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Biomedical subjects

Hiroyuki Umegaki

Publications and source records attributed to Hiroyuki Umegaki.

At least 19 recordsLinked to original sources
PubMed2006

Functional recovery of the striatal cholinergic system in aged rats by adenoviral vector-mediated gene transfer of dopamine D2 receptor.

We previously reported that the striatal dopamine-acetylcholine (ACh) interaction was affected by the aging process, possibly via a decrease of the striatal D(2)R expression. In the current study, the ACh responses to the infusion of 0.1microM of the D(2)R agonist quinpirole were measured with microdialysis techniques after adenoviral vector-mediated gene transfer of D(2)R into the striatum of 25-month-old rats. The D(2)R gene-transferred rats showed significantly stronger responses of the striatal cholinergic neurons to the infusion of the D(2)R agonist than did control vector-transferred rats. The current study suggests that age-associated functional decline with decreased gene expression of the receptor may be restored by intervention.

Acetylcholine↗
PubMed2006

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.

Adult↗
PubMed2006

Which two questions of Mini-Mental State Examination (MMSE) should we start from?

The MMSE is a simple and commonly used instrument to evaluate cognitive impairment. With the aim of enabling the examiner to skip a large portion of the MMSE when screening subjects with lower possibility of cognitive impairment, we examined the internal distribution of the MMSE scores among 792 older adults visiting a teaching hospital, a long-term care hospital, nursing homes, and a geriatric clinic. The correlation coefficients between the summed scores of any two items of MMSE and the total score were compared. A receiver operating characteristic (ROC) curve was drawn to show the sensitivity and the specificity of predicting cognitive impairment, which was defined by the total MMSE score being less than 24. The mean MMSE score was 20.5 +/- 6.9 (+/-S.D.). A good predictor for cognitive impairment was the summed scores of the time orientation and serial sevens with a sensitivity of 98.2% and a specificity of 69.2% if cut-off was set at 7/7+. This finding appears to help streamline the screening process for cognitive impairment in general elderly population.

Aged↗
PubMed2006

Depletion of cholinergic neurons in the nucleus of the medial septum and the vertical limb of the diagonal band in dementia with Lewy bodies.

The cholinergic basal forebrain is divided into four subregions (Ch1-4), and cholinergic neuronal loss in the nucleus basalis of Meynert (Ch4) has been correlated with cognitive impairments in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). However, the Ch1-2 regions, which provide the major cholinergic innervation to the hippocampus, have not been investigated in DLB. The purpose of this study was to reveal the cholinergic neuronal changes in the medial septum (Ch1) and the nucleus of the vertical limb of the diagonal band (Ch2) of DLB brains. Using choline acetyltransferase (ChAT) immunohistochemistry, we showed that the number of ChAT-immunoreactive neurons in DLB brains was significantly lower than the numbers in AD and non-demented (control) brains. No significant difference in the number of ChAT-immunoreactive neurons was found between the AD and control brains. Moreover, the size of the ChAT-immunoreactive neurons was significantly smaller in the AD and DLB brains than in the control brains. These results show that cholinergic neurons of the Ch1-2 regions are more severely affected in DLB than in AD. Our DLB cases did not fulfill the neuropathologic criteria for definite AD. Furthermore, some Lewy bodies were observed in the Ch1-2 regions. Thus, cholinergic neuronal loss in the Ch1-2 regions might be specific to the pathology of DLB. Taking the distribution of cholinergic fibers in the hippocampus into consideration, this study suggests a possibility that hippocampal cholinergic projection is involved in Lewy-related neurites in the CA2-3 regions, the origin of which remains unclear.

Aged↗
PubMed2006

Behavioral, psychological and physical symptoms in group homes for older adults with dementia.

