Since Down syndrome (DS) is associated with amyloid β (Aβ) deposition, we characterized imaging measurements of regional fibrillar Aβ burden, cerebral metabolic rate (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD+), 12 DS without dementia (DS/AD-), and 9 normal controls (NCs).There were significant group differences in mean SUVRs for florbetapir with DS/AD+ having the highest, followed by DS/AD-, followed by NC. For FDG-PET, posterior cingulate rCMRgl in DS/AD+ was significantly reduced compared to DS/AD- and NC. For vMRI, hippocampal volumes were significantly reduced for the DS/AD+ compared to DS/AD- and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Aβ, rCMRgl, and l rGMV alterations in the dementia stage and prior to the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS.