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Clinical Manifestations.

Akira Arakawa1, Tomoyasu Matsubara1, Manato Hara1

  • 1Brain Bank for Aging Research, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Tokyo, Japan.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary

Argyrophilic grain disease (AGD) is linked to dementia, particularly at Saito Stage III. Parkinsonism symptoms, including postural instability, may also commonly present in AGD patients.

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Area of Science:

  • Neuropathology
  • Geriatric Medicine
  • Neurodegenerative Diseases

Background:

  • Argyrophilic grain disease (AGD) is an age-related neuropathology characterized by argyrophilic grains and a sequential distribution pattern (Saito stage).
  • Clinical associations of AGD with dementia and parkinsonism remain debated.
  • This study aimed to clarify these associations using a Japanese autopsy cohort.

Purpose of the Study:

  • To investigate the clinicopathological relationship between Argyrophilic grain disease (AGD) and dementia.
  • To determine the association of AGD with parkinsonism.
  • To analyze the impact of Saito stage on dementia severity.

Main Methods:

  • Retrospective analysis of 452 autopsy cases from the Brain Bank for Aging Research (BBAR) cohort (2012-2022).
  • Evaluation of age, Saito stage, and CDR scores in relation to AGD presence.
  • Selection of pure AGD with dementia cases (CDR ≥ 1, Braak stage ≤ 2, BBAR Lewy stage ≤ 1) for detailed clinical feature examination.

Main Results:

  • AGD was present in 50.2% (227/452) of cases, with prevalence and Saito stage increasing with age.
  • AGD-positive cases showed significantly higher rates of dementia (46.7%) and CDR scores (1.2 ± 1.2) compared to AGD-negative cases (27.1%, 0.8 ± 1.2).
  • Saito Stage III cases exhibited the highest dementia rates (77.6%) and CDR scores (1.7 ± 1.0). Six of 20 pure AGD dementia cases presented with parkinsonism.

Conclusions:

  • Argyrophilic grain disease (AGD) is strongly associated with dementia, particularly in advanced Saito stages.
  • Parkinsonism, especially postural instability, is a potential clinical manifestation of AGD.
  • These findings highlight the significant impact of AGD on cognitive and motor function in aging populations.