Amyloid burden, brain metabolism, and gray matter volume in SuperAgers

Abstract SuperAgers (SA) are adults aged ≥ 80 years with memory equivalent to individuals 20 to 30 years younger. Few studies have evaluated multimodal neuroimaging approach in the same SA cohort. To investigate neurobiological mechanisms underlying exceptional cognitive aging by evaluating cortical amyloid deposition, regional cerebral glucose metabolism (rBGM), and gray matter volume (GMV), and their associations with neuropsychological performance and subjective cognitive decline (SCD). The participants were classified as SA (n = 11), age-matched healthy controls (HC80; n = 23), and healthy controls aged 60 to 69 years (HC60; n = 23). Positron-emission tomography (PET) using 11C-PIB and 18F-FDG were analyzed using semiquantitative three-dimensional stereotactic surface projection (3D-SSP), with group comparisons using Statistical Parametric Mapping 8 (SPM8). The median ages were 81 years (interquartile range [IQR] = 5.0) for SA, 83 years (IQR = 5.0) for HC80, and 66 years (IQR = 3.0) for HC60. All groups had a median of 16 years of schooling (IQR for SA = 7, for HC80 and HC60 = 5). There were 4 PIB-PET positive individuals (36.4%) in the SA group, which is similar to the HC80 group (40.9%). Also, 6 SA had SCD, with 3 being PIB-positive. In SA, composite SUVr predicted RAVLT delayed recall (β = −0.666, p = 0.011, adjusted R2 = 0.748), controlling for age, sex, and schooling. Compared to HC80, the SA group showed increased metabolism in the anterior cingulate gyrus and caudate, as well as increased GMV in the putamen. The SA group exhibited similar amyloid burden to HC80, yet amyloid deposition specifically impaired their memory. Increased rBGM and GMV in the salience network and striatum suggest these regions support successful cognitive aging.