly increased in AR4+ cases as compared with AR-, AR1+, and AR2+. Diastolic blood pressure was also decreased in AR3+ cases as compared with AR-. Echo intensity of aortic valve was increased in patients with AR. It was thought that increased diameters of the aortic root in patients with severe AR were induced from the long-standing AR, and that increased systolic blood pressure and decreased diastolic blood pressure in severe AR were caused by hemodynamic changes due to AR. Therefore, we concluded that AR in the elderly was caused by degeneration and/or deformity of the aortic valve.

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The medical records and autopsy data of patients over the age of 70 years at death with a diagnosis of cortical artery infarction (CAI) in the Yokufukai Geriatric Hospital were reviewed. Among 690 autopsied cases from 1981 to 1988, there were 45 cases (21 men and 24 women) with CAI available for this study. Fourteen cases (31.1%) suffered CAI while hospitalized for another disorder. Their ages at death ranged from 70 to 102 years with a mean of 82.4 years. From the results of this neurological and psychological analysis, the residuals of senile stroke were classified into six subtypes;1) cerebrovascular dementia, 2) cerebrovascular Parkinsonism, 3) pseudobulbar palsy, 4) chronic stage of aphasia, 5) slowly-progressive decreased motivation or spontaneity without dementia, 6) the so-called bedridden state (prolonged vegetative or apallic state). Sixty-nine percent had anamnetic hypertension before the stroke. The ages at which they became bedridden ranged from 69 to 102 years with a mean of 81.8 years. Within one year after becoming bedridden, 83.3% of all patients died. The bedridden state in the elderly with residual CAI indicated a poor prognosis within one year after stroke. Causes of death included brain death in 22.3% of all patients, pneumonia in 20.0%, and digestive bleeding in 8.9%.

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Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acethylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acethylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean±SD age of 77.5±8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (³H-QNB), an antagonist for muscarinic acethylcholine receptor, to the rat synaptic membrane, was 18.1±7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7±3.8%). However, that in the VD group (8.4±6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on ³H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r=0.480, p<0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.

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Based on 45 normal cases aged from 32 to 106 years of age, a morphometric study revealed that, despite descrease in the number of both pigmented neurons (PN) and the non-pigmented neurons (NN) with advancing age, the ratio (PN/NN) did not change (4.8). It is well-known that both the substantia nigra and the striatum send fibers to each other. McGee demonstrated that the ratio of the number of large neurons to that of small neurons was constant, irrespective of different ages, although number of both neurons decreased with ageing. It was therefore apparent that this phenomenon in the putamen was the same as in the substantia nigra. It could be considered that “balanced depopulation of different neurons” in the nucleus of the strio-nigral circuit contribute to support normal extrapyramidal functions. Additionally, the centenarian cases showed larger numbers of both PN and NN than younger case. It was likely that they could be classified as socalled “excellent” centenarians. On the other hand, idiopathic Parkinson's disease (15 cases) showed that while the same number of NN remained as in age-matched controls, PN showed marked depopulation. Olivopontocerebellar atrophy of the sporadic type (OPCA, 10 cases) and progressive supranuclear palsy (PSP, 5 cases) showed a decrease in number of both PN and NN. However, NN in PSP showed much more decrease than OPCA. NN sends fibers to the pontine tegmentum as well as the thalamus, and PSP shows marked atrophy of the brainstem tegumentum. In this connection, it was considered that marked decrease of NN in PSP could be related to tegmental artrophy.

