AbstractINTRODUCTIONAlzheimer's disease (AD) is a heterogeneous disorder characterized by complex underlying neuropathology that is not fully understood. This study aimed to identify cognitive progression subtypes and examine their correlation with clinical outcomes.METHODSParticipants of this study were recruited from the Framingham Heart Study. The Subtype and Stage Inference (SuStaIn) method was used to identify cognitive progression subtypes based on eight cognitive domains.RESULTSThree cognitive progression subtypes were identified, including verbal learning (Subtype 1), abstract reasoning (Subtype 2), and visual memory (Subtype 3). These subtypes represent different domains of cognitive decline during the progression of AD. Significant differences in age of onset among the different subtypes were also observed. A higher SuStaIn stage was significantly associated with increased mortality risk.DISCUSSIONThis study provides a characterization of AD heterogeneity in cognitive progression, emphasizing the importance of developing personalized approaches for risk stratification and intervention.Highlights We used the Subtype and Stage Inference (SuStaIn) method to identify three cognitive progression subtypes. Different subtypes have significant variations in age of onset. Higher stages of progression are associated with increased mortality risk.