Argyrophilic grain disease in individuals younger than 75 years: clinical variability in an under‐recognized limbic tauopathy

Abstract

Background Argyrophilic grain disease (AGD) is a limbic‐predominant 4R‐tauopathy. AGD is thought to be an age‐related disorder and is frequently detected as concomitant pathology with other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD. In elderly patients, however, AGD pathology frequently associates with cognitive decline, personality changes, urine incontinence and cachexia. In this study we analysed clinicopathological findings in individuals younger than 75. Methods Patients were identified retrospectively based on neuropathological examinations during 2006 to 2017 and selected when AGD was the primary and dominant pathological finding. Clinical data were obtained retrospectively through medical records. Results We identified 55 patients (2% of all examinations performed during that period) with AGD. In seven cases (13%) AGD was the primary neuropathological diagnosis without significant concomitant pathologies. Two patients were female, median age at the time of death was 64 years (range 51‐74) and the median duration of disease was 3 months (range 0.5‐36). The most frequent symptoms were progressive cognitive decline, urinary incontinence, seizures, and psychiatric symptoms. Brain MRI revealed mild temporal atrophy. Conclusions AGD is a rarely recognized limbic tauopathy in younger individuals. Widening the clinicopathological spectrum of tauopathies may allow identification of further patients who could benefit from tau‐based therapeutic strategies.