Recently, some Alzheimer-associated genes have been found: amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand conformation polymorphism and sequence analysis. These seven cases with FAD did not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes of FAD still remain to be not identified.
Many reports have established that apoE genotype distribution for the ε4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) α gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p<0.05). Polymorphisms of the ERα gene may be a genetic risk factor for SAD.
The apoE genotype is a genetic factor closely related SAD, but it is not full by appreciated how apoE has an effect on developing AD. There are few reports on the quantitative change of apoE, namely the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in the DS as well as AD was significantly higher than that in control group (p<0.05, p<0.05, respectively). High levels of apoE mRNA in AD and DS may play an important role in the development of Alzheimer pathology.

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With the numbers of elderly increasing rapidly, it is important for both individuals and society that the oldest old maintains autonomy. To know how to attain successful aging, we investigate the status of centenarians. The characteristics of centenarians in Tokyo is 1) low level of nutritional parameters, 2) low level of cholesterol and HDL-cholesterol, 3) low level of red blood cells and hemoglobin, 4) high level of CRP, 5) high level of homocysteine, 6) high level of von Willbrand factor. The incidence of dementia is 59.3%. Are these characteristics due to aging itself or other factors? We examined the effect of nutritional status, inflammation and level of homocysteine on the characteristics. The level of albumin is associated with serum level of lipid, RBC, ADL and cognitive function. The level of CRP is related to the level of albumin, suggesting that inflammation is related to nutritional status. The level of homocysteine is associated with the level of von Willbrand factor, suggesting that homocysteine is related to endothelial injury. From these data, we propose the hypothesis that proinflammatory status is associated with aging, resulting in a part of characteristics of centenarians. Homocysteine is partly responsible for endothelial injury. Intervention to suppress proinflammatory status and homocysteine level may promote QOL in the oldest old.

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[in Japanese]

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[in Japanese]

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Home care of patients is mainly performed by visiting nurses. To adequately perform the care, many type of knowledge are needed. Especially psychological approaches can minimize the pain to the patients and their family and shortening its duration and raising the efficacy of the treatment. Cooperation with clinical psychologists can be effective. We present three cases who were difficult to help by nurses alone Thus, Nurses provided in cooperation with the psychologists. First case was a 27-year-old man with cerebral palsy. Second case was a 55-year-old man with lung cancer, terminal stage. Third case was a 60-year-old man with amyotrophic lateral sclepsis. Through these different cases, we recognized the difficulties of medical care at home and also the importance of cooperation with psychologist. With the aging of society, the amount and type of home care needed will increase. Under long term insurance, the various type of knowledge, especially, psychological approaches is important. At the same time, training and education in this field for visiting nurses is required.

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Genetic background is an important factor for longevity. Life-style and environmental factors, such as nutrition, physical activity, smoking and alcohol, are also important. For example, obesity is negatively associated with health and longevity. It is known that dietary restriction is the most consistent method of extending life span in rats. In human, however, under nutrition as well as over nutrition is a risk factor for a short life. Losing weight is often dangerous in the elderly, in whom reserved physiological functions are limited. Smoking, diabetes mellitus and hypertension accelerate human aging, while physical activity and a moderate amount of alcohol is good to live long. Preventive medicine and health support are also important to promote longevity. Good results of new strategies such as custom-made health support and preventive treatment are anticipated in the near future. Accumulation of basic data in human aging and health are essential to the practice of preventive medicine and health support. A new comprehensive longitudinal study was started at the National Institute of Longevity Sciences (NILS) in 1997 (NILS-Longitudinal Study of Aging, NILS-LSA). The results of this study should be helpful for the practice of preventive medicine and health support.

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Hypercholesterolemia reduces production of nitric oxide (NO), a potent inhibitor of platelet aggregation, in endothelial cells. Recently platelet has been found to have NO synthase. Hypercholesterolemia may influence platelet NO production. We investigated NO-dependent inhibition of platelet aggregation in elderly hypercholesterolemic patients with total cholesterol (Tchol) of 240mg/dl or more (n=21). In elderly controls with Tchol less than 240mg/dl (n=61), L-arginine (5-50mM) inhibited ADP-induced platelet aggregation in a dose-dependent manner (42.4% inhibition at 50mM). However, L-arginine did not inhibit platelet aggregation in elderly hypercholesterolemic patients. L-arginine increased cyclic GMP production in elderly controls, but not in hypercholesterolemic patients (p<0.02). Hypercholesterolemic patients showed increased platelet aggregation compared with elderly controls (p=0.018). L-nitro-arginine methyl ester 12.5-50uM increased platelet aggregation in both groups. Superoxide dismutase improved L-arginine inhibition of platelet aggregation in elderly hypercholesterolemic patients (p=0.02). LDL cholesterol of 160mg/dl or more was an independent predictor for loss of L-arginine inhibition of platelet aggregation (relative risk 3.9, p=0.0098). This result suggests that hypercholesterolemia causes decreased NO-dependent inhibition of platelet aggregation due to reduced NO utilization. NO-dependent platelet aggregation may be a powerful tool for detection of vascular injury.

