Publications by authors named "Katsuyoshi Mizukami"

85 Publications

Factors Associated with Volunteer Activities and Sleep Efficiency in Older Adults with Hypertension: A Sequential Model Study.

Geriatrics (Basel) 2021 Sep 11;6(3). Epub 2021 Sep 11.

Graduate School of Comprehensive Human Sciences, Department of Human Care Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.

The purpose of this study was to examine, using a sequential model, factors associated with volunteer participation and sleep efficiency in Japanese older adults receiving treatment for hypertensive disease. A questionnaire survey was conducted to collect data on participant demographics, lifestyle, health status, and depression, and sleep activity monitors were used to objectively measure sleep status and sleep efficacy. Of the 167 respondents, the 59 being treated for hypertension were divided into two groups based on their participation in volunteering. Comparison between the groups showed significant differences in nocturnal awakening, sleep efficiency, and nap frequency. Volunteers had less nocturnal awakening, increased sleep efficiency, fewer naps, and decreased depression. Covariance structure analysis of the survey data and sleep measurements for hypertensive older adults in the volunteer group was performed by modeling the relationships between variables with a path diagram. Our model showed strong goodness of fit (χ test = 15.636, = 0.111, GFI = 0.925, AGFI = 0.842, CFI = 0.925, RMSEA = 0.099). The findings of this study suggest that older adults with hypertension who participate in volunteer activities have less nocturnal awakening, improved sleep quality, and reduced risk of depression, and provides evidence to promote social participation in volunteering among older adults with hypertension.
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http://dx.doi.org/10.3390/geriatrics6030089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482086PMC
September 2021

Factors Associated with Volunteer Activities and Sleep Efficiency in Older Adults with Hypertension: A Sequential Model Study.

Geriatrics (Basel) 2021 Sep 11;6(3). Epub 2021 Sep 11.

Graduate School of Comprehensive Human Sciences, Department of Human Care Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.

The purpose of this study was to examine, using a sequential model, factors associated with volunteer participation and sleep efficiency in Japanese older adults receiving treatment for hypertensive disease. A questionnaire survey was conducted to collect data on participant demographics, lifestyle, health status, and depression, and sleep activity monitors were used to objectively measure sleep status and sleep efficacy. Of the 167 respondents, the 59 being treated for hypertension were divided into two groups based on their participation in volunteering. Comparison between the groups showed significant differences in nocturnal awakening, sleep efficiency, and nap frequency. Volunteers had less nocturnal awakening, increased sleep efficiency, fewer naps, and decreased depression. Covariance structure analysis of the survey data and sleep measurements for hypertensive older adults in the volunteer group was performed by modeling the relationships between variables with a path diagram. Our model showed strong goodness of fit (χ test = 15.636, = 0.111, GFI = 0.925, AGFI = 0.842, CFI = 0.925, RMSEA = 0.099). The findings of this study suggest that older adults with hypertension who participate in volunteer activities have less nocturnal awakening, improved sleep quality, and reduced risk of depression, and provides evidence to promote social participation in volunteering among older adults with hypertension.
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http://dx.doi.org/10.3390/geriatrics6030089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482086PMC
September 2021

A cross-sectional study of foot-ground clearance in healthy community dwelling Japanese cohorts aged 50, 60 and 70 years.

BMC Geriatr 2021 03 6;21(1):166. Epub 2021 Mar 6.

Institute for Health and Sport (IHeS), Victoria University, P.O. Box 14428, VIC, 8001, Melbourne, Australia.

Background: Falls-related injuries are particularly serious for older people, causing pain, reduced community engagement and associated medical costs. Tripping is the leading cause of falls and the current study examined whether minimum ground clearance (MFC) of the swing foot, indicating high tripping risk, would be differentiated across cohorts of healthy 50-, 60- and 70-years old community residents in Japan.

Methods: A cross-sectional population comprising the three groups (50s, 60s and 70s) of 123 Konosu City residents consented to be recorded when walking on an unobstructed surface at preferred speed. Gait biomechanics was measured using high speed (100 Hz) motion capture (OptiTrack - Natural Point Inc.), including step length and width, double support, foot contact angle and MFC (swing toe height above the ground). Multivariate Analysis of Variance (MANOVA) was used to confirm ageing effects on MFC and fundamental gait parameters. Pearson's correlations were performed to identify the relationships between mean MFC and other MFC characteristics (SD and SI), step length, step width, double support time and foot contact angle.

Results: Compared to 50s, lower step length was seen (2.69 cm and 6.15 cm) for 60s and 70s, respectively. No other statistical effects were identified for spatio-temporal parameters between the three groups. The 50s cohort MFC was also significantly higher than 60s and 70s, while step-to-step MFC variability was greater in the 70s than 50s and 60s. Pearson's correlations demonstrated that more symmetrical gait patterns were associated with greater MFC height, as reflected in greater symmetry in step width (50s), MFC (60s) and foot contact angle (70s). In the 70s increased MFC height correlated with higher MFC variability and reduced foot contact angle.

