Study on the clinical features of the prodromal stage of frontotemporal lobar degeneration

• Project/Area Number: 19K08045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Osaka University
• Principal Investigator: IKEDA MANABU 大阪大学, 医学系研究科, 教授 (60284395)
• Co-Investigator(Kenkyū-buntansha): 引田 咲良 大阪大学, 医学系研究科, 技術補佐員 (00834805) ; 鈴木 麻希 大阪大学, 連合小児発達学研究科, 寄附講座講師 (80422145) ; 釜江 和恵 大阪大学, 連合小児発達学研究科, 特任講師 (90553256)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 前頭側頭葉変性症 / 前頭側頭型認知症 / 行動異常型前頭側頭型認知症 / 意味性認知症 / バイオマーカー / Prodromal期 / 前頭側頭葉変性症（FTLD） / 前頭側頭型認知症（FTD） / 意味性認知症（SD） / サロゲートマーカー / 精神症状 / 行動変化 / Prodromal / prodroma

Outline of Research at the Start

アルツハイマー病やレビー小体型認知症と並んで4大認知症の1つである前頭側頭葉変性は、バイオマーカーが確立していない。Mild Cognitive Impairment（MCI）期ないしProdromal段階の症状すら明らかになっていない。 そこで、臨床あるいは病理学的に確定したFTLD例の臨床症状出現時のデータを検索し、初発症状となる可能性のある症状や神経画像の特徴を明らかにする。そして、認知症の診断基 準を満たさない初老期症例を、物忘れ外来、精神科専門外来を受診した患者の中から抽出し、 最低2年間追跡し、FTLDのProdromal期に特徴的なサロゲートマーカーならびにバイオマーカ ーを明らかにすると共に、Prodromal期の診断基準を作成する。

Outline of Final Research Achievements

The diagnosis of Frontotemporal dementia (FTD) in the prodromal stage remains challenging because of the limited evidence of clinical symptoms, and the limited accuracy of neuroimaging
We retrospectively investigated the clinical records and examined the neuropathology of FTD patients to identify symptoms appearing within 2 years of the first clinically apparent changes. It is seen in over 50% of early bvFTD patients, and distinct language features appear in the early stage of semantic dementia (SD). Both of them frequently present with additional symptoms, not included in the usual diagnostic criteria, such as physical signs, reticence, delusions.
We clarified the neuropsychiatric symptoms of right-sided predominant semantic dementia (SD-R) by comparing them with those of bvFTD, left-sided predominant SD (SD-L), Alzheimer’s disease (AD). SD-R seemed to be a similar condition to bvFTD rather than SD-L regarding behavioral symptoms, even in its early stage (Sato S et al, 2021).

Academic Significance and Societal Importance of the Research Achievements

前頭側頭型認知症において、発症ごく初期の症状を明らかにできたことにより、Prodromal期から出現していると考えられる症状が予測できるようになった。今後、アルツハイマー病のように疾患修飾薬の開発が順調に進めば、臨床試験の対象を今回明らかになった症状を指標にprodromal期から抽出できる可能性が出てきたと思われる。

