Dopaminergic enhancement of cognition in old age

As humans age, the brain undergoes many changes. This includes loss of the neurotransmitter dopamine, which forms a bridging link between age and the ensuing changes in cognition. However many questions about the precise nature of this relationship with regards to brain structure and function remain unanswered. These questions are important given our expanding aging population, and the answers may help the discovery of new therapeutic interventions for age-related impairments as well as identify mechanisms to promote successful aging. Old age also provides a model for understanding the role of dopamine in many fundamental human behaviours. The aim of my research was to use a multimodal approach to explore the contribution of dopamine to learning and memory in healthy older age. In this thesis I present four studies in which I used a combination of behavioural testing, pharmacological manipulation, structural and functional magnetic resonance imaging in older adults. I show that dopamine boosts delayed episodic memory in a non-linear dose-dependent manner. Using functional MRI, I show this effect is mediated through consolidation rather than encoding by the hippocampus. In two further imaging studies conducted to explore the role of dopamine in reward-based learning, I show that the flexibility of learning depends on the structural integrity of the substantia nigra/ventral tegmental area (the origin of dopamine projections) and that pharmacological enhancement of dopamine levels can remediate abnormal reward processing in the ventral striatum. Individual differences in neural activity associated with reward prediction also relate to anatomical nigro-striatal connectivity, identified using diffusion tensor imaging. Finally, I show that in old age, valence influences decision-making in relation to ones own beliefs about the future, mediated by volume of the anterior cingulate cortex. I conclude this thesis with a brief discussion of the implications of these findings, study limitations and potential future studies.