Conclusions: MFC height reduces from 60 years but more variable MFC appears later, from 70 years. While symmetrical gait was accompanied by increased MFC height, in the 70s group attempts to increase MFC height may have caused more MFC variability and lower foot contact angles, compromising foot-ground clearance. Assessments of swing foot mechanics may be a useful component of community falls prevention.
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http://dx.doi.org/10.1186/s12877-021-02117-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937319PMC
March 2021

[The effect of whole body vibration by sonic waves on mood, the autonomic nervous system, and brain function in elderly].

Nihon Ronen Igakkai Zasshi 2020 ;57(4):441-449

Graduate School of Comprehensive Human Science, Department of Social Health and Stress Management, University of Tsukuba.

Aim: The purpose of this study was to clarify the effect of sonic wave vibration (SWV) on mood, the autonomic-nervous system, brain function and cognitive function in elderly people.

Methods: We randomly assigned 24 late-stage elderly people (M 88.0±5.0 yrs) into a SWV group and a control group. The SWV group conducted 10 minutes of SWV per day, 5 days a week for 8 consecutive weeks. For evaluation purposes, we analyzed the moods with TDMS, heart rate variability (HRV), resting energy expenditure (REE), and brain activation during the Stroop test using near-infrared spectroscopy (NIRS).

Results: The stability level and pleasure level of mood increased significantly immediately after SWV. Simultaneously, the levels of the parasympathetic nervous system index of HRV significantly increased while the levels of the sympathetic nervous system index significantly decreased. REE also significantly increased. These results suggest that SWV has a relaxation effect as well as increasing the energy expenditure for elderly people. After intervention, Stroop B's execution time significantly decreased suggesting an improvement in the processing speed. The NIRS revealed that SWV may therefore activate the frontal lobe function.

Conclusions: These results suggest that SWV may have a positive effect on mood, the autonomic nervous system, cognitive function and brain functions, and thus such treatment may be useful for elderly people.
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http://dx.doi.org/10.3143/geriatrics.57.441DOI Listing
January 2021

[Effects of facial rehabilitation exercise on the mood, facial expressions, and facial muscle activities in patients with Parkinson's disease].

Nihon Ronen Igakkai Zasshi 2019 ;56(4):478-486

Graduate School of Comprehensive Human Science, Department of Social Health and Stress Management, University of Tsukuba.

Aim: Facial expressions are often impaired in patients with Parkinson's disease (PD). Few studies have examined the effects of head and neck rehabilitation in patients with PD using a facial expression analysis. In the present study, to further elucidate the effects of facial rehabilitation exercise in patients with PD, a three-dimensional facial expression analysis with FaceReader™ and surface electromyography (EMG) were performed in order to assess the facial expressions and muscle activities, respectively. The effects of such exercises on the mood and mental health were also evaluated.

Method: Twenty-one patients with PD (63.3±12.1 years) participated in the present study and were randomly assigned to an intervention group and non-intervention group. Facial rehabilitation exercise was performed for 60 minutes once a week for 12 weeks in the intervention group. GHQ-12, the facial expression analysis with FaceReader™, surface EMG, and the VAS scale for mood changes were used to evaluate the effects of the program. The results from both groups were compared.

Results: The results from eight patients in the intervention group and five in the non-intervention group were analyzed. FaceReader™ revealed a higher "Happy" index and lower "Sad" index in the intervention group than in the non-intervention group, and a significant interaction "Happy" index by an analysis of variance was noted between the two groups. EMG also showed increases in the activity of facial muscles in the intervention group. The subjects' mood improved after each facial rehabilitation exercise session.

Conclusion: The results of the present study suggest that the facial rehabilitation exercise affected the mood, facial expression, and facial muscle activities in patients with PD and indicate that the expression analysis with the FaceReader™ and surface EMG are useful for evaluating the effects of facial rehabilitation exercise.
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http://dx.doi.org/10.3143/geriatrics.56.478DOI Listing
March 2020

General Mental Health Is Associated with Gait Asymmetry.

Sensors (Basel) 2019 Nov 10;19(22). Epub 2019 Nov 10.

Institute for Health and Sport (IHeS), Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia.

Wearable sensors are being applied to real-world motion monitoring and the focus of this work is assessing health status and wellbeing. An extensive literature has documented the effects on gait control of impaired physical health, but in this project, the aim was to determine whether emotional states associated with older people's mental health are also associated with walking mechanics. If confirmed, wearable sensors could be used to monitor affective responses. Lower limb gait mechanics of 126 healthy individuals (mean age 66.2 ± 8.38 years) were recorded using a high-speed 3D motion sensing system and they also completed a 12-item mental health status questionnaire (GHQ-12). Mean step width and minimum foot-ground clearance (MFC), indicative of tripping risk, were moderately correlated with GHQ-12. Ageing and variability (SD) of gait parameters were not significantly correlated with GHQ-12. GHQ-12 scores were, however, highly correlated with left-right gait control, indicating that greater gait symmetry was associated with better mental health. Maintaining good mental health with ageing may promote safer gait and wearable sensor technologies could be applied to gait asymmetry monitoring, possibly using a single inertial measurement unit attached to each shoe.
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http://dx.doi.org/10.3390/s19224908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891551PMC
November 2019

[Possible relationship between prescription medications and urinary dysfunction in elderly home health care patients].