Research Products

• [Journal Article] Distinct early symptoms in neuropathologically proven frontotemporal lobar degeneration (2021)
  • Author(s): Kawakami I, Arai T, Shinagawa S, Niizato K, Oshima K, Ikeda M
  • Journal Title: Int J Geriatr Psychiatry Volume: 36 Issue: 1 Pages: 38-45
  • DOI: 10.1002/gps.5387
  • Peer Reviewed / Open Access
• [Journal Article] The porphyrin TMPyP4 inhibits elongation during the noncanonical translation of the FTLD/ALS-associated GGGGCC repeat in the C9orf72 gene (2021)
  • Author(s): Mori K, Gotoh S, Yamashita T, Uozumi R, Kawabe Y, Tagami S, Kamp F, Nuscher B, Edbauer D, Haass C, Nagai Y, Ikeda M
  • Journal Title: J Biol Chem Volume: 297 Issue: 4 Pages: 101120-101120
  • DOI: 10.1016/j.jbc.2021.101120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characteristics of behavioral symptoms in right-sided predominant semantic dementia and their impact on caregiver burden: a cross-sectional study (2021)
  • Author(s): Sato S, Hashimoto M, Yoshiyama K, Kanemoto H, Hotta M, Azuma S, Suehiro T, Kakeda K, Nakatani Y, Umeda S, Fukuhara R, Takebayashi M, Ikeda M
  • Journal Title: Alzheimers Res Ther Volume: 13 Issue: 1 Pages: 166-166
  • DOI: 10.1186/s13195-021-00908-2
  • Peer Reviewed / Open Access
• [Journal Article] Research criteria for the diagnosis of prodromal dementia with Lewy bodies. (2020)
  • Author(s): McKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H, Kantarci K, Muscio C, O’Brien JT, Postuma RB, Tiraboschi P
  • Journal Title: Neurology Volume: 94 Issue: 17 Pages: 1-13
  • DOI: 10.1212/wnl.0000000000009323
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Non-fluent/Agrammatic Variant of Primary Progressive Aphasia with Generalized Auditory Agnosia (2020)
  • Author(s): Watanabe H, Ikeda M, Mori E
  • Journal Title: Front Neurol Volume: 11 Pages: 519-519
  • DOI: 10.3389/fneur.2020.00519
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between executive dysfunction and neuropsychiatric symptoms and impaired instrumental activities of daily living among patients with very mild Alzheimer's disease (2020)
  • Author(s): Ikezaki H, Hashimoto M, Ishikawa T, Fukuhara R, Tanaka H, Yuki S, Kuribayashi K, Hotta M, Koyama A, Ikeda M, Takebayashi M
  • Journal Title: Int J Geriatr Psychiatry Volume: 35 Issue: 8 Pages: 877-887
  • DOI: 10.1002/gps.5308
  • Peer Reviewed
• [Journal Article] Age-Related Changes in Instrumental and Basic Activities of Daily Living Impairment in Older Adults with Very Mild Alzheimer’s Disease. (2020)
  • Author(s): Tabira T, Hotta M, Murata M, Yoshiura K, Han G, Ishikawa T, Koyama A, Ogawa N, Maruta M, Ikeda Y, Mori T, Yoshida T, Hashimoto M, Ikeda M.
  • Journal Title: Dement Geriatr Cogn Disord Extra Volume: 10 Issue: 1 Pages: 27-37
  • DOI: 10.1159/000506281
  • Peer Reviewed / Open Access
• [Journal Article] Thalamic pulvinar metabolism, sleep disturbances, and hallucinations in dementia with Lewy bodies: Positron emission tomography and actigraphy study (2020)
  • Author(s): Kanemoto H, Kazui H, Adachi H, Yoshiyama K, Wada T, Nomura KT, Shimosegawa E, Ikeda M
  • Journal Title: Int J Geriatr Psychiatry Volume: 35 Issue: 8 Pages: 934-943
  • DOI: 10.1002/gps.5315
  • Peer Reviewed
• [Journal Article] Normalized power variance of eLORETA at high-convexity area predicts shunt response in idiopathic normal pressure hydrocephalus (2020)
  • Author(s): Aoki Yasunori、Kazui Hiroaki、Bru?a Ricardo、Pascual-Marqui Roberto D.、Yoshiyama Kenji、Wada Tamiki、Kanemoto Hideki、Suzuki Yukiko、Suehiro Takashi、Matsumoto Takuya、Kakeda Kyosuke、Hata Masahiro、Canuet Leonides、Ishii Ryouhei、Iwase Masao、Ikeda Manabu
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 13054-13054
  • DOI: 10.1038/s41598-020-70035-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Psychogeriatrics in a World with COVID-19 (2020)
