Reward System Dysfunction and the Motoric-Cognitive Risk Syndrome in Older Persons

Abstract

During aging, many physiological systems spontaneously change independent of the presence of chronic diseases. The reward system is not an exception and its dysfunction generally includes a reduction in dopamine and glutamate activities and the loss of neurons of the ventral tegmental area (VTA). These impairments are even more pronounced in older persons who have neurodegenerative diseases and/or are affected by cognitive and motoric frailty. All these changes may result in the occurrence of cognitive and motoric frailty and accelerated progression of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. In particular, the loss of neurons in VTA may determine an acceleration of depressive symptoms and cognitive and motor frailty trajectory, producing an increased risk of disability and mortality. Thus, we hypothesize the existence of a loop between reward system dysfunction, depression, and neurodegenerative diseases in older persons. Longitudinal studies are needed to evaluate the determinant role of the reward system in the onset of motoric-cognitive risk syndrome.

Keywords: Alzheimer’s disease; Parkinson’s disease; cognitive and motoric risk syndrome; dopamine; glutamate; older persons; reward system.

Figure 1

The main dopaminergic pathways in the central nervous system.

Figure 2

Hypothetical loop explaining the potential link between age-related changes in rewards system, depression, Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) Dementia.