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The authors compared the characteristics of the early-onset subtype of Alzheimer's dementia (AD) with those of the late-onset subtype (SDAT) to determine whether Alzheimer's dementia (AD/SDAT) can be divided into two different diagnostic categories. In this study, AD refers to Alzheimer's in which the onset of disease occurred before 65 years of age; and SDAT refers to cases in which onset of illness occurred at age 65 or more. The studied parameters were distribution of age at disease onset, progression of speed of ventricular dilation, speed of deterioration of Hasegawa's rating scale for dementia (HRSD) score, and lesional pattern on the Japanese revised version of the GBS scale (GBSS-JR). The distribution of age at onset in 258 patients with AD/SDAT showed one peak. These patients included both outpatients and inpatients. A 30-month follow-up study to determine the degree of ventricular dilation was performed in 20 AD and 24 SDAT patients. For CT measurement, the width of the third and lateral ventricle (cella media index) was measured every 6 months after admission. Average ventricle width at admission was matched between the two groups. Twelve and 24 months after admission, the mean cella media index of patients with AD was significantly wider than that of patients with SDAT. In addition a deterioration speed of HRSD scores of 16 AD and 14 SDAT patients was compared every month for 5 months after admission. The average duration of illness and HRSD score at admission were matched in the two groups. Two and 3 months after admission, the average HRSD score of patients with SDAT was better (p<0.1) than that of patients with AD. GBSS JR scores 2 months after admission were compared between 16 AD and 14 SDAT patients. Only the average duration of illness of these patients was matched. In 24 of 38 items (63.2%), the scores of patients with AD were significantly worse than those of patients with SDAT. However, there were no items for which patients with SDAT had worse scores than those of patients with AD. These results indicate that the dilating speed of ventricles and the deterioration speed of cognitive function scores occur significantly faster in patients with AD as compared to those with SDAT. Thus, different clinical management of the two groups may required, regardless of the cause of disease.

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Since dry cough has recently been recognized as a side effect of angiotensin converting enzyme (ACE) inhibitors employed in the treatment of hypertension or congestive heart failure, the incidence of dry cough in elderly patients receiving ACE inhibitors was investigated. There were 237 out-patients on either captopril, enalapril, or delapril, in August and November 1989. Questionnaires concerning dry cough and smoking were completed by 184 patients. Patients either less than 50 years of age, or with chronic pulmonary disease were excluded. The remaining 168 patients, 63 males, 105 females, with a mean age of 73 years were analyzed for the incidence of a dry cough in relation to age, sex, smoking, and type of drugs. The overall incidence of a dry cough was 21/168 (12.5%), 7/63 (11.1%) for males and 14/105 (13.3%) for females, and was less frequent with advancing age; in the 51-60 age group 4/11 (36.4%), in the 61.70 age group 5/39 (12.8%), in the 7180 age group 9/75 (12.0%), in the 81-90 age group 3/40 (7.5%), in the 91- age group 0/3 (0%). Enalapril showed significantly higher incidence of dry cough than captopril (16/93, 17.2% vs 7/88, 8.0%, p<0.05). Delapril showed an incidence 4/11, 36.4%, however, 9 out of the 11 patients who were given delapril had had a history of a dry cough with captopril or enalapril, and in 4 out of these 9 patients the dry cough disappeared by replacement of captopril or enalapril by delapril. The incidence of day cough was 8.8% for the current smokers (3/22 male, 0/12 female) and 13.0% for the nonsmokers (including exsmokers) (3/30 male, 10/70 female) without significant difference. It was concluded that a dry cough with ACE inhibitors in the elderly patients is less frequent as age advances, regardless of gender, with increased incidence in enalapril than in captopril, and unrelated to smoking history. Dry cough in cases treated by enalaplil or catopril may disappear by substitution with delapril.

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We studied the influence of aging on the stimulatory effect of parathyroid hormone (PTH) to (Ca²⁺+Mg²⁺)-ATPase activity of rabbit renal basolateral membrane (BLM). Stimulated by PTH, (Ca²⁺+Mg²⁺)-ATPase activity of BLM from aged rabbits was lower than those from young rabbits. However, the stimulatory effect of cyclic AMP (cAMP) showed no differences in terms of (Ca²⁺+Mg²⁺)-ATPase activity in BLM from aged and young rabbits. As cAMP production in BLM caused by PTH stimulation was not measured, it is unclear whether cAMP production is different in BLM from young and aged rabbits. From these results, we concluded that in BLM from aged rabbit, the lower effect of PTH on (Ca²⁺+Mg²⁺)-ATPase is due to lower production of CAMP or some other disorder of the PTH signal transduction mechanism. As (Ca²⁺+Mg²⁺)-pump plays an important role in Ca²⁺ reabsorption in kidney, its lower activity in aged rabbit may be one reason for aberration of renal calcium handling.

