Longitudinal relationships between Aβ and tau to executive function and memory in cognitively normal older adults.

The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an "Aβ-executive function, tau-memory" double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau.