Dedifferentiation of caudate-cortical connectivity is linked to reduced D1 dopamine receptor availability and poorer memory function in aging

Decreasing integrity of striato-cortical circuits has been highlighted as an important determinant of declines in flexible, higher-order cognition in older age. Here, leveraging multi-modal (fMRI, PET) neuroimaging data from a large adult lifespan sample, we demonstrate older age to be associated with less specific functional coupling between the caudate and cortical association networks. This age-related dedifferentiation of caudate- cortical connectivity was present during both rest and an active working memory task, and predicted poorer short and long-term memory performance with older age. Notably, reduced striatal and prefrontal dopamine D1-like receptor (D1DR) availability was associated with less specific caudate-cortical coupling across the lifespan and accounted for age-related variation in this measure. These findings highlight decreased dopaminergic neuromodulation as one factor contributing to differences in striato-cortical function, and memory performance, with older age.