Argyrophilic grain disease: epidemiology and association with cognitive decline and parkinsonism

Abstract Argyrophilic grain disease is an age-related disorder characterized by the presence of argyrophilic grains. Argyrophilic grain disease has a sequential distribution pattern that begins in the ambient gyrus (Saito Stage I), spreads to the medial temporal lobe (Saito Stage II) and reaches the basal forebrain and cingulate gyrus (Saito Stage III). A strong association with cognitive decline, especially in cases of Saito Stage III argyrophilic grain disease, has also been reported. The main clinical feature includes cognitive decline characterized by memory disturbance, although conflicting results have been reported. Recent studies suggest an association with parkinsonism. To clarify the association between argyrophilic grain disease, cognitive decline and parkinsonism, we performed a clinicopathological study using the Brain Bank for Aging Research autopsy cohort in Japan. Approximately half (227) of the 452 consecutive autopsy cases had argyrophilic grain disease, and the frequency and stage of argyrophilic grain disease increased with age. Among the argyrophilic grain disease cases, 20 were demented without any comorbid pathology responsible for it, a condition referred to as dementia with grains. Furthermore, 6 of the 20 dementia with grains cases presented with parkinsonism, particularly postural instability, in addition to memory disturbance. Dementia with grains cases with parkinsonism had significantly more argyrophilic grains in the substantia nigra than those without parkinsonism and showed significantly decreased anti-dopamine transporter immunoreactivity in the putamen compared to control cases. Given these findings, argyrophilic grain disease is strongly associated with cognitive decline, especially in Saito Stage III cases, and parkinsonism is a new common clinical presentation. The extension of argyrophilic grain disease pathology to the nigrostriatal system may contribute to the development of parkinsonism.