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The authors have sometimes experienced cases of frozen gait without any other manifestations of parkinsonisms in the elderly, so we examined these cases using MR imaging and SPECT imaging. The group with frozen gait (4 cases, aged 78 to 82 years) which failed to respond to L-dopa therapy, had no limb-kinetic apraxia or frontal signs, but did exhibit “kinésie paradoxale”. The clinical symptoms of case 4 were consistent with so-called “pure akinesia”. CT findings in this group failed to elucidate the pathogenesis of frozen gait. MR imaging of all of the cases except for the case of pure akinesia (case 4) revealed a high signal intensity areas in subcortical lesions (especially the frontal area). Case 4 had only a few spotty high-signal intensity areas. We then compared 6 cases which have the same lesions (on MRI) as cases 1-3 without frozen gait in cases 1-3 using ¹²³I-IMPS PECT. Relatively low accumulation of radionuclide in the frontal area was observed in these cases. Case 4 had a slightly low perfusion area in the frontal lobe. However in the patient treated with L-threo-DOPS, accumulation of radionuclide in the frontal area increased slightly after L-threo-DOPS therapy. It appears that one of the reasons for frozen gait in the elderly is incomplete infarct of the subcortical white matter with a low perfusion area in the frontal cortex. Furthermore, in some cases of frozen gait it is difficult to distinguish between cases with white matter disorders and cases of pure akinesia on the basis of clinical symptons and CT alone.

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The effects of a two-week high sodium diet on mitral flow pattern were assessed in 29 patients with essential hypertension (81.9±6.9years). Transmitral flow was recorded during different rates of salt intake; 7g/day for 8 weeks and 20g/day for 2 weeks. With sodium loading, 25 patients whose mean blood pressure (MBP) increased by 10 percent or more were termed saltsensitive (SS) group, and 4 patients whose MBP did not change or increased by less than 10 percent were termed non-saltsensitive (NSS) group. with mitral flow velocity integral, cardiac output (CO) and total peripheral resistance (TPR) were calculated. Thirteen of the SS patients were defined as “SS_T” in which an increase in TPR was greater than that in CO with sodium repletion. In the remaining 12 SS patients termed “SS_C”, the increase in CO was greater than that in TPR with salt loading. CO increased significantly in the SS_C patients, but did not change in the SS_T or NSS group with sodium loading. TPR increased significantly in the SS_T and NSS subjects, and decreased significantly in the SS_C patients. Peak velocity of transmitral flow in the rapid filling phase (R) decreased significantly in the SS_T and NSS patients, and increased significantly in the SS_C group. On the other hand peak velocity of transmitral flow in the atrial contraction phase (A) increased significantly n the SS_T and SS_C groups, but remained unchanged in the NSS patients. There was a significant increase in A/R in the SST group and a significant decrease in A/R in the SS_C patients with sodium loading.

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Three elderly patients, (an 80-year-old female, 78-year-old female and 78-year-old male) suffering from renal cell carcinoma with pancreatic metastasis were reported. In all cases, renal cell carcinoma had been diagnosed previously. Pancreatic tumors were revealed by computed tomography and ultrasonic study during subsequent admission in all cases. In the first case, laparotomy and histological examination proved that pancreatic tumor was metastatic from renal cell carcinoma. In the other cases, according to their clinical course and other laboratory data, we considered the pancreatic tumors to be metastatics from renal cell carcinoma though histological diagnosis was not obtained.

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