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Using a Minimum Data Set, we studied how the mental and physical conditions of elderly people with dementia changed during two years of institutionalization. Fifty-five patients with dementia of Alzheimer's type (DAT) and 25 with vascular dementia (VD) admitted to the dementia ward in Kyoto Higashiyama Geriatric Hospital were investigated. We assessed them at the time of their institutionalization, and every three months for two years. On institutionalization, a difference between DAT and VD was noted in the group in which more than 10 areas of Resident Assessment Protocols (RAPs) were triggered. The areas of delirium, communication, behavioral problem, activities, activities of daily living, dehydration/fluid maintenance, and psychotropic drugs were evenly triggered in both dementia groups. In the DAT group, however, mood state and dental care were also highly triggered while urinary incontinence, falls and nutritional status were highly triggered in the VD group.
Three months later, marked improvements were observed in all of the above areas. However, RAPs areas gradually increased subsequently, and there was marked difference in the areas and their course of progression between the dementia groups. In the DAT group, the trigger rate of the areas of communication, activities of daily living, urinary incontinence, dental care, nutritional status and falls gradually increased after 6 months of evaluation. However, the triggere rate in only three areas, such as communication, visual function and urinary incontinence, become higher, but their patterns of increase were irregular.
Mental and physical conditions of the patients with dementia were different in each dementia subtype on institutionalization, but these conditions improved soon after. However, the conditions were gradually became worse, and the pattern was different in each dementia group: DAT showed a slow and steady decline, but VD showed irregular progression and differed among individuals.

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We conducted a neuropsychological comparison between Parkinson's disease (PD; n=24) and healthy control subjects (n=12) using Rey's auditory-verbal learning test (RAVLT) and the Rey-Osterrieth complex figure test (RCFT) assessing memory function. In addition, to determine the function of cortical and subcortical areas, we measured the regional cerebral blood flow (rCBF) using N-isopropyl-p[¹²³I]-iodoamhetamine (¹²³I-IMP) and single photon emission computed tomography (SPECT) and analyzed the relationships between brain regions and memory function. On the RAVLT, significant group differences in recall words were found on all learning trials between patients with PD and control subjects, whereas recognition, learning rate and forgetting rate were basically the same. In addition, the primacy/recency effect was statistically equal for both groups. Results suggest faulty retrieval mechanisms in PD, whereas encoding and retention proceses did not prove to be affected. There were significant correlations between perfusion of the prefrontal and parietal cortices and total number of free recall in five trials. On the RCFT, recalls after 30 sec and 30min were impaired in patients with PD although no significant difference in accuracy scores obtained in copy was noted. A percent recall score calculated using the formula 100×[1-(copy-recall)/copy] was also decreased in patients with PD. There were significant correlations between perfusion of the occipital and parietal cortices and percent recall score. Our data suggest that auditory memory deficits based on the RAVLT in PD may be mainly related to frontal and parietal cortical dysfunction, while visual recall deficits based on the RCFT may be related to the parieto-occipital cortical dysfunction.

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The effects of music therapy on natural killer (NK) cell count and activity (NKCA) were studied in 19 persons. Alzheimer's disease, cerebrovessel disease and Parkinson's disease subjects were assigned to a music therapy. Blood samples were drawn at rest and after completion of music therapy.
Music therapy did not change the number of circulating lymphocytes. The percentage of NK cells increased during music therapy, along with an increase in the NK cell activity. The proportion of T cells, CD4 and CD8 did not change significantly during music therapy. One hour after the music therapy session, plasma adrenaline increased but cortisol and noradrenalin did not change.
The results indicate that music therapy can significantly increase NK cell count and activity. The change in NK cell and function were independent of neuro-degenerative diseases.

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To clarify the influence of acupuncture therapy on the quality of life (QOL) of the elderly, the acupuncture and moxibustion were performed on 35 elderly subjects (8 men and 27 women) with a mean age 79.1 living in nursing homes and elderly care houses. The acu-points were chosen according to their symptoms. Changes in pain and other complaints, body condition, appetite, sleep, bowel movement and activity of daily living (ADL) were evaluated by questionnaires. A total of 38 symptoms were reported.
A high rate of improvement was seen in pain and stiffness. For example, there was 86% improvement in low back pain, 84% in knee joint pain and 82% in shoulder stiffness. Concerning body conditions, decrease of fatigue, relaxed of feeling, improvement in appetite, sleep and bowel movement were observed. Furthermore, gait and ADL were also improved.
These results suggested that acupuncture and moxibustion are useful to improve QOL in the elderly.