  • Author(s): Sano M, Lapid M, Ikeda M, Mateos R, Wang H, Reichman WE
  • Journal Title: Int Psychogeriatr Volume: 32 Issue: 10 Pages: 1101-1105
  • DOI: 10.1017/s104161022000126x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loneliness and social isolation during the COVID-19 pandemic (2020)
  • Author(s): Hwang TJ, Rabheru K, Peisah C, Reichman W, Ikeda M
  • Journal Title: Int Psychogeriatr Volume: 32 Issue: 10 Pages: 1217-1220
  • DOI: 10.1017/s1041610220000988
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The behavioral pattern of patients with frontotemporal dementia during the COVID-19 pandemic (2020)
  • Author(s): Suzuki M, Hotta M, Nagase A, Yamamoto Y, Hirakawa N, Satake Y, Nagata Y, Suehiro T, Kanemoto H, Yoshiyama K, Mori E, Hashimoto M, Ikeda M
  • Journal Title: Int Psychogeriatr Volume: 32 Issue: 10 Pages: 1231-1234
  • DOI: 10.1017/s104161022000109x
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and subtype distribution of early-onset dementia in Japan (2020)
  • Author(s): Awata S, Edahiro A, Arai T, Ikeda M, Takeshi Ikeuchi T, Kawakatsu S, Yoko Konagaya Y, Miyanaga K, Ota H, Suzuki K, Tanimukai S, Utsumi K, Kakuma T
  • Journal Title: Psychogeriatrics Volume: 20 Issue: 6 Pages: 817-823
  • DOI: 10.1111/psyg.12596
  • Peer Reviewed / Open Access
• [Journal Article] The influence of the COVID-19 outbreak on the lifestyle of older patients with dementia or mild cognitive impairment (2020)
  • Author(s): Hashimoto M, Suzuki M, Hotta M, Nagase A, Yamamoto Y, Hirakawa N, Satake Y, Nagata Y, Suehiro T, Kanemoto H, Yoshiyama K, Mori E, Ikeda M
  • Journal Title: Frontiers in psychiatry Volume: 11 Pages: 570580-570580
  • DOI: 10.3389/fpsyt.2020.570580
  • Peer Reviewed / Open Access
• [Journal Article] Renal Function is Associated with Blood Neurofilament Light Chain Level in Older Adults (2020)
  • Author(s): Akamine S, Marutani N, Kanayama D, Gotoh S, Maruyama R, Yanagida K, Sakagami Y, Mori K, Adachi H, Kozawa J, Maeda N, Otsuki M, Matsuoka T, Iwahashi H, Shimomura I, Ikeda M, Kudo T
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 20350-20350
  • DOI: 10.1038/s41598-020-76990-7
  • Peer Reviewed / Open Access
• [Journal Article] The RNA exosome complex degrades expanded hexanucleotide repeat RNA in C9orf72 FTLD/ALS (2020)
  • Author(s): Kawabe Y, Mori K, Yamashita T, Gotoh S, Ikeda M
  • Journal Title: EMBO J Volume: 39 Issue: 19
  • DOI: 10.15252/embj.2019102700
  • Peer Reviewed / Open Access
• [Journal Article] Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders. (2020)
  • Author(s): Ducharme S, Dols A, Laforce R, Devenney E, Kumfor F, van den Stock J, Dallaire-Theroux; C, Seelaar H, Gossink F, Vijverberg E, Huey E, Vandenbulcke M, Masellis M, Trie u C, Onyike C, Caramelli P, de Souza LC, Santillo A Waldo ML, Landin-Romero R, Piguet O, Kelso W, Eratne D, Velakoulis D, Ikeda M, et al.
  • Journal Title: Brain Volume: - Issue: 6 Pages: 1632-1650
  • DOI: 10.1093/brain/awaa018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Primary Progressive Aphasia as a Prodromal State of Dementia With Lewy Bodies: A Case Report. (2020)
  • Author(s): Watanabe H, Ikeda M, Mori E.
  • Journal Title: Front Neurol. Volume: 11:49 Pages: 49-49
  • DOI: 10.3389/fneur.2020.00049
  • Peer Reviewed / Open Access
• [Journal Article] Age-related changes in instrumental and basic activities of daily living impairment in older adults with very mild Alzheimer’s disease. (2020)
  • Author(s): Tabira T, Motta M, Murata M, Yoshimura Y, Han G, Ishikawa T, Koyama A, Ogawa N, Maruta M, Ikeda Y, Mori T, Yoshida T, Hashimoto M, Ikeda M.
  • Journal Title: Dement Geriatr Cogn Dis Extra Volume: -
  • Peer Reviewed
• [Journal Article] 早期診断が早期絶望にならないための認知症診断学 (2020)
  • Author(s): 池田 学
  • Journal Title: 精神科診断学 Volume: 13 Pages: 6-12
• [Journal Article] 前頭側頭葉変性症 (2020)
  • Author(s): 佐竹祐人，佐藤俊介，池田 学
