Wiley Acta Medica Okayama 0964-2633 70 3 2025 Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019) 329 336 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomokazu Inoue Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Taku Kurozumi Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Manabu Takaki Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryozo Kuwano Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Shigeru Suemitsu Asahigawaso Research Institute, Social Welfare Corporation Asahigawaso Background: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia. Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia. Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia. Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0533 149 1 2025 Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change 36 EN Osamu Yokota Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hanae Nakashima-Yasuda Okayama University Medical School Hideki Ishizu Okayama University Medical School Takashi Haraguchi Department of Neurology, National Hospital Organization Minami-Okayama Medical Center Akinori Miyashita Department of Molecular Genetics, Brain Research Institute, Niigata University Takeshi Ikeuchi Department of Molecular Genetics, Brain Research Institute, Niigata University Masato Hasegawa Dementia Research Project, Tokyo Metropolitan Institute of Medical Science Naoto Nishikawa Department of Neuropsychiatry, Okayama University Hospital Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 1 2025 令和５年度岡山医学会賞　脳神経研究奨励賞（新見賞） 1 3 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2755-9734 27 1 2024 Potential dopaminergic deficit in patients with geriatric psychiatric disorders as revealed by DAT-SPECT: a cross-sectional study 1 9 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Seishi Terada Department of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Naoto Nishikawa Department of Neuropsychiatry, Okayama University Hospital Tomoko Miki Department of Neuropsychiatry, Okayama University Hospital Osamu Yokota Department of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical Sciences Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical Sciences Background It has been reported that patients with geriatric psychiatric disorders include many cases of the prodromal stages of neurodegenerative diseases. Abnormal I-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT) reveals a nigrostriatal dopaminergic deficit and is considered useful to detect dementia with Lewy bodies and Parkinson's disease as well as progressive supranuclear palsy and corticobasal degeneration. We aimed to determine the proportion of cases that are abnormal on DAT-SPECT in patients with geriatric psychiatric disorders and to identify their clinical profile. Methods The design is a cross-sectional study. Clinical findings of 61 inpatients aged 60 years or older who underwent DAT-SPECT and had been diagnosed with psychiatric disorders, but not neurodegenerative disease or dementia were analysed. Results 36 of 61 (59%) had abnormal results on DAT-SPECT. 54 of 61 patients who had DAT-SPECT (89%) had undergone I-123-metaiodobenzylguanidine myocardial scintigraphy (I-123-MIBG scintigraphy); 12 of the 54 patients (22.2%) had abnormal findings on I-123-MIBG scintigraphy. There were no cases that were normal on DAT-SPECT and abnormal on I-123-MIBG scintigraphy. DAT-SPECT abnormalities were more frequent in patients with late-onset (55 years and older) psychiatric disorders (69.0%) and depressive disorder (75.7%), especially late-onset depressive disorder (79.3%). Conclusion Patients with geriatric psychiatric disorders include many cases showing abnormalities on DAT-SPECT. It is suggested that these cases are at high risk of developing neurodegenerative diseases characterised by a dopaminergic deficit. It is possible that patients with geriatric psychiatric disorders with abnormal findings on DAT-SPECT tend to show abnormalities on DAT-SPECT first rather than on I-123-MIBG scintigraphy. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2377 22 1 2022 Secondary autoimmune hypothalamitis with severe memory impairment 7 years after the onset of diabetes insipidus due to lymphocytic hypophysitis: a case report 371 EN Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Hospital Mayuko Senda Department of Neuropsychiatry, Okayama University Hospital Koichiro Yamamoto Department of General Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Sasaki Department of Neurology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seishi Terada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Norihito Yamada Department of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases. Case presentation A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion. Conclusion This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1015-6305 30 4 2020 Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases 811 830 EN Tomoko Miki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Yokota Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Haraguchi Department of Neurology, National Hospital Organization Minami‐Okayama Medical Center Hideki Ishizu Department of Laboratory Medicine and Pathology, Zikei Institute of Psychiatry Masato Hasegawa Dementia Research Project, Tokyo Metropolitan Institute of Medical Science Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Shu‐ichi Ueno Department of Neuropsychiatry, Ehime University Graduate School of Medicine Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0964-2633 64 12 2020 Validation of the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities 970 979 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences S. Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences R. Kuwano Asahigawaso Research Institute, Asahigawaso Medical Welfare Center T. Inoue Asahigawaso Research Institute, Asahigawaso Medical Welfare Center T. Kurozumi Asahigawaso Research Institute, Asahigawaso Medical Welfare Center A. Choju Asahigawaso Research Institute, Asahigawaso Medical Welfare Center S. Suemitsu Asahigawaso Research Institute, Asahigawaso Medical Welfare Center Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background, Dementia in people with intellectual disabilities (IDs) is difficult to detect because of preexisting cognitive deficits. An effective screening method is required. