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  1. Article ; Online: Anosognosia in patients with Alzheimer's disease: current perspectives.

    Tagai, Kenji / Nagata, Tomoyuki / Shinagawa, Shunichiro / Shigeta, Masahiro

    Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society

    2020  Volume 20, Issue 3, Page(s) 345–352

    Abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) ... ...

    Abstract Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.
    MeSH term(s) Aged ; Agnosia/diagnosis ; Agnosia/etiology ; Agnosia/psychology ; Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Awareness/physiology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Depression/diagnosis ; Depression/psychology ; Depressive Disorder/complications ; Depressive Disorder/psychology ; Humans ; Memory Disorders/etiology ; Memory Disorders/psychology ; Neurodegenerative Diseases ; Neuropsychological Tests
    Language English
    Publishing date 2020-01-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2213105-X
    ISSN 1479-8301 ; 1346-3500
    ISSN (online) 1479-8301
    ISSN 1346-3500
    DOI 10.1111/psyg.12507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Education level is associated with neuropsychiatric symptoms in patients with amnestic-mild cognitive impairment.

    Inamura, Keisuke / Shinagawa, Shunichiro / Nagata, Tomoyuki / Tagai, Kenji / Nukariya, Kazutaka / Shigeta, Masahiro

    Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society

    2022  Volume 22, Issue 3, Page(s) 343–352

    Abstract: Background: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to ... ...

    Abstract Background: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes.
    Methods: Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM).
    Results: Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years.
    Conclusions: Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions.
    MeSH term(s) Activities of Daily Living ; Alzheimer Disease/psychology ; Apathy ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Humans ; Neuropsychological Tests
    Language English
    Publishing date 2022-02-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2213105-X
    ISSN 1479-8301 ; 1346-3500
    ISSN (online) 1479-8301
    ISSN 1346-3500
    DOI 10.1111/psyg.12818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury.

    Miyata, Mari / Takahata, Keisuke / Sano, Yasunori / Yamamoto, Yasuharu / Kurose, Shin / Kubota, Manabu / Endo, Hironobu / Matsuoka, Kiwamu / Tagai, Kenji / Oya, Masaki / Hirata, Kosei / Saito, Fumie / Mimura, Masaru / Kamagata, Koji / Aoki, Shigeki / Higuchi, Makoto

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 7129

    Abstract: Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and ... ...

    Abstract Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV-adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK-SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann-Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10
    MeSH term(s) Humans ; Brain Concussion ; Mammillary Bodies ; Brain ; Memory Disorders/etiology ; Athletes/psychology ; Brain Injuries, Traumatic/complications
    Language English
    Publishing date 2024-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-57383-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Examining Frontal Lobe Asymmetry and Its Potential Role in Aggressive Behaviors in Early Alzheimer's Disease.

    Kameyama, Hiroshi / Tagai, Kenji / Takasaki, Emi / Kashibayashi, Tetsuo / Takahashi, Ryuichi / Kanemoto, Hideki / Ishii, Kazunari / Ikeda, Manabu / Shigeta, Masatoshi / Shinagawa, Shunichiro / Kazui, Hiroaki

    Journal of Alzheimer's disease : JAD

    2024  Volume 98, Issue 2, Page(s) 539–547

    Abstract: Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain ... ...

    Abstract Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain structural asymmetry could play a role in the appearance of NPS.
    Objective: This study explores the relationship between NPS and brain asymmetry in patients with Alzheimer's disease (AD).
    Methods: Demographic and MRI data for 121 mild AD cases were extracted from a multicenter Japanese database. Brain asymmetry was assessed by comparing the volumes of gray matter in the left and right brain regions. NPS was evaluated using the Neuropsychiatric Inventory (NPI). Subsequently, a comprehensive assessment of the correlation between brain asymmetry and NPS was conducted.
    Results: Among each NPS, aggressive NPS showed a significant correlation with asymmetry in the frontal lobe, indicative of right-side atrophy (r = 0.235, p = 0.009). This correlation remained statistically significant even after adjustments for multiple comparisons (p < 0.01). Post-hoc analysis further confirmed this association (p < 0.05). In contrast, no significant correlations were found for other NPS subtypes, including affective and apathetic symptoms.
    Conclusions: The study suggests frontal lobe asymmetry, particularly relative atrophy in the right hemisphere, may be linked to aggressive behaviors in early AD. These findings shed light on the neurobiological underpinnings of NPS, contributing to the development of potential interventions.
    MeSH term(s) Humans ; Alzheimer Disease/pathology ; Atrophy/pathology ; Brain/pathology ; Frontal Lobe/diagnostic imaging ; Frontal Lobe/pathology ; Magnetic Resonance Imaging
    Language English
    Publishing date 2024-02-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-231306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Progressive Ataxia and Palatal Tremor Showing Characteristic Tau Depositions in [

    Tezuka, Toshiki / Takahata, Keisuke / Tagai, Kenji / Ueda, Ryo / Ito, Daisuke / Takeda, Hidetaka / Takahashi, Shinichi / Nakahara, Jin / Higuchi, Makoto / Seki, Morinobu

    Movement disorders : official journal of the Movement Disorder Society

    2022  Volume 37, Issue 6, Page(s) 1317–1319

    MeSH term(s) Alzheimer Disease ; Ataxia/diagnostic imaging ; Humans ; Positron-Emission Tomography ; Tauopathies ; Tremor/diagnostic imaging ; tau Proteins/genetics
    Chemical Substances tau Proteins
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 607633-6
    ISSN 1531-8257 ; 0885-3185
    ISSN (online) 1531-8257
    ISSN 0885-3185
    DOI 10.1002/mds.28983
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: In vivo

    Kubota, Manabu / Endo, Hironobu / Takahata, Keisuke / Tagai, Kenji / Suzuki, Hisaomi / Onaya, Mitsumoto / Sano, Yasunori / Yamamoto, Yasuharu / Kurose, Shin / Matsuoka, Kiwamu / Seki, Chie / Shinotoh, Hitoshi / Kawamura, Kazunori / Zhang, Ming-Rong / Takado, Yuhei / Shimada, Hitoshi / Higuchi, Makoto

    Brain communications

    2024  Volume 6, Issue 2, Page(s) fcae075

    Abstract: Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. ...

