[in Japanese]

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In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean±SEM, 71±1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP≥160mmHg and DBP≥95mmHg, 70±1 years) and 11 had isolated systolic hypertension (ISH: SBP≥160mmHg and DBP <95mmHg, 74±2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174±3/97±1 to 149± 4/84±2mmHg in EH and from 167±3/82±2 to 144± 4/74±2mmHg in ISH. LVMI was significantly reduced from 204±14 to 174±16g/m² in EH and from 179±14 to 156±12g/m² in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r=0.74, p<0.05). In EH, there was no significant relation between BP and LVMI changes. The changes in circulatory hormones and those in LVMI did not correlate. In these elderly hypertensive patients, the antihypertensive treatment with Ca antagonist or ACE inhibitor decreased BP sufficiently with monotherapy, and reduced cardiac hypertrophy without any deterioration of left ventricular function in either EH or ISH. It was suggested that the reduction of systolic pressure load might contribute to the reversal of cardiac hypertrophy in ISH.

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To determine the diagnostic accuracy of single photon emission computed tomography (SPECT) with ¹²³I-IMP in Alzheimer-type dementia (ATD), we studied 46 ATD patients and 23 healthy controls. The patients fulfilled the NINCDS-ADRDA criteria for probable or definite ATD and were classified as having mild, moderate, and severe ATD by neuropsychological examinations. To assess regional cerebral blood flow, we performed qualitative SPECT image analysis without any knowledge of the subject's clinical classification. The image was regarded as abnormal if cerebral blood flow was reduced in the unlilateral or bilateral temporoparietal association areas, with or without any reduction of flow in other brain regions. The diagnostic sensitivity (abnormal image/patient) of ¹²³I-IMP SPECT in mild, moderate, and severe ATD was 67%, 86%, and 92%, respectively. The specificity (normal image/control) was 91%, because an abnormal image was found in only 2/23 healthy controls. Eight ATD patients without reduced temporoparietal perfusion showed normal perfusion or frontal hypoperfusion. These results suggest that ¹²³I-IMP SPECT may provide an accurate and sensitive diagnostic marker for ATD. The detection of these characteristic abnormalities of cerebral perfusion could well be applied to the clinical diagnosis of ATD.

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In order to clarify the characteristics of the side effects of drugs in the elderly, we evaluated clinical features and liver function in 40 lymphocyte stimulation test (LST)-positive elderly. Their ages ranged from 64 to 90 years, with a mean age of 75 years. The major causative agents were antituberculosis agents, antibiotics and antiinflamatory agents, comprising 28%, 22% and 12% of whole drugs, respectively. Liver dysfunction, skin eruptions and fever were the major causes for carrying out LST. The mean latent period was 15 days, and in 80% of the cases, the side effect developed within four weeks after administration of the causative agent. Major clinical symptoms noted during the course were detected in more than the half of the cases. As for liver dysfunction, elevation of GOT, ALP and total bilirubin levels were noted in 76, 63 and 340 of the cases, respectively. These results showed that the hypersensitive side effects of the drugs could appear at any age even in the elderly, and clinical symptoms were often nonspecific and obscure. It was suggested that the presence of mild liver dysfunction and eosinophilia could be helpful markers for the early detection of drug-induced organ dysfunctions as well as careful observation. The possibility of the occurrence of the side effects must be considered on every drug administration. Presence of mild liver dysfunction and eosinophilia may be helpful markers for the early detection of drug-induced organ dysfunction.

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There has been some debate regarding abnormalities in visual evoked potentials (VEP) in Parkinson's disease (PD). To elucidate the mechanism causing abnormal VEP, we investigated the relationship between VEP and mental function in PD patients. Pattern reversal VEP was recorded in PD patients (n=27) and age-matched control subjects (n=14). PD patients consisted of two subgroups; PD without dementia (nD-PD; n=17) and PD with dementia (D-PD; n=10). Dementia was evaluated according to the criteria for dementia assigned in DSM III-R, and mental faculties were estimated by using the mini-mental state examination (MMSE). In pattern VEP recordings, P100 latency and amplitude were measured for each eye stimulated. No patient or control subject had impairment of corrected visual acuity or ophthalmological disease. There was no significant difference in age among the three groups (D-PD, nD-PD and control subjects). D-PD patients showed significantly prolonged P100 latency compared to nD-PD patients and control subjects (p<0.05). With respect to P100 amplitude, no significant difference was shown among the three groups. In PD patients, there was a rough correlation between P100 latency and MMSE score. No correlation was found between P100 amplitude and MMSE score. In control subjects, P100 latency did not correlate with advancing age. In PD patients, nD-PD patients showed a significant correlation between P100 latency and age, whereas D-PD patients presented no correlation. Abnormal VEP in PD has been mostly ascribed to dopaminergic deficiency in the retina. The present study, however, suggests that dysfunction in the central visual system plays a role in abnormal pattern VEP in PD, particularly in D-PD. Since patients with Alzheimer's disease have abnormal flash VEP but normal pattern VEP, VEP seems to be valid for differential diagnosis of dementing diseases.