Nihon Ronen Igakkai Zasshi 2019 ;56(3):301-311

Graduate School of Comprehensive Human Sciences, University of Tsukuba.

Aim: Although urinary incontinence (UI) in the elderly appears to be related to polypharmacy, it is unclear whether multiple medications elevate UI quantitatively or qualitatively. There have been few studies on the association of polypharmacy with each type of UI. The present survey aimed to clarify these issues.

Method: The subjects were elderly home health care patients ≥65 years of age taking ≥5 prescription medications and not being treated with anti-cancer agent. The visiting nurses filled out a questionnaire based on their nursing and medication records. Types of UI were evaluated according to a UI checklist.

Results: A total of 167 subjects (97 women, 70 men, mean age of 83.8 years) were eligible for the data analysis. Subjects talking 5-9 prescription medications accounted for 59.3%, while those talking≥10 counted for 40.7%. Men talking ≥10 medications showed a slight but non-significant increased risk of UI. In women, α-adrenergic antagonists and benzodiazepines significantly increased the risk of stress UI and urge UI, respectively. Furthermore, α-adrenergic antagonists reduced the risk of functional UI, whereas acetylcholinesterase inhibitors elevated it. α-adrenergic antagonists in combination with benzodiazepines also significantly increased the risk of stress UI and urge UI, while α-adrenergic antagonists with acetylcholinesterase inhibitors increased the risk of stress UI. In men, there were no prescription medications that were particularly related to UI.

Conclusions: The present results suggest that there are gender differences in prescription medications-induced UI. It is likely that the causing medications are different depending on the type of UI, and the combination of them significantly increase the risk of UI.
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http://dx.doi.org/10.3143/geriatrics.56.301DOI Listing
February 2020

[Effects of drug treatment on the surviral-time in patients with dementia].

Nihon Ronen Igakkai Zasshi 2019 ;56(2):171-180

Department of Community-based Medicine, Nagoya City University Graduate School of Medicine.

Aim: The effect of polypharmacy on the surviral-time in patients with dementia has never been fully elucidated.

Methods: A retrospective study was conducted in a hospital in Aichi, Japan, by reviewing the medical charts and autopsy reports. Patients were hospitalized and neuropathologically diagnosed with dementia. The data on medication was collected from the prescribed drugs taking right before the admission. Patients were divided into two groups according to the number of prescribed drugs: ≥ 5 drugs (polypharmacy) vs. ≤ 4 drugs (non-polypharmacy). "Drugs to be prescribed with special caution" were defined in accordance with the guidelines for medical treatment and its safety in the elderly (2015).

Results: Seventy-six patients were eligible, and 39.5% of patients had polypharmacy. The Kaplan-Meier method showed that the polypharmacy group tended to have a shorter survival-time than the non-polypharmacy group (p=0.067). A Cox proportional hazard model showed that the polypharmacy group tended to have a higher risk for a reduced survival-time than the non-polypharmacy group, and this tendency was more prominent after adjusting for sex and age at admission (adjusted hazard ratio, 1.631; 95% confidence interval, 0.991-2.683; p=0.054). "Drugs to be prescribed with special caution", including hypnotic-sedative drugs, antianxiety drugs, antipsychotics, and benzodiazepines, were not found to be risk factors for a reduced survival-time.

Conclusions: The present study showed that polypharmacy in terminal patients with dementia tended to carry a risk for reducing their remaining lifespan. The results warrant further additional study.
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http://dx.doi.org/10.3143/geriatrics.56.171DOI Listing
March 2020

Pneumonia-associated death in patients with dementia: A systematic review and meta-analysis.

PLoS One 2019 14;14(3):e0213825. Epub 2019 Mar 14.

Waseda University Organization of Regional and Inter-Regional Studies, Tokyo, Japan.

Background: Pneumonia is a serious disease associated with mortality among patients with dementia. However, the reported frequency of pneumonia as a cause of death in patients with dementia varies, the reason for which has not been fully elucidated.

Methods: We conducted a systematic search in PubMed and the Cochrane Database of Systematic Reviews (inception to December 2016). Two authors independently determined the suitability of studies and potential bias and extracted the data. The primary outcome was frequency of pneumonia-associated death in patients with dementia. Stratified subgroup analysis was conducted among studies grouped according to type of mortality cause (immediate or underlying), information source of mortality cause (autopsy or death certificate), and study setting (clinic, hospital, or nursing home).

Results: We included 7 studies reporting the cause of death among patients with dementia and 12 studies comparing the cause of death among patients with and without dementia. The frequency of pneumonia-associated death among 19 eligible studies was 29.69% (95% confidence interval [CI], 25.86-33.53). Those frequencies differed according to whether the source for information about cause of death was an autopsy confirmation (49.98%; 95% CI, 43.75-56.71) or death certificate (19.65%; 95% CI, 15.48-23.83) and according to whether the type of mortality cause was an indirect cause of death (13.96%; 95% CI, 9.42-18.51) or direct cause of death (44.45%; 95% CI, 29.81-50.10). The risk of pneumonia-associated death in patients with dementia was twice as high as among those without dementia (odds ratio, 2.15; 95% CI, 1.63-2.83; p < 0.001).

