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Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders

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Abstract

To study the relationship between neurodegenerative diseases including argyrophilic grain disease (AGD) and late-onset schizophrenia and delusional disorders (LOSD; onset ≥40 years of age), we pathologically examined 23 patients with LOSD, 71 age-matched normal controls, and 22 psychiatric disease controls (11 depression, six personality disorder, two bipolar disorders, and three neurotic disorders cases). In all LOSD cases (compared to age-matched normal controls), the frequencies of Lewy body disease (LBD), AGD, and corticobasal degeneration (CBD) were 26.1 % (11.3 %), 21.7 % (8.5 %), and 4.3 % (0.0 %), respectively. There was no case of pure Alzheimer’s disease (AD). The total frequency of LBD, AGD, and CBD was significantly higher in LOSD cases than in normal controls. Argyrophilic grains were significantly more severe in LOSD than in controls, but were almost completely restricted to the limbic system and adjacent temporal cortex. In LOSD patients whose onset occurred at ≥65 years of age (versus age-matched normal controls), the frequencies of LBD and AGD were 36.4 % (19.4 %) and 36.4 % (8.3 %), respectively, and AGD was significantly more frequent in LOSD patients than in normal controls. In LOSD patients whose onset occurred at <65 years of age, the frequencies of LBD, AGD, and CBD were 16.7, 8.3, and 8.3 %, comparable to those of age-matched normal controls (10.2, 5.1, and 0.0 %). In all psychiatric cases, delusion was significantly more frequent in AGD cases than in cases bearing minimal AD pathology alone. Given these findings, LOSD patients may have heterogeneous pathological backgrounds, and AGD may be associated with the occurrence of LOSD especially after 65 years of age.

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Acknowledgments

We would like to thank Ms. Onbe (Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences) for her excellent technical assistance. This work was supported in part by Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Nos. 21591517, 23591708), and the Zikei Institute of Psychiatry.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Shigeto Nagao, Osamu Yokota, Chikako Ikeda, Naoya Takeda, Hideki Ishizu, Seishi Terada & Yosuke Uchitomi

  2. Zikei Institute of Psychiatry, Minami-ku, Okayama, 702-8508, Japan

    Hideki Ishizu & Shigetoshi Kuroda

  3. Department of Psychiatry, Tosa Hospital, Kochi, 780-0062, Japan

    Koichiro Sudo

  4. Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, 173-0015, Japan

    Shigeo Murayama

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  1. Shigeto Nagao
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Nagao, S., Yokota, O., Ikeda, C. et al. Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders. Eur Arch Psychiatry Clin Neurosci 264, 317–331 (2014). https://doi.org/10.1007/s00406-013-0472-6

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