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

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Abstract
Argyrophilic grain disease (AGD) constitutes a neurodegenerative disorder that occurs in the brains of the elderly and affects 5% of all patients with dementia. τ 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 β‐protein (Aβ) 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 Aβ 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 Aβ‐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.