  • Journal Title: CLINICAL NEUROSCIENCE Volume: 38 Pages: 214-218
• [Journal Article] Cerebral Microbleeds are Associated with Cerebral Hypoperfusion in Patients with Alzheimer’s Disease. (2019)
  • Author(s): Hatada H, Hashimoto M, Shiraishi S, Ishikawa T, Fukuhara R, Yuki S, Tanaka H, Miyagawa Y, Kitajima M, Uetani H, Tsunoda N, Koyama A, Ikeda M.
  • Journal Title: J Alzheimers Dis Volume: 71 Issue: 1 Pages: 273-280
  • DOI: 10.3233/jad-190272
  • Peer Reviewed
• [Journal Article] Logopenic progressive aphasia with neologism: a case report. (2019)
  • Author(s): Watanabe H, Ikeda M, Mori E.
  • Journal Title: BMC Neurol. Volume: 19(1) Issue: 1 Pages: 299-299
  • DOI: 10.1186/s12883-019-1524-y
  • Peer Reviewed / Open Access
• [Journal Article] 常同行動に及ぼす意味記憶障害の影響について ―意味性認知症例の行動観察より―. (2019)
  • Author(s): 6.清水秀明，小森憲治郎，豊田康孝，吉田 卓，越智紳一郎，森 崇明，池田 学
  • Journal Title: 神経心理学 Volume: 35 Pages: 225-237
  • NAID: 130007783394
  • Peer Reviewed
• [Journal Article] 地域在住認知症患者に対する生活行為工程分析表（PADA-D）の開発. (2019)
  • Author(s): 田平隆之，堀田 牧，小川敬之，村田美希，吉浦和宏，丸田道雄，池田由里子，石川智久，池田 学.
  • Journal Title: 老年精神医学雑誌 Volume: 30 Pages: 923-931
  • NAID: 40021987316
  • Peer Reviewed
• [Journal Article] 複数の医療施設を経由し，スムーズに福祉施設入所につなげられた前頭側頭型認知症の一例. (2019)
  • Author(s): 佐竹祐人，森 康治，佐藤俊介，繁信和恵，森 悦朗，池田 学
  • Journal Title: 精神科治療学 Volume: 34 Pages: 691-697
  • Peer Reviewed
• [Journal Article] 前頭側頭葉変性症の概念・分類 (2019)
  • Author(s): 佐藤俊介，森 康次，池田 学
  • Journal Title: 老年精神医学雑誌 Volume: 30 Pages: 1073-1079
• [Journal Article] FTLD-Jからみたわが国における前頭側頭型認知症の臨床特徴 (2019)
  • Author(s): 枡田道人，渡辺宏久，勝野雅央，池田 学，祖父江 元
  • Journal Title: 老年精神医学雑誌 Volume: 30 Pages: 1107-1113
• [Presentation] Japanese Frontotemporal Dementia Consortium (2021)
  • Author(s): Manabu Ikeda
  • Organizer: 12th International Conference on Frontotemporal Dementias
• [Presentation] 合同シンポジウム「認知症初期集中支援チームの活動を通して明らかになった独居高齢者の問題と今後の支援策」 (2021)
  • Author(s): 池 田 学
  • Organizer: 第32回日本老年医学会総会
• [Presentation] 特別講演「若年性認知症の現状とケアの方向性」 (2021)
  • Author(s): 池 田 学
  • Organizer: 第22回日本認知症ケア学会大会
• [Presentation] シンポジウム「コロナ禍における認知症初期集中支援チームの活動と精神科医の参画意義」 (2021)
  • Author(s): 池 田 学
  • Organizer: 第117回日本精神神経学会学術集会
• [Presentation] Japanese Frontotemporal Dementia Consortium (2021)
  • Author(s): Ikeda M
  • Organizer: 12th International Conference on Frontotemporal Dementias
  • Int'l Joint Research / Invited
• [Presentation] プレナリーレクチャー「認知症の症候学」 (2020)
  • Author(s): 池田 学
  • Organizer: 第39回日本認知症学会学術集会
• [Presentation] 教育講演「前頭側頭型認知症研究の今後の方向性」 (2020)
  • Author(s): 池田 学
  • Organizer: 第35回日本老年精神医学会
• [Presentation] 若年性認知症の正しい理解と研究の進歩 (2020)
  • Author(s): 池田 学
  • Organizer: 第11回全国若年性認知症フォーラム
  • Invited
• [Presentation] Non AD dementia. Frontotemporal dementia (2019)
  • Author(s): Ikeda M.
  • Organizer: 21th Asia-Pacific Regional Conference of Alzheimer’s Disease International. Kuala Lumpur, Malaysia,
  • Int'l Joint Research / Invited
• [Presentation] The Grobal Action Plan on Public Health Response-APRO. The very young to the oldest. (2019)
  • Author(s): Ikeda M.
  • Organizer: 21th Asia-Pacific Regional Conference of Alzheimer’s Disease International. Kuala Lumpur, Malaysia
  • Int'l Joint Research / Invited
• [Presentation] 認知症と正しく向き合うために―予防と治療の進歩―.「認知症の医療とケア」 (2019)
  • Author(s): 池田 学
  • Organizer: 第30回日本医学会総会2019中部，名古屋
• [Book] 認知障害作業療法ケースブック 重症度別の認知症と作業療法 ADL/IADL能力の獲得に向けて (2021)
  • Author(s): 池田 学（監修）
  • Total Pages: 175
  • Publisher: メジカルビュー社
  • ISBN: 9784758319461
• [Book] 認知症に心理学ができること 医療とケアを向上させるために (2021)
  • Author(s): 池田 学
  • Total Pages: 174
  • Publisher: 誠信書房
• [Book] 神経心理学への誘い 高次脳機能障害の評価 (2020)
  • Author(s): 田川皓一，池田 学
  • Total Pages: 354
  • Publisher: 西村書店
  • ISBN: 9784867060131
• [Book] 「認知症の治療と症状への対応」．かかりつけ医のための認知症マニュアル第2版（日本医師会編） (2020)
  • Author(s): 池田 学
  • Total Pages: 16
  • Publisher: 社会保険研究所
• [Book] 認知障害作業療法ケースブック (2020)
  • Author(s): 池田 学
  • Total Pages: 16
  • Publisher: メジカルビュー社