Conclusion: The various frequencies of pneumonia-associated death in patients with dementia were associated with the information source, type of mortality cause, and study setting. Patients with dementia in the terminal stages urgently require careful clinical management of pneumonia, to maximize patient life expectancy and quality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213825PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417730PMC
December 2019

Factors influencing hospital admission among patients with autopsy-confirmed dementia.

Psychogeriatrics 2019 May 24;19(3):255-263. Epub 2019 Jan 24.

Department of Social Health and Stress Management, University of Tsukuba, Graduate School of Comprehensive Human Science, Tsukuba, Japan.

Background: The symptoms of geriatric syndromes and the behavioural and psychological symptoms of dementia (BPSD), in addition to clinical conditions, are associated with hospital admission among dementia patients. However, the principal factors that necessitate hospital admission among dementia patients have not been fully elucidated.

Methods: We retrospectively reviewed the data in the medical and autopsy reports of patients who had been treated at a hospital in Toyohashi, Japan. Each patient had been hospitalized sometime between 2012 and 2016 and underwent a brain autopsy. Dementia and the subtypes of dementia were diagnosed neuropathologically. Information about patients' general backgrounds, clinical conditions at the time of admission, and the geriatric syndrome symptoms and BPSD before admission was collected; comparisons were then made between patients with and without dementia and among those with the different major subtypes of dementia. Then, the factors relating to hospital admission of dementia patients were comprehensively evaluated by using principle component analysis.

Results: Of the 128 eligible patients, 100 (78.1%) had dementia. In the comparison of patients with and without dementia, patients without dementia were younger at both admission (P = 0.034) and death (P = 0.003). Among the patients with dementia with Lewy bodies, delusions had a significantly high prevalence (P = 0.014). Principal component analysis identified nine components (disinhibition, irritability/lability, agitation/aggression, anxiety, delusions, sleep/night-time behaviour disorders, hallucinations, aberrant motor behaviour, and speech impairment) as the principal factors related to hospital admission among dementia patients. Thus, BPSD were identified as principal factors.

Conclusions: Compared to other factors, BPSD are more likely to cause dementia patients to be admitted to hospital. The present results indicate that measures should be taken to ameliorate the difficulties associated with caring for patients with BPSD at home.
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http://dx.doi.org/10.1111/psyg.12393DOI Listing
May 2019

[A case of late-onset paraphrenia in a very elderly patient receiving home medical care].

Nihon Ronen Igakkai Zasshi 2018 ;55(4):675-678

Graduate School of Comprehensive Human Science, Faculty of Health and Sports Sciences, University of Tsukuba.

A 94 year old woman with a late-onset paraphrenia was referred to our clinic from a community care center. The patient showed symptoms of paranoia and auditory hallucination. The patient was in conflict with her neighbors regarding noise-related problems and was experiencing loss of appetite. Because the patient had a strong aversion to outpatient treatment due to difficulty in commuting, home visits were commenced. Improvements were observed after administration of 2.5 mg per day of olanzapine.In home medical care, precise definitive diagnosis and determination of treatment approach is necessary under limited time and resources. The fact that elderly people often exhibit psychological symptoms such as hallucinations is well known among clinical professions. However, this is not well known among home care patients, families and other professionals, and, therefore, is often overlooked. As the population ages further, it can be predicted that cases of elderly patients requiring treatment for psychological symptoms will increase in home medical care situations. In Japan, with a super-aging society, understanding and continuously supporting late-onset paraphrenia among elderly people is a pressing issue for all communities in advancing home medical care and nursing.
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http://dx.doi.org/10.3143/geriatrics.55.675DOI Listing
April 2019

Imaging studies of kleptomania in a middle-aged woman with obsessive-compulsive disorder: a case report.

Psychogeriatrics 2018 Sep 10;18(5):430-433. Epub 2018 Jul 10.

Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

A 57-year-old woman who had been arrested for shoplifting visited our hospital. She was diagnosed with kleptomania. She had previously been diagnosed with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and obsessive-compulsive disorder. Cranial magnetic resonance imaging showed mild atrophy of the bilateral dorsolateral prefrontal cortices, left hippocampus, and occipital cortex, as well as diffuse mild T hyperintensity in the deep and subcortical white matter, including the frontal region. During a single-photon emission computed tomography scan, significant hyperperfusion was observed in the right ventral striatum, including the nucleus accumbens, ventral thalamus, and right ventrolateral prefrontal areas. Patchy hypoperfusion was found in the bilateral posterior cingulate, parietal, and occipital regions. The patient's neurocognitive function was normal, except for slight impairment of her executive function. Her symptoms and neuroimaging findings were not suggestive of a specific neurocognitive disorder. Hyperactivity of the right ventral striatum may contribute to both obsessive-compulsive disorder and kleptomania. Although frontotemporal lobar degeneration is a major neurocognitive disorder related to illegal behaviours, CREST syndrome-induced white matter microstructural damage in the orbitofrontal lobe could have caused our patient's kleptomania.
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http://dx.doi.org/10.1111/psyg.12339DOI Listing
September 2018

I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study.

J Neurol Neurosurg Psychiatry 2018 11 31;89(11):1167-1173. Epub 2018 May 31.

Division of Cardiovascular Medicine, Department of Internal Medicine, Ohmori Hospital, Toho University School of Medicine, Tokyo, Japan.