BACKGROUND: Despite the recent dissemination of group homes in Japan for older adults with dementia, the behavioral and psychological features of the residents remain unknown. To clarify the association of such features with the levels of difficulty encountered by caregivers in coping with these symptoms, we have conducted a survey to compare the frequencies of the symptoms among group homes, nursing homes and a long-term care hospital. METHODS: Five hundred and eighty-six older adults aged 65 years or more were sampled. Data were consecutively collected from questionnaires given to the caregivers. The questionnaire included basic activities of daily living, the Mini-mental State Examination, frequencies of behavioral, psychological and physical symptoms, and the levels of difficulty in coping with the symptoms. RESULTS: In group homes, requests to go home, urinary incontinence and frequent complaining were the most commonly observed symptoms. The symptoms associated with disorientation, anxiety and depression were frequently observed in all three care settings. Most of the symptoms were more frequently observed in group homes than in the other two care settings. However, the levels of difficulty in coping with most of the symptoms were the highest in the long-term care hospital, followed in order by the group homes and nursing homes. In group homes, inappropriate sexual behavior was the symptom creating the most stress for the caregivers, followed by verbal and nonverbal abuse and changeable mood. CONCLUSIONS: The symptomatic traits of residents in group homes were clarified in the present study. These findings could be helpful in considering desirable placement or the improvement of eligible service provision for older adults with dementia in care facilities.

Aged↗
PubMed2006

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.

Activities of Daily Living↗
PubMed2006

[Target of glycemic control of elderly diabetes mellitus patients].

Although the number of older diabetes mellitus patients is growing rapidly all over the world including Japan, there has been little evidence regarding the target of plasma glucose levels in elderly diabetes mellitus patients. Older persons with diabetes mellitus have higher rates of functional disability and coexisting illness. Plasma glucose levels should be controlled properly in elderly, however, the levels must be determined individually considering their complications. Because the risks of hypoglycemia, and/or drug-drug interactions are higher in the older patients, the medical providers must balance benefits and risks for every patient. RCT in older diabetes mellitus patients would be required.

Aged↗
PubMed2006

Stimulation of the hippocampal glutamate receptor systems induces stress-like responses.

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis controls glucocorticoid secretion and is in turn controlled by a diverse set of afferents in the brain. However, the precise mechanisms underlying these actions remain to be elucidated. In our previous study, a lesion in the entorhinal cortex, which is the major provider of glutamatergic innervation to the hippocampus, significantly attenuated the elevation of adrenocorticotropic hormone (ACTH) in plasma during immobilization stress. In the present study, we examined the effects of microinjections of glutamatergic agonists into the hippocampus on plasma ACTH and glucose concentrations. We also studied the interactions between glutamate and acetylcholine in this response in the hippocampus. MATERIALS AND METHODS: NMDA and AMPA subtypes of glutamate agonists were microinjected into the rat hippocampus, and ACTH and glucose levels in plasma were measured. The interaction between cholinergic and glutamatergic systems was investigated pharmacologically. RESULTS: Both the NMDA and AMPA subtypes of glutamate agonists induced elevations of plasma ACTH and glucose levels in a dose-dependent fashion. These responses were independent of those induced by activation of the hippocampal cholinergic system. CONCLUSION: Stimulation by the NMDA and AMPA subtypes of glutamate receptors in the hippocampus induced elevations of plasma ACTH and glucose, and these responses were independent of the cholinergic system.

Acetylcholine↗
PubMed2005

Dopamine D2 receptor plays a role in memory function: implications of dopamine-acetylcholine interaction in the ventral hippocampus.

RATIONALE: The role of the hippocampal dopaminergic system in mnemonic function has not been clarified yet. OBJECTIVE: We previously reported that the dopamine D2 receptor (D2R) is involved in the regulation of acethylcholin (ACh) release in the hippocampus. In this study, we further investigated ACh-dopamine (DA) interaction in the hippocampus and its involvement in mnemonic function. METHODS: For experiment 1, rats fed with Cholin (Ch)-deficient chow were used. We examined the effects of D2R antagonist, raclopride, on cognitive performance using a passive avoidance task. We further carried out in vivo microdialysis to assess the effect of infusion of D2R agonist, quinpirole, into the ventral hippocampus on its capacity to release ACh. For experiment 2, rats fed with normal chow were used. The performance of a radial arm maze task was assessed to examine the effects of hippocampal injection of D2R agonist, quinpirole, on memory impairment induced by scopolamine, a muscarinic ACh antagonist. RESULTS: In experiment 1, rats fed with Ch-deficient chow showed impaired performances indicated by prolonged latency on retention trials of a passive avoidance task following the hippocampal injection of D2R antagonist, and showed reduced capacity to release ACh following the injection of D2R agonist compared with rats fed with normal chow. In experiment 2, memory impairment induced by the intraperitoneal injection of scopolamine was ameliorated by the injection of D2R agonist into the ventral hippocampus. CONCLUSION: These results indicate the possible involvement of hippocampal ACh-DA interaction in mnemonic processing.

