Healthy brain aging assessed with [¹⁸F]FDG and [¹¹C]UCB-J PET

The average human lifespan has increased dramatically over the past century. However, molecular and physiological alterations of the healthy brain during aging remain incompletely understood. Generalized synaptic restructuring may contribute to healthy aging and the reduced metabolism observed in the aged brain. The aim of this study was to assess healthy brain aging using [¹⁸F]FDG as a measure of cerebral glucose consumption and [¹¹C]UCB-J PET as an indicator of synaptic density.

Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [¹¹C]UCB-J alongside with the fluorodeoxyglucose radioligand [¹⁸F]FDG, we obtained SUVR-1 values for 14 pre-defined volume-of-interest brain regions defined on MRI T1 scans. Regional differences in relative [¹⁸F]FDG and [¹¹C]UCB-J uptake were investigated using a voxel-wise approach. Finally, correlations between [¹¹C]UCB-J, [¹⁸F]FDG PET, and age were examined.

We found widespread cortical reduction of synaptic density in a cohort of older HC subjects (N = 15) compared with young HC subjects (N = 11). However, no reduction persisted after partial volume correction and corrections for multiple comparison. Our study confirms previously reported synaptic stability during aging. Regional differences in relative [¹⁸F]FDG and [¹¹C]UCB-J uptake were observed with up to 20 % higher [¹¹C]UCB-J uptake in the amygdala and temporal lobe and up to 34 % higher glucose metabolism in thalamus, striatum, occipital, parietal and frontal cortex.

In vivo PET using [¹¹C]UCB-J does not support declining synaptic density levels during aging. Thus, loss of synaptic density may be unrelated to aging and does not seem to be a sufficient explanation for the recognized reduction in brain metabolism during aging. Our study also demonstrates that the relationship between glucose consumption and synaptic density is not uniform throughout the human brain with implications for our understanding of neuroenergetics.