To describe the clinical features, neuropsychological profiles and coexistent pathologies in 21 cases of pathologically confirmed Pick’s disease. 

Pick’s disease is a unique pathologic subtype of frontotemporal lobar degeneration associated with 3 repeat (3R) tau aggregates. Very few studies have examined the clinical variability and disease progression in Pick’s disease due to its rarity.

This study was a retrospective analysis of patients with pathologically confirmed Pick’s disease evaluated at Mayo Clinic Rochester or Jacksonville. Cases were seen between 1995 and 2018 and identified through an existing database.

Twenty-one cases with sufficient clinical data were identified. Behavioral variant FTD (bvFTD) (12/21) was the most common phenotype followed by primary progressive aphasia (PPA) (7/21), corticobasal syndrome (CBS) (1/21) and amnestic dementia (1/21).  Mean age at disease onset was 58 (SD 8.4) years, with PPA cases (µ=51 SD 5.3) presenting earlier than bvFTD (µ=58, SD 5.6). Mean disease duration overall was 11.2 years (SD 3.9) and did not differ significantly between bvFTD (µ=11, SD 2.9) and PPA (µ=11.6, SD 4.5). Age at death was not significantly different in PPA (µ=64, SD 5.2) compared to bvFTD (µ=69, SD 6.5). Half of the cases (n=11/21) demonstrated pure Pick’s disease pathology while some showed co-existent Alzheimer’s disease (n=6), cerebral amyloid angiopathy (n=2), Lewy body disease (n=1) and primary age-related tauopathy (n=1).

In accordance with the literature, our study showed bvFTD and PPA are the most common clinical phenotypes associated with Pick’s pathology, although rare presentations such as CBS were also seen. There was no difference in disease duration between bvFTD and PPA cases. Coexisting non-Pick’s disease pathology was also present in many cases. Our study highlights the clinical and pathologic heterogeneity in Pick’s disease.