Acetylcholine↗
PubMed2005

Influence of behavioral and psychological symptoms of dementia (BPSD) and environment of care on caregivers' burden.

With increasing population of older adults in need of care, caregiver's burden is becoming a major concern. We investigated the relative contributions of BPSD of care recipients, caregiver's background and the care environment to caregiver's burden assessed by using Zarit burden interview (ZBI). Among BPSD, inability of finding the way home, inability of managing money and fecal incontinence were the most difficult symptoms to cope with. A path analysis, by which we constructed a network model to clarify the contributions of the factors examined to the caregiver's burden, indicated that the severity of dementia, the feeling of "would rather die than be in the same condition" and the physical pain of the caregivers showed great direct influences on the score of the ZBI. In conclusion, we clarified kinetic and dynamic interactions of factors affecting caregiver's burden by using a path analysis. The model indicates that the caregiver's burden can be affected not merely by the illness of the care recipients but by the caregiver's background and the care environment.

Activities of Daily Living↗
PubMed2005

Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking.

Dopamine (DA) signals are transmitted via specific receptors including the D2 receptors (D2R). Previous studies have shown that D2R upregulation in the nucleus accumbens (NAc) attenuated alcohol consumption. We hypothesized that upregulation of D2R in the NAc would significantly influence alcohol drinking. We tested this hypothesis by determining the effect that D2R upregulation has on alcohol intake in genetically altered mice lacking D2Rs. After a steady baseline of drinking behavior was established for all mice, a null vector or a genetically modified adenoviral vector containing the rat D2R cDNA was infused into the NAc of wild-type (Drd2+/+), heterozygous (Drd2+/-), and receptor-deficient mice (Drd2-/-). Ethanol intake and preference were then determined using the two-bottle choice paradigm. Our results indicated that Drd2+/+ mice treated with the D2R vector significantly attenuated (58 %) their ethanol intake as well as reduced preference. Drd2+/- and mutant mice showed a similar attenuation, although the change was not as marked (12 %) and did not last as long. In contrast, Drd2-/- mice treated with the D2R vector displayed a temporary but significant increase (46 %) in ethanol intake and preference (consumption). These results supported the notion that the D2R plays an important role in alcohol consumption in mice and suggest that a key threshold range of D2R levels is associated with elevated alcohol consumption. Significant deviations in D2R levels from this range could impact alcohol consumption, and could help to explain possible individual variations in alcohol response, metabolism, sensitivity and consumption.

Alcohol Drinking↗
PubMed2005

[Awareness of dementia in older adults attending dementia-prevention programs in community healthcare centers].

Recently, the dementia-prevention program hosted by the Ministry of Health, Welfare and Labor has been widely implemented. We administered a questionnaire to 347 elderly adults (mean age: 71, mean MMSE score: 27.2) who attended programs in community healthcare centers. The questionnaire consisted of questions concerning: (1) belongings (2) knowledge about dementia (3) opinions about revealing the diagnosis of dementia to patients (4) anxiety for own onset of dementia. Regarding the knowledge about dementia, 17% of the participants knew about drug therapy, and 13% of them knew about legal guardianship. The results indicated a limited knowledge about facilities where demented people can be placed (home: 39%, hospital: 43%, nursing home: 62%, group-home: 25%). As for revealing the diagnosis, 68% of the participants hoped they would be informed of the diagnosis if they become demented, while 66% of them felt anxiety about having dementia in the future. In terms of difference by age (> or = 70 v.s. < or = 69), while the older group had low knowledge about the facilities and felt more anxiety about their own onset of dementia (chi2 test p < 0.05, Mann-Whitney U test p < 0.05), there were no intergroup difference regarding their expectations of being told about the diagnosis of dementia. Overall, the results of the questionnaire suggest that appropriate education of dementia to older adults may contribute to early diagnosis of the community level, thereby may maximize the effect of therapeutic interventions.

