Developing early vulnerable area aggregates for PET detection of beta‐amyloid based on young and middle‐aged adults from the Framingham Heart Study

Background As Alzheimer’s clinical trials shift earlier and earlier in the disease process, current global PET measures of beta‐amyloid (Aβ) positivity may be insufficient for detecting the earliest Aβ deposits. Regional PET measures may better detect the earliest deposits. Previous efforts to identify early‐accumulating regions have inferred which regions may be most vulnerable based on older adults. Our aim was to identify early vulnerable areas by looking earlier in the lifespan. Method 235 clinically‐normal adults ages 33‐74 from the Framingham Heart Study (FHS) underwent one time‐point of dynamic Pittsburgh Compound B (PIB) PET (Tab.1). PIB was regionally quantified in Desikan regions using distribution volume ratio (DVR, cerebellar reference). Linear and quadratic (Age + Age2) models were run to determine association of age with region of interest (ROI) PIB DVR, and ROIs with significantly increasing DVRs were selected for the generation of candidate early vulnerable area (EVA) aggregates. Multiple aggregate EVA DVRs (EVA2‐EVA11) were generated by sequential addition of regions in rank order of descending Age2 estimate. EVA positivity was derived from both full‐sample GMM and