School of Medicine, Center for Supercentenarian Medical Research Center for Supercentenarian Medical Research (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

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  • Plasma phospholipid n-3 polyunsaturated fatty acids and major depressive disorder in Japanese elderly: the Japan Public Health Center-based Prospective Study

    Hamazaki K., Matsuoka Y.J., Yamaji T., Sawada N., Mimura M., Nozaki S., Shikimoto R., Tsugane S.

    Scientific Reports (Scientific Reports)  11 ( 1 )  2021.12

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    The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on depression are not definitively known. In a previous population-based prospective cohort study, we found a reverse J-shaped association of intake of fish and docosapentaenoic acid (DPA), the intermediate metabolite of EPA and DHA, with major depressive disorder (MDD). To examine the association further in a cross-sectional manner, in the present study we analyzed the level of plasma phospholipid n-3 PUFAs and the risk of MDD in 1,213 participants aged 64–86 years (mean 72.9 years) who completed questionnaires and underwent medical check-ups, a mental health examination, and blood collection. In multivariate logistic regression analysis, odds ratios and 95% confidence intervals were calculated for MDD according to plasma phospholipid n-3 PUFA quartiles. MDD was diagnosed in 103 individuals. There were no significant differences in any n-3 PUFAs (i.e., EPA, DHA, or DPA) between individuals with and without MDD. Multivariate logistic regression analysis showed no significant association between any individual n-3 PUFAs and MDD risk. Overall, based on the results of this cross-sectional study, there appears to be no association of plasma phospholipid n-3 PUFAs with MDD risk in the elderly Japanese population.

  • Association between resilience and cortical thickness in the posterior cingulate cortex and the temporal pole in Japanese older people: A population-based cross-sectional study

    Shikimoto R., Noda Y., Kida H., Nakajima S., Tsugawa S., Mimura Y., Ochi R., Takayama M., Niimura H., Mimura M.

    Journal of Psychiatric Research (Journal of Psychiatric Research)  142   89 - 100 2021.10

    ISSN  00223956

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    Background: Resilience is a crucial factor preventing the onset of mental illness and contributing to the well-being and healthy longevity, whose neural bases are not fully elucidated in older people. The present study aimed to identify the cortical thickness associating with resilience in older adults. Methods: This is a part of the cross-sectional Arakawa geriatric cohort study for people aged 65 years or older, consisting of 1001 individuals. A Self-Reported Resilience Scale (RS), neuropsychological batteries, face-to-face interviews for diagnosis, and a three-dimensional T1-weighted magnetic resonance imaging were conducted. Cortical thickness was computed by the FreeSurfer. The relationships among cortical thickness, total RS score, and clinico-demographic data were investigated using univariate and multivariable regression analyses. Results: The total RS score was correlated with age, education, and scores of the Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) in univariate analyses. The total RS score was associated with cortical thicknesses in the left posterior cingulate (β [95 % CI of B] = 0.07 [0.16–14.84]) and the left temporal pole (β [95 % CI of B] = 0.08 [0.63–9.93]) after adjusting sex, age, imaging acquisition site, education, MMSE and GDS scores, hypertension, hyperlipidemia, diabetes mellitus, Barthel index, BMI, and living situation in multivariable regression analyses. Conclusion: The present analyses suggest that the resilience capacity may be related to the cortical thickness in the posterior cingulate and temporal cortices in older adults. Our findings warrant further longitudinal studies to confirm the causal relationship between stress events, resilience, and brain structures.

  • Caregiver self-efficacy and associated factors among caregivers of patients with dementia with Lewy bodies and caregivers of patients with Alzheimer's disease

    Sato H., Nakaaki S., Sato J., Shikimoto R., Furukawa T.A., Mimura M., Akechi T.