Aged↗
PubMed2005

The entorhinal cortex regulates blood glucose level in response to microinjection of neostigmine into the hippocampus.

OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus elicited stress-like responses reflected by the release of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. The current study was designed to examine the role of the entorhinal cortex in regulation of blood glucose elevation induced by hippocampal neostigmine injection. MATERIAL AND METHODS: We produced the entorhinal cortex lesions in 9 week-old male Wistar rats by the bilateral injections of the cell-selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected into the rat hippocampus in a volume of 1microl for 1min using a CMA/100 microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma glucose concentrations were determined by the immobilized enzyme membrane/H2O2 method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo, Japan). RESULTS: Compared with sham-operated control rats, the entorhinal lesions produced by ibotenic acid significantly attenuated the elevations of blood glucose evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of plasma ACTH in response to the injection was observed between the entorhinal-lesioned rats and controls. CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a role in the central nervous systems regulation of blood glucose and may be involved in a stress response presumably via an alternative pathway.

Animals↗
PubMed2004

The clock drawing test as a valid screening method for mild cognitive impairment.

To validate the Clock Drawing Test (CDT) as a screening method for detecting mild cognitive impairment (MCI) and to find the appropriate scoring protocol and its cutoff point, we compared the sensitivity and specificity of three CDT protocols. Subjects included 219 outpatients with memory complaints, who were attending the geriatric memory clinic. Cahn's protocol, with a cutoff point of 7, was more successful at differentiating clinically diagnosed MCI subjects from normal elderly individuals, with higher sensitivity (74.7%) and specificity (75.6%), than were the other protocols. The CDT, as a handy screening method, may be useful for clinicians to reliably identify subjects with MCI, and it may contribute to early detection of dementia.

Aged↗
PubMed2004

DRD2 gene transfer into the nucleus accumbens core of the alcohol preferring and nonpreferring rats attenuates alcohol drinking.

BACKGROUND: Transient overexpression of the dopamine D2 receptor (DRD2) gene in the nucleus accumbens (NAc) using an adenoviral vector has been associated with a significant decrease in alcohol intake in Sprague Dawley rats. This overexpression of DRD2 reduced alcohol consumption in a two-bottle-choice paradigm and supported the view that high levels of DRD2 may be protective against alcohol abuse. METHODS: Using a limited access (1 hr) two-bottle-choice (water versus 10% ethanol) drinking paradigm, we examined the effects of the DRD2 vector in alcohol intake in the genetically inbred alcohol-preferring (P) and -nonpreferring (NP) rats. In addition, micro-positron emission tomography imaging was used at the completion of the study to assess in vivo the chronic (7 weeks) effects of ethanol exposure on DRD2 levels between the two groups. RESULTS: P rats that were treated with the DRD2 vector (in the NAc) significantly attenuated their alcohol preference (37% decrease) and intake (48% decrease), and these measures returned to pretreatment levels by day 20. A similar pattern of behavior (attenuation of ethanol drinking) was observed in NP rats. Analysis of the [C]raclopride micro-positron emission tomography data after chronic (7 weeks) exposure to ethanol revealed clear DRD2 binding differences between the P and NP rats. P rats showed 16% lower [C]raclopride specific binding in striatum than the NP rats. CONCLUSIONS: These findings further support our hypothesis that high levels of DRD2 are causally associated with a reduction in alcohol consumption and may serve as a protective factor against alcoholism. That this effect was seen in P rats, which are predisposed to alcohol intake, suggests that they are protective even in those who are genetically predisposed to high alcohol intake. It is noteworthy that increasing DRD2 significantly decreased alcohol intake but did not abolish it, suggesting that high DRD2 levels may specifically interfere with the administration of large quantities of alcohol. The significantly higher DRD2 concentration in NP than P rats after 7 weeks of ethanol therefore could account for low alcohol intake.

Alcohol Drinking↗