Hidetoshi Endo

Plasma cortisol levels in elderly female subjects with Alzheimer’s disease: a cross-sectional and longitudinal study

We investigated the plasma cortisol levels at a fasting state in elderly female Alzheimers disease (AD), vascular dementia (VD), and non-demented subjects (n=66, 28 and 21, respectively). Twenty-eight AD subjects were followed for 40 months. The plasma cortisol levels in AD and VD subjects were significantly higher than those of non-demented subjects at baseline. In AD subjects in relatively early stages of the disease [Mini-Mental State Examination (MMSE)], at baseline, high plasma cortisol led to rapid declines in MMSE scores over a 40-month period.

A Comparison of Depressive Mood of Older Adults in a Community, Nursing Homes, and a Geriatric Hospital: Factor Analysis of Geriatric Depression Scale

The Geriatric Depression Scale (GDS)-15 was used in 607 adults aged 65+ years living in a community, nursing homes, and a general hospital to explore characteristics of depressive mood in different care settings. Factor analysis of GDS-15 extracted 4 factors labeled unhappiness, apathy and anxiety, loss of hope and morale, and energy loss. The scale scores labeled unhappiness, apathy and anxiety, and loss of hope and morale were negatively correlated with the Barthel Index and the Mini-Mental State Examination scores. The results classified the depressive patterns into 2 types, one fitting the nursing home residents and the other fitting the hospital patients. The dominant factors of the nursing-home type were unhappiness and loss of hope and morale, and the hospital type was highly related with apathy and anxiety. The results indicate an extended utility of the GDS-15 for a deeper understanding of depressive mood in various care settings.

Cytoskeletal Neurofilament Gene Expression in Brain Tissue from Alzheimer's Disease Patients. I. Decrease in NF-L and NF-M Message

The cytoskeletal changes seen in brains of patients with Alzheimers disease include neurofibrillary tangles, neuritic plaques, Hirano bodies, and granulovacuolar degeneration. Northern and slot blot analyses were used to investigate the expression of the genes coding for actin, tubulin, neurofilaments, and histone in brain tissue from Alzheimers disease patients and normal aged controls. We found a marked decrease of 94% in the expression of the neurofilament gene coding for the medium size subunit (150 kDa) and a 73% decrease in the expression of the gene coding for the small subunit (68 kDa) in Alzheimers disease patients as compared to controls. Expression of the other genes, such as actin and histone, did not show any significant difference. Expression of the gene coding for medium size, neurofilament gene was not decreased in other neurodegenerative diseases, such as amyotrophic lateral sclerosis and Parkinsons disease. This abnormality in neurofilament gene expression may explain some of the pathologic features found in Alzheimers disease patients.

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

Estriol retards and stabilizes atherosclerosis through an NO-mediated system

Estriol (E3) has little effect on the female genitals. E3 is used in hormone replacement therapy, particularly in Europe and Japan, since it obviates the need for progestin administration. However, the effect of E3 on atherosclerosis has not been elucidated. In this study, we evaluated the effect of E3 on the progression of atherosclerosis in a rabbit model. Thirty-six rabbits total were used. Twenty-eight were bilaterally oophorectomized, and 8 were not. The rabbits were divided into 5 groups and treated for 12 weeks as follows. Gp I (n = 8) was fed a high cholesterol diet (HCD; standard diet plus 0.5% cholesterol); Gp II (n = 8) was fed a HCD with E3 (0.3 mg/kg/day); Gp III (n = 8) was fed a HCD with 17beta estradiol (E2) (0.1 mg/kg/day); Gp IV (n = 8), the non oophorectomized group, was fed a HCD; and Gp NC was oophorectomized (n = 4), and fed a regular diet. E3 treatment increased the plasma E2 and E3 levels in Gp II. The plasma lipid levels were not altered by the E2 or E3 treatment. A HCD diminished the acetylcholine-induced NO mediated relaxation in the thoracic aorta. The E2 treatment (Gp III) and E3 treatment (Gp II) restored the aortic basal NO release and the aortic cyclic GMP levels, particularly effectively in the E3 group. E3 treatment also decreased the atherosclerotic area, and its effect was comparable with E2 (surface involvement: 41.2 +/- 5.1% in Gp I; 10.1 +/- 2.7% in Gp II; and 6.5 +/- 1.3% in Gp III). All four hyperlipidemic groups showed an increase of eNOS mRNA in the aortae, and this was especially pronounced in Gps II and III. The level of peroxynitrite, as determined by immunohistochemical nitrotyrosine staining, was lower in Gps II and III than in Gp I. E3 strongly activates NO-mediated systems, and could play a role in retarding the progression of atherosclerosis and in stabilizing atheroma.

