The impact of argyrophilic grain disease on the development of dementia and its relationship to concurrent Alzheimer's disease-related pathology

Neuropathol Appl Neurobiol. 2005 Jun;31(3):270-9. doi: 10.1111/j.1365-2990.2005.00635.x.


Argyrophilic grain disease (AGD) constitutes a neurodegenerative disorder that occurs in the brains of the elderly and affects 5% of all patients with dementia. Tau protein-containing lesions known as argyrophilic grains and located predominantly in limbic regions of the brain characterize this disease. Dementia is encountered in only a subset of cases that display the morphological pattern of AGD. The aim of this study is to determine the role of concurrent Alzheimer's disease (AD)-related pathology for the development of dementia in AGD patients. A total of 204 post-mortem brains from 30 demented and 49 nondemented AGD patients, 39 AD patients, and from 86 nondemented controls without AGD were staged for AD-related neurofibrillary tangles (NFTs) as well as amyloid beta-protein (Abeta) deposition. To identify differences in AD-related pathology between demented and nondemented AGD cases, and to differentiate the pattern of AD-related changes in demented and nondemented AGD cases from that seen in AD and nondemented controls, we statistically compared the stages of Abeta and NFT distribution among these groups. Using a logistic regression model, we showed that AGD has a significant effect on the development of dementia beyond that attributable to AD-related pathology (P < 0.005). Demented AGD cases showed lower stages of AD-related pathology than did pure AD cases but higher stages than nondemented AGD patients. AGD associated dementia was seen in the presence of NFT (Braak)-stages II-IV and Abeta-phases 2-3, whereas those stages were not associated with dementia in the absence of AGD. In conclusion, AGD is a clinically relevant neurodegenerative entity that significantly contributes to the development of dementia by lowering the threshold for cognitive deficits in the presence of moderate amounts of AD-related pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Brain / pathology*
  • Female
  • Humans
  • Inclusion Bodies / pathology*
  • Logistic Models
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / complications*
  • Neurodegenerative Diseases / pathology
  • Neurofibrillary Tangles / pathology


  • Amyloid beta-Peptides