Background And Purpose: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine (I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of I-MIBG scintigraphy in differentiation of probable DLB from probable AD.

Methods: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of I-MIBG scintigraphy performed at baseline.

Results: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline.

Conclusions: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested.

Trial Registration Number: UMIN00003419.
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http://dx.doi.org/10.1136/jnnp-2017-317398DOI Listing
November 2018

[The effective of facial exercises on the mental health in elderly adults].

Nihon Ronen Igakkai Zasshi 2018 ;55(1):74-80

Doctoral Program in Human Care Science. Graduate School of Comprehensive Human Sciences, University of Tsukuba.

Aim: Although it is well documented that exercising is good for the mental health and cognitive function as well as the physical condition in elderly people, exercising is difficult in elderly individuals with a low motor function. To develop an exercise program targeting elderly individuals unsuited for whole-body exercises, we assessed the effects of facial exercises on the mental health in healthy elderly people.

Methods: Community-dwelling older adults (N = 75, age range = 65-87 years) were randomly divided into a facial exercises group and a wait-listed control group. A facial exercises program of 30 min was given twice a week for 12 weeks. This program consisted of rhythmic facial movement, muscle stretching, facial yoga, and Tanden breathing. The GHQ-12 for mental health were administered to both groups before and after the 12-week study period. In addition, the facial expression and tongue muscle power were measured.

Results: Fifty-three participants completed the protocol. In the intervention group, the GHQ-12, facial expression, and tongue muscle power improved post-intervention.

Conclusions: These results suggest that facial exercises are effective in improving the mental health, facial expression, tongue muscle power of elderly people, and that exercises may be useful as a therapeutic modality in this population.
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http://dx.doi.org/10.3143/geriatrics.55.74DOI Listing
April 2019

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

Intern Med 2017 15;56(8):907-914. Epub 2017 Apr 15.

Department of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Japan.

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.
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http://dx.doi.org/10.2169/internalmedicine.56.7879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465406PMC
June 2017

Prognostic Factors Related to Dementia with Lewy Bodies Complicated with Pneumonia: An Autopsy Study.

Intern Med 2016;55(19):2771-2776. Epub 2016 Oct 1.

Department of Social Health and Stress Management, Graduate School of Comprehensive Human Science, University of Tsukuba, Japan.

Objective In patients demonstrating dementia with Lewy bodies (DLB), pneumonia is a common complication. However, the prognostic factors for the survival time in DLB with pneumonia have not been investigated by autopsy in patients with neuropathologically confirmed DLB. Methods We conducted a retrospective study of the medical and autopsy reports of 42 patients admitted to a Japanese hospital between 2005 and 2014. The patients were neuropathologically diagnosed as having DLB by post-mortem examinations. We analyzed the effects of various factors on the time from DLB onset to death. Results Thirty-nine of the 42 patients with DLB (92.9%) developed pneumonia during hospitalization. The median age at DLB onset was 78 years and the median time from DLB onset to death was 8 years. The Cox proportional hazard model demonstrated cerebral infarction [Hazard Ratio (HR), 2.36 (95% CI 1.12-4.96), p=0.023], muscle weakness [HR, 2.04 (0.95-4.39), p=0.067], male sex [HR, 2.84 (1.24-6.50), p=0.014], and age at onset (≥78 years.) [HR, 4.71 (1.82-12.18), p=0.001] to be prognostic factors for a shorter time from DLB onset to death. Conclusion Careful treatment of cerebral infarction and muscle weakness of the lower extremities is crucial for DLB patients with pneumonia, especially for those over 78 years of age, in order to maximize the patients' life expectancies.
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http://dx.doi.org/10.2169/internalmedicine.55.6868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088536PMC
February 2017

Screening Tool for Older Persons' Appropriate Prescriptions for Japanese: Report of the Japan Geriatrics Society Working Group on "Guidelines for medical treatment and its safety in the elderly".

Geriatr Gerontol Int 2016 09;16(9):983-1001

Department of Geriatric Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

Aim: In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the "Guidelines for medical treatment and its safety in the elderly 2005." The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required.

Methods: A total of 15 diseases, conditions and special areas related to their clinical care were selected. We originated clinical questions and keywords for these 15 areas, carried out a systematic review using these search criteria, and formulated guidelines applying the Grading of Recommendations Assessment, Development and Evaluation system advocated by Minds2014. If we did not find good evidence despite the drug being clinically important, we looked for evidence of efficacy and for disease-specific guidelines, and incorporated them into our guidelines.

Results: We selected 2098 articles (140 articles per area), and extracted another 186 articles through a manual search. We further added guidelines based on disease entity and made two lists, one of "drugs to be prescribed with special caution" and the other of "drugs to consider starting," primarily considering individuals aged 75 years or older or those who are frail or in need of special care.

Conclusions: New lists of potentially inappropriate medications and potential prescribing omissions called "Screening Tool for Older Person's Appropriate Prescriptions for Japanese" were constructed. We anticipate that future studies will highlight more evidence regarding the safety of high-quality drugs, further improving the provision of appropriate medical care for the elderly. Geriatr Gerontol Int 2016: 16: 983-1001.
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http://dx.doi.org/10.1111/ggi.12890DOI Listing
September 2016

Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline.

