The Alzheimer's Prevention Initiative has conducted pilot biomarker studies to characterize and compare age-related changes in preclinical autosomal dominant Alzheimer's disease in the PS1 E280A mutation kindred from Antioquia, Colombia. We previously presented evidence of changes in florbetapir positron emission tomography (PET) 17 years before, cerebrospinal fluid Aβ42 and Tau 14 years before, and hippocampal volume reductions 7 years prior to the median age of MCI onset. We have now completed FDG PET and functional MRI assessments for comparison. Fifty family members from Colombia received FDG PET measurements on a Siemens Biograph mCT 64 PET CT scanner with 30-min dynamic emission scan acquired 30-min after the IV administration of 5mCi of FDG. The cohort included 11 symptomatic carriers: 7 with MCI(46 years +/- 4.5), 4 with AD dementia (51 years +/- 1.9), 19 cognitively normal mutation carriers(33 years +/- 8.0) and 20 non-carriers(NC, 34 years +/- 8.5) between ages 20–56 years old. Regional-to-whole brain cerebral metabolic rates of glucose(CMRgl) were compared between PS1 E280A mutation carriers and NC, accounting for age effects. A nonlinear model was used to characterize CMRgl decline and to estimate the age at which its reductions in mutation carriers became apparent as compared to NC. Voxel-wise comparison of resting state fMRI default mode network (DMN) was performed between carriers and NC using a 10mm spherical posterior cingulate seed region. Compared to non-carriers, symptomatic and pre-symptomatic mutation carriers had significantly lower CMRgl in posterior-cingulate, precuneus, parietal and temporal regions, which was associated with increasing age. Precuneous CMRgl reductions appear to begin approximately 18 years prior to the typical median age of MCI onset, roughly similar to the age at fibrillar amyloid accumulation and CSF Aβ and Tau changes. Compared to non-carriers, symptomatic and pre-symptomatic mutation carriers also had significantly reduced resting state functional connectivity in the DMN. Functional PET and MRI imaging identifies pre-symptomatic brain changes in PS1 E280A carriers. FDG PET reductions are seen near the time of fibrillar amyloid accumulation. These biomarkers provide additional tools for evaluating pre-symptomatic Alzheimer's disease.