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was developed as an observer rating tool to screen dementia in people with ID. The aim of this study was to verify the screening accuracy of the DSQIID for Japanese people with ID. Methods Four‐hundred ninety‐three subjects with ID participated in this study. Caregivers who had observed the participants for more than 2 years scored the Japanese version of the DSQIID (DSQIID‐J) of the participants. Three doctors examined participants directly and diagnosed dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. To identify the key screening items that predict dementia, the specificities of a single and pairs of items with 100% sensitivity were evaluated relative to the dementia diagnosis. Results Of 493 participants, 34 were people with Down syndrome (DS), and 459 were people without DS. Seventeen participants were diagnosed with dementia. The suitable cut‐off score of the DSQIID‐J was 10/11 (sensitivity 100% and specificity 96.8%) for screening dementia. The inter‐rater reliability, test–retest reliability and internal consistency of the DSQIID‐J were excellent. Regarding key items, there was no single item with 100% sensitivity, and the best two‐item combination was the pair of ‘Cannot dress without help’ and ‘Walks slower’ (sensitivity 100% and specificity 93.5%). Conclusions We identified several important question items of the DSQIID‐J related to the diagnosis of dementia in people with ID. The DSQIID‐J is a useful screening tool for dementia in adults with ID. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 08856230 35 4 2020 Prevalence of dementia in people with intellectual disabilities: Cross‐sectional study 414 422 EN Shintaro Takenoshita Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryozo Kuwano Asahigawaso Research Institute, Asahigawa Medical Welfare Center Tomokazu Inoue Asahigawaso Research Institute, Asahigawa Medical Welfare Center Atsushi Cyoju Asahigawaso Research Institute, Asahigawa Medical Welfare Center Shigeru Suemitsu Asahigawaso Research Institute, Asahigawa Medical Welfare Center Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background There are only a few studies of the prevalence of dementia in people with intellectual disability (ID) without Down syndrome (DS), and there is a large difference in the prevalences between reported studies. Moreover, the prevalence of mild cognitive impairment (MCI) in ID has not been reported. We aimed to evaluate the prevalence of dementia in adults of all ages and the prevalence of MCI in people with ID. Furthermore, we tried to clarify the differences depending on the various diagnostic criteria. Methods The survey included 493 adults with ID at 28 facilities in Japan. The caregivers answered a questionnaire, and physicians directly examined the participants who were suspected of cognitive decline. Dementia and MCI were diagnosed according to ICD‐10, DC‐LD, and DSM‐5 criteria. Results The prevalence of dementia was 0.8% for the 45 to 54 years old group, 3.5% for the 55 to 64 years old group, and 13.9% for the 65 to 74 years old group in people with ID without DS. The prevalence of MCI was 3.1% for patients 45 to 54, 3.5% for patients 55 to 64, and 2.8% for patients 65 to 74 with ID without DS. DSM‐5 was the most inclusive in diagnosing dementia and MCI in people with ID. Conclusions People with ID without DS may develop dementia and MCI at an earlier age and higher rate than the general population. Among the diagnostic criteria, DSM‐5 was the most useful for diagnosing their cognitive impairment. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1346-3500 19 6 2019 Clinical characteristics of elderly depressive patients with low metaiodobenzylguanidine uptake 566 573 EN Shintaro Takenoshita Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seishi Terada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Etsuko Oshima Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Yamaguchi Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Hayashi Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Hinotsu Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Esumi Department of Pharmacy, Okayama University Hospital Takayoshi Shinya Department of Pediatric Radiology, Okayama University Hospital Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND: Recently, depression with Lewy body pathology before the appearance of parkinsonism and cognitive dysfunction has been drawing attention. Low cardiac metaiodobenzylguanidine (MIBG) uptake is helpful for early differentiation of Lewy body disease (LBD) from late-onset psychiatric disorders even before parkinsonism or dementia appears. In this study, we used MIBG uptake as a tool in suspected LBD, and evaluated the relationship of MIBG results to clinical characteristics and depressive symptoms. METHODS: Fifty-two elderly inpatients with depression were included in this study. The Hamilton Depression Rating Scale (HDRS) was administered at admission, and 123 I-MIBG cardiac scintigraphy was performed. Of 52 patients, 38 had normal and 14 had reduced MIBG uptake. RESULTS: Correlation analyses of the late phase heart-to-mediastinum (H/M) ratio on the MIBG test and each item of the HDRS revealed that the H/M ratio was significantly correlated with scores of 'agitation', 'anxiety-somatic', and 'retardation' on the HDRS. Mean HDRS composite scores of 'somatic and psychic anxiety (Marcos)' and 'somatic anxiety/somatization factor (Pancheri)' were higher in the low uptake group than in the normal uptake group. CONCLUSION: Elderly patients with depression who manifested an obvious somatic anxiety tend to show low MIBG uptake, and are more likely to have Lewy body pathology. No potential conflict of interest relevant to this article was reported.