Objective: To characterize the natural history of primary progressive aphasia (PPA). Methods: Forty-nine patients (28 women) with newly diagnosed with PPA presenting to a memory disorders clinic between 1992 and 2001 were prospectively evaluated. Results: Median age at onset was 62 years (range 49 to 73 years) and at first visit was 66 years (52 to 80 years). The median duration of follow-up was 4 years (1 to 11 years). Impairments in activities of daily living developed a median of 6 to 7 (2 to 12) years post onset. Seventy-five percent of patients eventually met clinical diagnostic criteria for frontotemporal dementia (FTD), 14%met diagnostic criteria for dementia with Lewy bodies, and 8%developed signs of corticobasal degeneration; 60%of the patients died after a median course of 7 years (3 to 17 years) at a median age of 71 years (56 to 81 years). Patients showing high Mini-Mental State Examination scores, moderate aphasia, and fluent language at first visit subsequently retained greater autonomy in daily life. Conclusions: Although activities of daily living are well maintained during the first years of the disease, patients with primary progressive aphasia (PPA) may lose autonomy 6 to 7 years after onset. The majority of patients with PPA in the current study developed frontotemporal dementia. Objective: To characterize the natural history of primary progressive aphasia (PPA). Methods: Forty-nine patients (28 women) with newly diagnosed with PPA presenting to a memory disorders clinic between 1992 and 2001 were prospectively evaluated. Results: Median age at onset was 62 years (range 49 to 73 years) and at first visit was 66 years (52 to 80 years). The median duration of follow-up was 4 years (1 to 11 years). Impairments in activities of daily living developed a median of 6 to 7 (2 to 12) years post onset. Seventy-five percent of patients eventually met clinical diagnostic criteria for frontotemporal dementia (FTD), 14% of diagnostic criteria for dementia with Lewy bodies, and 8% developed signs of corticobasal degeneration ; 60% of the patients died after a median course of 7 years (3 to 17 years) at a median age of 71 years (56 to 81 years). Patients showing high Mini-Mental State Examination scores, moderate aphasia, and fluent language at first visit subsequently retained g reater autonomy in daily life. Conclusions: Although activities of daily living are well maintained during the first years of the disease, patients with primary progressive aphasia (PPA) may lose autonomy 6 to 7 years later onset. The majority of patients with PPA in the current study developed frontotemporal dementia.