Unlocking the Dynamics of Dopamine in Aging: Balancing Pre- and Post-Synaptic Mechanisms for Optimal Brain Function across the Adult Lifespan

Many older adults experience impairment of cognitive functions, such as memory.

While changes in the aging brain are often assumed to underlie cognitive decline, it is surprisingly hard to identify coupled brain-cognitive changes in aging.

This challenge is magnified in the search for modifiable brain alterations that could serve as targets for various kinds of intervention.

Promising candidates are age-related alterations in neurotransmitters like dopamine (DA) and noradrenaline (NA), which are crucial for brain functions.

Yet, existing aging models of DA and NA are inadequate, as past studies solely focused on either the DA or NA system and merely emphasize a single aspect of the multifaceted DA system (either pre- or post-synaptic).

This represents a serious omission because various parts of the DA system are tightly regulated and the balance between pre- and post-synaptic markers, rather than each marker in isolation, are critical for efficient neuromodulatory function.

The overarching goal of this research program is to address the fundamental question of how the dynamic interplay between pre- and post-synaptic markers of the DA, along with its interaction with NA, evolves as individuals age and how these dynamics are linked to neurocognitive decline.

Of particular interest is whether transiently restoring the balance between components of the DA/NA systems through pharmacological intervention, opens a window to remodel the aging brain and improve cognitive function.