Cited by 7Dementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatments

Distinct early symptoms in neuropathologically proven frontotemporal lobar degeneration

Kawakami, Ito, Arai, Tetsuaki, Shinagawa, Shunichiro, Niizato, Kazuhiro, Oshima, Kenichi, Ikeda, Manabu·2021·International Journal of Geriatric Psychiatry

Abstract

Objectives: Frontotemporal lobar degeneration (FTLD) is associated with accumulation of neurodegeneration‐related protein, such as tau, TAR DNA‐binding protein 43 (TDP‐43), or fused in sarcoma protein (FUS). There have been very few systematic studies of the early symptoms of clinical phenotypes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA). Clinical subtypes and the patterns of atrophy reflect protein‐accumulation patterns, but the relationship between early symptoms and pathological findings remains unclear. Methods: We retrospectively investigated the clinical records and examined the neuropathology of 39 bvFTD and 6 svPPA patients to identify symptoms appearing within 2 years of the first clinically apparent changes. Results: The bvFTD group consisted of 13 FTLD‐tau, 18 FTLD‐TDP, and 8 FTLD‐FUS, and the svPPA group consisted of 6 FTLD‐TDP. Age at death is significantly younger in FTLD‐FUS (52.8 ± 12.6; P = 0.0104 < 0.05). Over 50% of bvFTD patients show apathy or inertia, and distinct language features appear early in svPPA. Interestingly, bvFTD and svPPA frequently present additional symptoms, not included in the diagnostic criteria, such as physical signs, reticence, dazed condition, and delusions. Stereotyped behaviors, hyperorality and dietary changes are prominent in FTLD‐FUS, while linguistic deficits are greater in FTLD‐TDP. Conclusions: Specific symptoms tend to appear in the early stage of FTLD in each pathological background. They might reflect the morphological features and pathological progression, and should be helpful in the stratification of patients for future therapeutic trials based on the proteinopathies.

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Crossref · 10.1002/gps.5387

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Authors
Kawakami, I., Arai, T., Shinagawa, S., Niizato, K., Oshima, K., & Ikeda, M.
Affiliations
  • Tokyo Metropolitan Matsuzawa Hospital (JP)
  • University of Tsukuba (JP)
  • Jikei University School of Medicine (JP)
  • The University of Osaka (JP)
Corresponding author
Kawakami, Ito
Venue
International Journal of Geriatric Psychiatry
Publisher
Wiley
Published
2020-08-26
Volume
36
Issue
1
Pages
38-45
ISSN
  • 0885-6230 (ISSN-L)
  • 1099-1166
OpenAlex
W3047179533
Cited by
7
References
43
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1
FWCI
0.73
Type
journal article
Language
en
Open access
closed
Locations
  • International Journal of Geriatric Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Japan Agency for Medical Research and Development (JP18dm0908001)
  • Naito Foundation (Naito Foundation Subsidy for Female Researchers)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
frontotemporal lobar degeneration, behavioral variant frontotemporal dementia, semantic dementia, FTLD-tau, FTLD-TDP, early symptoms, apathy, stereotypy, hyperorality, language deficits, delusions, reticence, proteinopathies, age at death
MeSH terms
DNA-Binding Proteins, Humans, Phenotype, Retrospective Studies, tau Proteins, RNA-Binding Protein FUS, Frontotemporal Lobar Degeneration, Frontotemporal Dementia

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