Alzheimers Dement (Amst) 2015 Jun 15;1(2):270-80. Epub 2015 Jun 15.

Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Introduction: There are no blood-based biomarkers for cognitive decline in aging, or mild cognitive impairment (MCI) and Alzheimer's disease (AD). Cumulative evidence suggests that apolipoproteins, complement system, and transthyretin are involved in AD pathogenesis by sequestration of amyloid β. However, there is no clinical study to assess the utility of "sequester proteins" in risk assessment and/or diagnosis of MCI and AD.

Methods: Serum levels of sequester proteins and their clinical potential in cognitive decline assessment were analyzed by longitudinal and cross-sectional studies using independent cohorts and were confirmed by a prospective study.

Results: A combination of apolipoprotein A1, complement C3, and transthyretin achieved an area under the curve of 0.89 (sensitivity 91% and specificity 80%) in MCI versus healthy controls and also discriminated individuals with mild cognitive decline from healthy controls.

Discussion: A set of sequester proteins could be blood-based biomarkers for assessment of early stages of cognitive decline.
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http://dx.doi.org/10.1016/j.dadm.2015.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876892PMC
June 2015

Impact of Depressive Symptoms on Conversion from Mild Cognitive Impairment Subtypes to Alzheimer's Disease: A Community-Based Longitudinal Study.

J Alzheimers Dis 2016 ;51(2):405-15

Department of Neuropsychiatry, University of Tsukuba, Ibaraki, Japan.

Background: While longitudinal studies have investigated the relationships between mild cognitive impairment (MCI) subtypes and dementia subtypes, the results have been contradictory. In addition, some research shows that depression accompanied by MCI might increase the risk of Alzheimer's disease (AD).

Objective: The aim of this study is to longitudinally investigate the relationships between MCI subtypes and dementia subtypes, with special attention to the effect of comorbid depressive symptoms in a Japanese rural community.

Methods: Non-demented participants (n = 802) completed a baseline and follow-up study. Outcomes were conversion to dementia especially AD, MCI, or no conversion. A complementary log-log analysis was conducted to investigate the risk of dementia and AD in amnestic MCI (aMCI) compared to nonamnestic MCI (naMCI) groups. The impact of depressive symptoms on the transition from MCI to AD and from cognitively normal to MCI or AD was also analyzed.

Results: The risk of developing dementia, in particular AD, for the aMCI group was significantly higher than that for the naMCI group. In the aMCI group, the presence of depressive symptoms increased the risk of developing AD, but depressive symptoms in the naMCI group did not. In the cognitively normal group, the presence of depressive symptoms increased the risk of aMCI but not naMCI or AD.

Conclusion: MCI subtyping could be useful in finding a prodrome for dementia and in particular for AD. The differing impacts of depressive symptoms on the development of AD suggest that the relationship between depressive symptoms and cognitive impairment could differ in aMCI and naMCI patients.
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http://dx.doi.org/10.3233/JAD-150603DOI Listing
December 2016

Ventilatory Response to Hypercapnia Predicts Dementia with Lewy Bodies in Late-Onset Major Depressive Disorder.

J Alzheimers Dis 2016 ;50(3):751-8

Tokyo Medical and Dental University, Tokyo, Japan.

Background: Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB.

Objective: Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD.

Methods: Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123I-meta-iodobenzylguanidine scintigraphy.

Results: Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters.

Conclusion: In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB.
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http://dx.doi.org/10.3233/JAD-150507DOI Listing
October 2016

[From "Guidelines for Medical Treatment and Its Safety in the Elderly 2015"].

Seishin Shinkeigaku Zasshi 2016 ;118(11):841-844

"Guidelines for medical treatment and its safety in the elderly 2015" are the guidelines that position safety as the principal objective when a non-specialist performs medical therapy for elderly persons older than 75 years old, or an elderly person who is frail or needs nursing care younger than 75 years. When the guidelines were announced in April 2015, many public comments were received from patients, caregivers, care staff, medical doctors, and the medical society. The majority of the comments were regarding behavioral and psychological symptoms of dementia (BPSD). Many opinions about antipsychotics were from non-specialists, such as primary care doctors. This suggests that many non-specialists treat severe BPSD using antipsychotics, and that the further promotion of cooperation between non-specialists and psychiatrists is necessary.
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March 2019

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and vascular dementia.

Psychogeriatrics 2016 Sep 29;16(5):305-14. Epub 2015 Oct 29.

Department of Pulmonary Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.

Background: Pneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated.

Methods: We retrospectively analyzed the data from medical and autopsy reports. All study patients had been hospitalized and underwent brain autopsy in a hospital in Toyohashi, Japan, between 2005 and 2014. The patients with subtypes of dementia, specifically Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), were neuropathologically diagnosed and examined. Pneumonia incidence, cause of death, and the clinical time-course of dementia were compared among the dementia subtypes. The time to death from dementia onset (survival time) was compared by the Kaplan-Meier method among subtypes of dementia with or without pneumonia. Risk factors for survival time on all study patients were analyzed with the Cox proportional hazard model.

Results: Of the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan-Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD.

