The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance

Researchers have identified changes in dopaminergic neuromodulation as playing a key role in adult memory decline. Facilitated by technical advancements, recent research has also implicated noradrenergic neuromodulation in shaping late-life memory performance. However, it is not yet clear whether these two neuromodulators have distinct roles in age-related cognitive changes. Combining longitudinal high-resolution magnetic resonance imaging of the dopaminergic substantia nigra–ventral tegmental area (SN–VTA) and the noradrenergic locus coeruleus (LC) in younger (n = 69) and older adults’ (n = 251), we found that dopaminergic and noradrenergic integrity are differentially associated with individual differences in memory performance. While LC integrity was related to better episodic memory across several memory tasks, SN–VTA integrity was linked to working memory. Moreover, consistent with their dense interconnection and a largely shared biosynthesis, dopaminergic and noradrenergic brain regions’ integrity were positively related, and correlated with medial temporal lobe volumes. Longitudinally, we found that older age was associated with more-negative change in SN– VTA and LC integrity (time point 1–time point 2; mean delay ∼1.9 years). Importantly, changes in LC integrity reliably predicted future episodic memory performance (at time point 3). These findings support the feasibility of in-vivo indices for catecholaminergic integrity with potential clinical utility, given the degeneration of both neuromodulatory systems in several age-associated diseases. Moreover, they highlight differential roles of dopaminergic and noradrenergic neuromodulatory nuclei in late-life cognitive decline.