Becker JA, Gidicsin C, Maye J, Pepin L, Sperling R, Johnson K.
Amyloid-Modulated Age-Related Changes in FDG Metabolism in Normal and Mildly Impaired Elderly.Human Amyloid Imaging Abstract.
2012 Jan 1;
An increase in cerebral amyloid-beta (Ab) accumulation has been postulated as one of the initiating events in Alzheimer’s disease that leads to a cascade of sequelae including neurodegeneration and declining glucose metabolism.
Objective: To evaluate the association of cerebral amyloidosis with longitudinal change in FDG metabolism in cognitively normal (CN; CDR=0) older individuals and individuals with MCI (CDR=0.5).
One hundred-five CN and66 MCI subjects with known amyloid status and at least two FDG PET time-points available (mean acquisition interval ~2.5yr) were identified in the ADNI1 and Harvard Aging Brain Study samples (68 Ab- and7 Ab+ CNs/120 MCIs). FDG and PiB volumes were spatially normalized using SPM8, resampled in AAL regions, and scaled to pons (FDG) or cerebellum (PIB). FDG change was modeled in CN and MCI groups separately as a function of baseline age, time since baseline, amyloid status (Ab+/-) and Ab-by-time interaction using mixed-effect regression.
Significant within-subject FDG decline with age was identified in Ab- CNs most prominently in the anterior and posterior cingulate (p<0.02), superior temporal pole (p<10^-4) and hippocampus (p<0.005). Ab+ CNs exhibited no regions with significantly different baseline FDG or with significantly different rates of within-subject FDG decline compared to Ab- subjects. Among Ab- MCIs, within-subject decline of metabolism with age remained significant in the hippocampus (p<10^-3), posterior cingulate (p<0.03) and superior temporal pole (p<10^-4), while Ab+ MCIs exhibited significantly decreased baseline metabolism globally (p<10^-3), and specifically in the inferior parietal and lateral temporal cortices, and in the precuneus/posterior cingulate (p<10^-3). Ab+ MCIs had significantly greater rates of decline in hippocampus (p<0.02), inferior temporal (p<0.04), and posterior cingulate (p<0.02).
These results suggest that dynamics of FDG metabolism differ by clinical stage, such that MCI subjects exhibit steeper within-subject declines than CN subjects. We were not able to demonstrate with regional data steeper FDG declines in Ab+ vs Ab- CNs.