Conclusions: Pneumonia complications shortened the survival time of patients with AD, DLB, and VaD.
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http://dx.doi.org/10.1111/psyg.12163DOI Listing
September 2016

Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease.

Neuropathology 2016 Apr 21;36(2):135-45. Epub 2015 Aug 21.

Departments of Neurology, University of Pittsburgh, Pittsburgh, USA.

Studies of acetylcholine degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in Alzheimer's disease (AD) have suggested their potential role in the development of fibrillar amyloid-β (Aβ) plaques (amyloid plaques). A recent genome-wide association study analysis identified a novel association between genetic variations in the BCHE locus and amyloid burden. We studied BChE immunoreactivity in hippocampal tissue sections from AD and control cases, and examined its relationship with amyloid plaques, neurofibrillary tangles (NFT), dystrophic neurites (DN) and neuropil threads (NT). Compared to controls, AD cases had greater BChE immunoreactivity in hippocampal neurons and neuropils in CA2/3, but not in the CA1, CA4 and dentate gyrus. The majority of amyloid plaques (> 80%, using a pan-amyloid marker X-34) contained discrete neuritic clusters which were dual-labeled with antibodies against BChE and phosphorylated tau (clone AT8). There was no association between overall regional BChE immunoreaction intensity and amyloid plaque burden. In contrast to previous reports, BChE was localized in only a fraction (~10%) of classic NFT (positive for X-34). A similar proportion of BChE-immunoreactive pyramidal cells were AT8 immunoreactive. Greater NFT and DN loads were associated with greater BChE immunoreaction intensity in CA2/3, but not in CA1, CA4 and dentate gyrus. Our results demonstrate that in AD hippocampus, BChE accumulates in neurons and plaque-associated neuritic clusters, but only in a small proportion of NFT. The association between greater neurofibrillary pathology burden and markedly increased BChE immunoreactivity, observed selectively in CA2/3 region, could reflect a novel compensatory mechanism. Since CA2/3 is generally considered more resistant to AD pathology, BChE upregulation could impact the cholinergic modulation of glutamate neurotransmission to prevent/reduce neuronal excitotoxicity in AD hippocampus.
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http://dx.doi.org/10.1111/neup.12241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761534PMC
April 2016

Relationship between Dementia Severity and Behavioral and Psychological Symptoms of Dementia in Dementia with Lewy Bodies and Alzheimer's Disease Patients.

Dement Geriatr Cogn Dis Extra 2015 May-Aug;5(2):244-52. Epub 2015 Jun 6.

Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Tokyo, Japan.

Background/aims: Behavioral and psychological symptoms of dementia (BPSD) are common in the clinical manifestation of dementia. Although most patients with dementia exhibit some BPSD during the course of the illness, the association of BPSD with the stage of dementia remains unclear. It was the aim of this study to evaluate the impact of severity of dementia on the expression of BPSD in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Methods: Ninety-seven patients with DLB and 393 patients with AD were recruited from 8 dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric Inventory (NPI). A relationship between BPSD and dementia stage classified by the Clinical Dementia Rating (CDR) in each type of dementia was assessed.

Results: No significant difference was seen in NPI total score across CDR staging in the DLB group. On the other hand, the NPI total score significantly increased with dementia stage in the AD group.

Conclusion: The relationship of dementia stage with the expression of BPSD was different according to the type of dementia. BPSD and dementia stage were correlated in AD subjects, in whom psychiatric symptoms increase as the disease progresses, but not in DLB subjects.
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http://dx.doi.org/10.1159/000381800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483492PMC
July 2015

Diagnostic accuracy of 123I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study.

PLoS One 2015 20;10(3):e0120540. Epub 2015 Mar 20.

Division of Cardiovascular Medicine, Department of Internal Medicine, Ohmori Hospital, Toho University School of Medicine, Ota, Tokyo143-8541, Japan.

Background And Purpose: Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study.

Methods: We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system.

Results: Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio.

Conclusions: Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120540PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368705PMC
February 2016

Long-term mild-intensity exercise regimen preserves prefrontal cortical volume against aging.

Int J Geriatr Psychiatry 2015 Jul 29;30(7):686-94. Epub 2014 Oct 29.

Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Objectives: It has been suggested that exercise improves cognitive function and increases cerebral volume even in older people. However, the relation between cognitive function and brain volume is unclear. We evaluated the longitudinal change of cognitive function and gray matter volume due to mild-intensity exercise over 2 years, and the residual effects 6 months post-exercise.

Methods: Subjects were 110 healthy older individuals over 65 years old in Tone town, Ibaraki prefecture. Seventy-five participants were voluntarily enrolled in the exercise group. A mild-intensity calisthenics regimen, which consisted of home-based and club-based programs for as long as 2 years, was employed as the intervention for the exercise group.

Results: The exercise group showed significant improvement in attentional shift over the course of the observation period including a 6-month follow-up. Neuroimaging analysis revealed the significant preservation of bilateral prefrontal volume in the exercise group with small-volume corrections, although this effect faded after intervention. Furthermore, the longitudinal changes in attentional shift and memory were positively correlated with the prefrontal volumetric changes.