    Abstract Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features.
    Language English
    Publishing date 2024-03-01
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcae075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Effects of neuropsychiatric symptoms of dementia on reductions in activities of daily living in patients with Alzheimer's disease.

    Okabe, Kiwamu / Nagata, Tomoyuki / Shinagawa, Shunichiro / Inamura, Keisuke / Tagai, Kenji / Nukariya, Kazutaka / Shigeta, Masahiro

    Geriatrics & gerontology international

    2020  Volume 20, Issue 6, Page(s) 584–588

    Abstract: Aim: In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ...

    Abstract Aim: In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD.
    Methods: Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model.
    Results: Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results.
    Conclusion: Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••-••.
    MeSH term(s) Activities of Daily Living/psychology ; Aged ; Aged, 80 and over ; Alzheimer Disease/psychology ; Cross-Sectional Studies ; Executive Function ; Female ; Humans ; Male ; Mental Status and Dementia Tests
    Language English
    Publishing date 2020-03-31
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2113849-7
    ISSN 1447-0594 ; 1444-1586
    ISSN (online) 1447-0594
    ISSN 1444-1586
    DOI 10.1111/ggi.13918
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  8. Article ; Online: Clinicodemographic and Psychosocial Factors Related to Presentation or Severity of Delusions of Theft among Females with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

    Inamura, Keisuke / Shinagawa, Shunichiro / Tsuneizumi, Yuri / Nagata, Tomoyuki / Tagai, Kenji / Nukariya, Kazutaka / Shigeta, Masahiro

    Clinical gerontologist

    2020  Volume 45, Issue 3, Page(s) 673–680

    Abstract: ... ...

    Abstract Objectives
    MeSH term(s) Activities of Daily Living ; Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Cognitive Dysfunction/psychology ; Delusions/psychology ; Female ; Humans ; Theft/psychology
    Language English
    Publishing date 2020-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 226146-7
    ISSN 1545-2301 ; 0731-7115
    ISSN (online) 1545-2301
    ISSN 0731-7115
    DOI 10.1080/07317115.2020.1720884
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Blood DNA Methylation Levels in the WNT5A Gene Promoter Region: A Potential Biomarker for Agitation in Subjects with Dementia.

    Kobayashi, Nobuyuki / Shinagawa, Shunichiro / Nagata, Tomoyuki / Tagai, Kenji / Shimada, Kazuya / Ishii, Azusa / Oka, Naomi / Shigeta, Masahiro / Kondo, Kazuhiro

    Journal of Alzheimer's disease : JAD

    2021  Volume 81, Issue 4, Page(s) 1601–1611

    Abstract: Background: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. ... ...

    Abstract Background: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined.
    Objective: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation.
    Methods: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis.
    Results: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines.
    Conclusion: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.
    Language English
    Publishing date 2021-05-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-210078
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  10. Article ; Online: Altered Brain Energy Metabolism Related to Astrocytes in Alzheimer's Disease.

    Hirata, Kosei / Matsuoka, Kiwamu / Tagai, Kenji / Endo, Hironobu / Tatebe, Harutsugu / Ono, Maiko / Kokubo, Naomi / Oyama, Asaka / Shinotoh, Hitoshi / Takahata, Keisuke / Obata, Takayuki / Dehghani, Masoumeh / Near, Jamie / Kawamura, Kazunori / Zhang, Ming-Rong / Shimada, Hitoshi / Yokota, Takanori / Tokuda, Takahiko / Higuchi, Makoto /
    Takado, Yuhei

    Annals of neurology

    2023  

    Abstract: Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to ...

    Abstract Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism. Astrocytes are primarily considered glycolytic cells, suggesting a preference for lactate production. This study aimed to examine alterations in astrocytic activities and their association with brain lactate levels in AD.
    Methods: The study included 30 AD and 30 cognitively unimpaired participants. For AD participants, amyloid and tau depositions were confirmed by positron emission tomography using [
    Results: Myo-inositol and lactate levels were higher in AD patients than in cognitively unimpaired participants (p < 0.05). Myo-inositol levels correlated with lactate levels (r = 0.272, p = 0.047). Myo-inositol and lactate levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores (p < 0.05). Significant correlations were noted between myo-inositol levels and plasma glial fibrillary acidic protein, tau phosphorylated at threonine 181 levels, and amyloid and tau positron emission tomography accumulation in the posterior cingulate cortex (p < 0.05).
    Interpretation: We found high myo-inositol levels accompanied by increased lactate levels in the posterior cingulate cortex in AD patients, indicating a link between reactive astrocytes and altered brain energy metabolism. Myo-inositol and plasma glial fibrillary acidic protein may reflect similar astrocytic changes as biomarkers of AD. ANN NEUROL 2023.
    Language English
    Publishing date 2023-09-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.26797
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