.....not much is known about the associations between A? burden, cortical thickness, and cognition in midlife. We examined this question in 109, [cognitively normal] CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as A?+ or A?-. Cortical thickness measurements were derived from the MR images. The A?+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the A?- group. The A?+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early A? aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between A? deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.