Factors associated with carotid atherosclerosis in community‐dwelling oldest elderly aged over 80 years

Background:  Hypertension, hyperlipidemia, impaired glucose tolerance and smoking have been known to be risk factors for atherosclerosis. Recently, it was shown that hyperhomocysteinemia is also a risk factor for cerebral vascular disease and atherosclerosis. However, it is unknown if these are also risk factors in the oldest elderly population aged 80 years or older. We carried out a cross‐sectional analysis to determine the associated factors with carotid atherosclerosis in the oldest elderly living in the community.

Association of lower hemoglobin level with depressive mood in elderly women at high risk of requiring care

Aim:  Despite the high prevalence of anemia and depression in the elderly, there have been few studies exploring the association between these two conditions. In the current study, we analyzed the association of hemoglobin level and depressive mood in a group of community‐dwelling elderly at high risk of requiring care.

Attitudes toward disclosing the diagnosis of dementia in Japan.

BACKGROUND The rapid increase in the elderly population in Japan has triggered a debate on whether or not patients with dementia should be informed of their diagnosis. The purpose of the present study was to investigate the attitudes of people in a large city in Japan toward the disclosure of a diagnosis of dementia. METHODS In Study 1, 2000 residents aged 40-64 and 5000 residents aged 65 and over were sampled randomly, and a structured questionnaire was sent to them by mail. In Study 2, we administered a structured interview-based questionnaire to 3949 randomly enrolled residents of Nagoya City aged 45 and over whose family member had been certified as needing long-term care. RESULTS In Study 1, 79.8% of the younger respondents (n = 710) stated that they would prefer the disclosure of a hypothetical diagnosis of dementia, as did 75.5% of the older respondents (n = 2162). Furthermore, 85.1% (n = 749) of the younger respondents and 82.5% (n = 2181) of the older respondents stated that they would prefer that the patient be told his or her hypothetical diagnosis of dementia. In Study 2, in the case of care recipients without dementia, 68.3% (n = 650) of their family members preferred disclosure of a hypothetical diagnosis of dementia. Among the families of care recipients who had dementia, 58.4% (n = 301) of family members preferred disclosure. CONCLUSIONS The present survey of caregivers and non-caregivers in an urban city of Japan demonstrated that the desire for disclosure of a diagnosis of dementia is relatively high.

HLA system in senile dementia of Alzheimer type and multi-infarct dementia in Japan

To clarify the genetic factors in demented patients in Japan, HLA antigens were examined by the authors. They found a significant association between HLA B16 and senile dementia of Alzheimer type. Also a significant difference was observed in the occurrence of HLA Cw 3 between patients with dementia and controls. In the general population the frequency of B16 is higher in Europe and the USA than it is in Japan. So the authors suppose that the difference in the prevalence of senile dementia of Alzheimer type between Japan and other countries is caused by genetic factors.

Burden reduction of caregivers for users of care services provided by the public long-term care insurance system in Japan

We surveyed the care burden of family caregivers, their satisfaction with the services, and whether their care burden was reduced by the introduction of the LTCI care services. We randomly enrolled 3000 of 43,250 residents of Nagoya City aged 65 and over who had been certified as requiring long-term care and who used at least one type of service provided by the public LTCI; 1835 (61.2%) subjects returned the survey. A total of 1015 subjects for whom complete sets of data were available were employed for statistical analysis. Analysis of variance for the continuous variables and χ(2) analysis for that categorical variance were performed. Multiple logistic analysis was performed with the factors with p values of <0.2 in the χ(2) analysis of burden reduction. A total of 68.8% of the caregivers indicated that the care burden was reduced by the introduction of the LTCI care services, and 86.8% of the caregivers were satisfied with the LTCI care services. A lower age of caregivers, a more advanced need classification level, and more satisfaction with the services were independently associated with a reduction of the care burden. In Japanese LTCI, the overall satisfaction of the caregivers appears to be relatively high and is associated with the reduction of the care burden.