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To elucidate the prognosis of elderly patients with asymptomatic aortic stenosis (AS) and to assess the timing of aortic valve replacement (AVR), 21 asymptomatic patients (8 men, 13 women, mean age: 75±8 years (54-89 years)), who had Doppler echocardiographic evidence of a significant aortic pressure gradient of greater than 40mmHg (mean gradient: 75±31mmHg), were followed for 33±10 months. During the follow-up, there were 4 cardiac events (2 cardiac deaths, 2 late AVRs), and 2 non-cardiac deaths (cerebro-vascular accidents). Among 15 survivors, 13 patients were in NYHA class I-II, and the remaining 2 patients were found to have malignant disease. Compared to the 17 patients without cardiac events, those with cardiac events had significantly larger CTR (58±6% vs. 53±3%; p<0.01), although there were no significant difference in electrocardiographic LVH, echocardiographic LV mass, and Doppler pressure gradient between the two groups. The prevalence of the development of cardiac symptoms during the follow-up was not high (12%) in patients without cardiac events. Among 4 patients with cardiac events, one patient who was 89 years-old at diagnosis died of heart failure, one patient had fatal myocardial infarction which seemed to be unrelated to AS, and two patients had successful late AVR because of new heart failure. The low incidence of fatal cardiac events in asymptomatic patients with aortic stenosis and the relatively high possibility of developing non-cardiac events in elderly patients indicate that the decision-making for AVR should not be solely based upon the pressure gradient detected by Doppler echocardiography. AVR can be held in reserve until the patients develop cardinal symptoms.

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The histological localization of S-100β protein in the hippocampus of human autopsy brains of 47 males (71-103 years old) and 90 females (56-104 years old) was studied immunohistochemically. Astrocytes and their processes were positively stained, but neuronal cells were not stained. However, Alzheimer's neurofibrillary tangle-like, senile plaque-like and fibrillary spindle figures were stained positively. S-100β positive structures increased in grade with age, but not always equally on Alzheimer's neurofibrillary tangles or senile plaques stained by Bodian method. Astrocytes decreased in number with age, and showed marked compensatory hypertrophy of their processes. S-100β positive structures seemed to be related to astroglial changes in terms of degeneration or loss of synapses.

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The clinical features of congestive heart failure in the elderly were investigated in 104 patients (57 males, 47 females, mean age of 79.2). Patients were divided into two subgroups, the readmission group, 33 patients who were readmitted within 6 months after discharge, and the non-readmission group. Chief complaints were dyspnea, edema, chest pain, loss of appetite, chest compression, and palpitation. Heart failure was caused by infection, myocardial ischemia, arrythmia, inappropriate drug usage including poor drug compliance, the use of beta-blockers, excessive intake of sodium, and anemia. Careful use of drug was essential especially in the readmission group. Major underlying heart disease were ischemic heart disease (39.4%), valvular disease (26.9%), hypertensive heart disease (9.6%), with cardio-myopathy, congenital heart disease seen in the minority. There was no statistically significant difference in underlying heart diseases between the two groups. Supraventricular arrhythmias such as atrial fibrillations, paroxysmal atrial fibrillations, paroxysmal supraventricular tachycardias, and premature atrial contractions were noted in 85.3% of the cases. Drugs for treatment were diuretics, digitalis, isosorbide dinitrate, calcium antagonists. ACE inhibitors and alpha-blockers were also used, showing that vasodilators were more extensively used than before. The major complications were hypertension (39.4%), renal dysfunction (27.9%), cerebrovascular disease (26.9%), diabetes mellitus (16.5%), arteriosclerosis obliterans (7.7%). Renal dysfunction, arteriosclerosis oblitrans was seen significantly more frequently in the readmission group. The prognosis at one year after admission was significantly worse in the readmission group. In summary, the major underlying diseases were ischemic heart disease, valvular disease, and hypertensive heart disease. Ischemic heart disease was seen more frequently than in previous investigations at our hospital. Education of patients and careful drug use are needed for prevention of readmission. The prognosis of the readmission group was significantly worse than of the non-readmission group.

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The administration of antihypertensive medications in the elderly (65 y.o. or more, 269 pts) was compared to that in younger cases (less than 65 y.o., 348 pts). All were outpatients who visited our clinic in 1990. The number of patients on a single therapeutic regimen was almost equal in both age groups. Once-a-day regimens were more common in the young (56.9% vs 48.3%, p<0.05), and three times-a-day regimens were more common in the elderly (14.7% vs 23.1%, p<0.01). The choice of antihypertensive drugs in patients with single therapy or combined therapy in the young was β blockers in 49.7%, Ca blockers in 39.4%, diuretics in 30.7% and ACE inhibitors in 17.8%, and those in the elderly were Ca blockers in 46.1%, diuretics in 44.2%, β blockers in 33.8%, and ACE inhibitors in 16.4%. The patients were subdivided into three groups according to the time of the initial visit to the clinic; initial visit during 1969-1979 (phase 1), 1980-1984 (phase 2) and 1985-1990 (phase 3). In the young, choice of β blockers and diuretics was most popular in phase 1. However, the choice of diuretics decreased in phase 2, and in phase 3 β blockers were used in 50.4%, Ca blockers in 43.2%, ACE inhibitors in 22.3% and diuretics in only 17.3%. In the elderly, diuretics were most popular followed by Ca blockers and β blockers in phase 1 and phase 2. In phase 3 Ca blockers were selected in 58.2% followed by both β blockers and ACE inhibitors in 28.4% then diuretics in 23.9%. These results indicate that the choice of antihypertensive drugs has, in brief, changed from β blockers or diuretics to β blockers or Ca blockers in the young and from diuretics or Ca blockers to Ca blockers in the elderly.

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Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS). The results showed that there were no mutations on these genes from 4 patients.

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