Conclusion: Our results suggest that mild-intensity exercise could prevent prefrontal volume reduction due to aging and impede cognitive decline.
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http://dx.doi.org/10.1002/gps.4205DOI Listing
July 2015

[Alzheimer's disease and depression].

Seishin Shinkeigaku Zasshi 2013 ;115(11):1122-6

Graduate School of Comprehensive Human Sciences, University of Tsukuba.

In Alzheimer's disease (AD) patients, depression is not rare. The prevalence of major depressive episodes has been reported to be within the range of 20-25% in AD patients, despite there being no association between the severity of AD and prevalence of comorbid depressive symptoms or diagnosed depression. Depression in AD patients is associated with greater impairment of the quality of life and an increased caregiver burden. As well as earlier placement in a nursing home, bio-psycho-social factors are also associated with the manifestation of depression in AD patients, and biological factors, such as the brain pathology, may be the main influence. Depressive mood, loss of interest, and anxiety are among the most marked symptoms of depression in AD patients. In comparison with major depressive disorder, in depression in AD, psychomotor retardation is more prominent, while, in major depressive disorder, somatic anxiety is more marked. In the treatment of depression in AD, non-pharmacological and pharmacological therapies are applied. Basically, support and encouragement are required. In addition, psychosocial interventions, such as validation, reminiscence, physical exercise, and interventions for caregivers of those with dementia have been reported to be useful. The results of RCT with antidepressants are inconsistent. As the efficacy of cholinesterase inhibitor for depression in AD has been reported, it is reasonable to initially provide treatment with cholinesterase inhibitors rather than antidepressant therapy.
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March 2014

Immunohistochemical analysis of ubiquilin-1 in the human hippocampus: association with neurofibrillary tangle pathology.

Neuropathology 2014 Feb 21;34(1):11-8. Epub 2013 Jul 21.

Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tokyo, Japan.

This post mortem immunohistochemical study examined the localization and distribution of ubiquilin-1 (UBL), a shuttle protein which interacts with ubiquitin and the proteasome, in the hippocampus from Alzheimer's disease (AD) dementia cases, and age-matched cases without dementia. In Braak stages 0-I-II cases, UBL immunoreactivity was detected in a dense fiber network in the neuropil, and in the cell cytoplasm and nucleoplasm of neurons in Cornu Ammonis (CA) fields and dentate gyrus granular neurons. In Braak stages III-IV and V-VI cases, UBL immunoreactivity was reduced in the neuropil and in the cytoplasm of the majority of CA1 neurons; some CA1 pyramidal neurons and the majority of CA2/3 pyramidal, CA4 multipolar, and dentate granular neurons had markedly increased UBL immunoreactivity in the nucleoplasm. Dual immunofluorescence analysis of UBL and antibody clone AT8 revealed co-localization most frequently in CA1 pyramidal neurons in Braak stage III-IV and V-VI cases. Further processing using the pan-amyloid marker X-34 revealed prominent UBL/X-34 dual labeling of extracellular NFT confined to the CA1/subiculum in Braak stage V-VI cases. Our results demonstrate that in AD hippocampus, early NFT changes are associated with neuronal up-regulation of UBL in nucleoplasm, or its translocation from the cytoplasm to the nucleus. The perseverance of UBL changes in CA2/3, CA4 and dentate gyrus, generally considered as more resistant to NFT pathology, but not in the CA1, may mark a compensatory, potentially protective response to increased tau phosphorylation in hippocampal neurons; the failure of such a response may contribute to neuronal degeneration in end-stage AD.
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http://dx.doi.org/10.1111/neup.12055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000263PMC
February 2014

Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [¹¹C]DAA1106.

Psychiatry Res 2012 Jul 11;203(1):67-74. Epub 2012 Aug 11.

Clinical Neuroimaging Section, Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.

Subjects with mild cognitive impairment (MCI) have "prodromal or incipient" dementia with neuropathological changes. Peripheral benzodiazepine receptor (PBR) binding was shown to reflect activated microglia, one of the predictive biomarkers of conversion to dementia. We sought to evaluate PBR binding in MCI subjects using positron emission tomography (PET). PET scans with [¹¹C]DAA1106, a potent and selective ligand for PBR, were performed on seven MCI subjects, 10 patients with Alzheimer's disease (AD) and 10 age-matched control subjects. PBR binding in the regions of interest was quantified by binding potential (BP). Five MCI subjects were clinically followed for 5 years after their initial PET scans. [¹¹C]DAA1106 binding to PBR was significantly increased in widespread areas in MCI subjects when compared to healthy controls. We found no significant difference in BP between MCI and AD patients. MCI subjects with [¹¹C]DAA1106 binding values higher than the control mean +0.5 standard deviation (S.D.) developed dementia within 5 years. Our finding of higher DAA binding in MCI subjects indicated that microglial activation may occur before the onset of dementia. In vivo detection of microglial activation may provide useful prognostic information with respect to stratifying MCI subjects at increased risk of dementia.
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http://dx.doi.org/10.1016/j.pscychresns.2011.08.013DOI Listing
July 2012

Combination of antioxidant supplements improved cognitive function in the elderly.

J Alzheimers Dis 2012 ;32(4):895-903

Department of Neuropsychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function.
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http://dx.doi.org/10.3233/JAD-2012-121225DOI Listing
August 2013
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