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We examined the way medical students think about end-of-life care in the elderly by a questionnaire survey. The major variables of the evaluation instrument included the students'idea of the special nature of end-of-life care for the elderly, the necessity for disclosure of the name of disease, consideration for patient's age on disclosure, advance directives concerning their life-sustaining treatment, and communication concerning preferences for end-of-life care. The final items on the instrument asked for student comments about end-of-life care in the elderly. We analyzed this qualitative data using the process of immersion/crystallization. We received 95 responses, and of these 65 (68%) provided written commentaries that were analyzed using qualitative techniques. Fifty-nine (62%) students pointed out the special nature of end-of-life care in the elderly and most of them (96%) needed the disclosure of the name of disease. Fifty-two (55%) students agreed with advance directives for end-of-life care and 88 (93%) students pointed out the importance of communication with regard to patients' preferences. Medical students' concerns about end-of-life care in the elderly related to three major domains: 1) patient-physician relationship; 2) the procedures of end-of-life care; and 3) emotional and intuitive comments. These results suggest that in the education of geriatric medicine the patient-physician's relationship about end-of-life care is important and we may need to introduce systematic lectures and practical training.

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We report three elderly patients with hyperostosis cranii (HC). Patient 1 had two episodes of unconsciousness; patient 2, headache; and patient 3, dementia. On the basis of the classification of Moore using skull films, patients 1 and 2 showed hyperostosis frontoparietalis and patient 3 had hyperostosis frontalis interna. Electroencephalography showed transient generalized spike and slow wave complexes over the frontal lobes in patient 1. Magnetic resonance (MR) images showed frontal lobes compressed by the thickness of the frontal bones in all patients and thickened parietal bones in patients 1 and 2.
Because findings in our series and in the literature suggest that HC may show unexpected neuropsychiatric symptoms, HC should be checked in elderly patients whose presenting symptoms include epilepsy, dementia, psychiatric disease, headache and so on. MR images should reveal the relationship between clinical symptoms and the deformation of brains by the skull.

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An 88 year-old woman was admitted complaining of headache. CT scan of the head revealed a right subdural hematoma. She had been followed by a local physician because of chronic thrombocytopenia. Her peripheral platelet count on admission was 0.5×10⁴/μl, with a high serum level of PAIgG. Bone marrow examination revealed marked increase of megakaryocyte. Idiopathic thrombocytopenic purpura (ITP) accompanied with chronic subdural hematoma was diagnosed. Transient increase of platelet count and improvement of subdural hematoma was obtained by administration of prednisolone. However, platelet count decreased with tapering of prednisolone. Then combined administration of a Chinese herbal medicine, EK-49, and ascorbic acid was started. Platelet count gradually increased and no adverse effects were experienced. These results indicated that elderly patients with chronic subdural hematoma can be treated non-invasively, and that a combination of EK-49 and ascorbic acid may be effective in the treatment of refractory ITP.

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Two elderly patients with sarcoidosis complicated with Sjögren's syndrome are described.
Case 1: A 70-year-old woman was admitted due to dry eyes. Histological examination of a minor salivary gland specimen revealed lymphocytic infiltration, which was compatible with Sjögren's syndrome. Because uveitis was demonstrated, transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung sarcoidosis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis.
Case 2: A 70-year-old woman was admitted due to dyspnea on exercise and blurred vision. Two years previously, Sjö gren's syndrome was diagnosed because of a positive Shirmer test and positive SS-A antibody. Result of ophthalmic examination were compatible with uveitis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis.
Certain similarities between sarcoidosis and Sjögren's syndrome in terms of immunological aspects have attracted attenion. In the present manuscript, a possible relationship between the two diseases as well as the characteristics of elderly sarcoidosis are discussed.

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A 61-year-old man with recurrent ischemic attacks was examined by diffusion-weighted MRI (DWI). He had reversible right hemiparesis and dysarthria five times during admission. DWI was obtained on the first two attacks, the last attack and four days after the last attack. The first two attacks were clinically diagnosed as transient ischemic attack (TIA), and the last attack was cerebral infarction with symptoms persistent for one week with Babinski's sign. In the first and last images the apparent diffusion coefficient (ADC) declined to approximately 80% of the corresponding area. We conclude that different images showed TIA with ADC declining, TIA without ADC declining, the hyperacute phase of cerebral infarction before ADC declining, and cerebral infarction after ADC declining. Consecutive DWIs were helpful to understand the character of recuurent ischemic attacks.

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