    Psychogeriatrics (Psychogeriatrics)   2021

    ISSN  13463500

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    Background: Dementia with Lewy bodies (DLB) is characterized by neuropsychiatric symptoms, which can be distressing to caregivers. However, little is known about their subjective distress in terms of caregiver self-efficacy. Thus, we examined the differences in caregiver self-efficacy and their associated factors between DLB and Alzheimer's disease (AD) caregivers. Methods: We conducted a comprehensive questionnaire for DLB and AD caregivers. Caregiver self-efficacy was evaluated using three domains (Self-Efficacy for Obtaining Respite: SE-OR, Self-Efficacy for Responding to Disruptive Patient Behaviours: SE-RDPB, Self-Efficacy for Controlling Upsetting Thoughts about Caregiving: SE-CUT) of the Revised Scale for Caregiving Self-Efficacy (RSCSE). In addition, data on the following features of caregivers were assessed: depression, sleep disturbance, caregiver burden, executive function, loneliness, social support, and distress associated with neuropsychiatric symptoms. The patients were assessed for general cognitive tasks, executive function, and neuropsychiatric symptoms. Results: Compared with AD caregivers, DLB caregivers experienced a significantly higher burden in terms of not only various clinical factors, but also all three domains of caregiver self-efficacy. Among the caregiver-associated factors, different domains were predictors of self-efficacy in DLB and AD caregivers (distress due to sleep disturbances in DLB patients; distress due to delusions in AD patients). Among the patient-associated factors, different domains were also predictors of self-efficacy in DLB and AD caregivers (sleep disturbances in DLB patients; delusions in AD patients). Among both the caregivers and the patients, executive function was a significant predictor of one RSCSE domain (SE-CUT). Conclusions: A reduction in caregiver self-efficacy may contribute to a severe subjective burden among DLB caregivers. Furthermore, two neuropsychiatric symptoms (delusions and sleep disturbances) affected caregiver self-efficacy differently depending on whether care was being provided to a DLB or AD patient. Understanding the association between specific neuropsychiatric symptoms and caregiver self-efficacy may be useful for conducting interventions for DLB patients.

  • Association between dietary fish and PUFA intake in midlife and dementia in later life: The JPHC Saku mental health study

    Nozaki S., Sawada N., Matsuoka Y.J., Shikimoto R., Mimura M., Tsugane S.

    Journal of Alzheimer's Disease (Journal of Alzheimer's Disease)  79 ( 3 ) 1091 - 1104 2021

    ISSN  13872877

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    Background: The relationship between midlife dietary habits and risk of dementia remains unclear. Objective: To investigate the association between dietary fish and n-3 polyunsaturated fatty acid (PUFA) consumption in midlife and risk of dementia in later life. Methods: This population-based cohort study assessed food frequency (average intake in 1995 and 2000) and cognition (2014-2015) in 1,127 participants (aged 45-64 in 1995). We used logistic regression analyses to calculate odds ratios (ORs) for dementia and mild cognitive impairment (MCI) diagnoses for consumption quartiles of fish, PUFA-rich fish, total n-3 PUFAs, total n-6 PUFAs, types of PUFAs, and n-3/n-6 PUFA ratio. Estimated ORs were adjusted for age; sex; education; smoking status; alcohol consumption frequency; physical activity; histories of cancer, myocardial infarction, and diabetes mellitus; and depression. Results: Significantly reduced risks of dementia over non-dementia (MCI plus cognitively normal) were observed in the second (OR = 0.43 (95% CI = 0.20-0.93)), third (OR = 0.22 (95% CI = 0.09-0.54)), and highest quartiles (OR = 0.39 (95% CI = 0.18-0.86)) for fish; the third (OR = 0.39 (95% CI = 0.16-0.92)) and highest quartiles (OR = 0.44 (95% CI = 0.19-0.98)) for eicosapentaenoic acid (EPA); the second (OR = 0.39 (95% CI = 0.18-0.84)), third (OR = 0.30 (95% CI = 0.13-0.70)), and highest quartiles (OR = 0.28 (95% CI = 0.12-0.66)) for docosahexaenoic acid (DHA); and the third (OR = 0.36 (95% CI = 0.16-0.85)) and highest quartiles (OR = 0.42 (95% CI = 0.19-0.95)) for docosapentaenoic acid (DPA). Conclusion: High intake of fish in midlife might aid in preventing dementia.

  • Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer’s disease

    Kobayashi N., Shinagawa S., Niimura H., Kida H., Nagata T., Tagai K., Shimada K., Oka N., Shikimoto R., Noda Y., Nakajima S., Mimura M., Shigeta M., Kondo K.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    Early diagnosis of dementia including Alzheimer’s disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

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