The Role of the Dopaminergic Brain Reward System in Apathy Associated With Alzheimer's Disease

Apathy, or lack of motivation, affects up to 80% of Alzheimer's disease (AD) patients. These amotivational symptoms increase patient reliance on caregivers, increase caregiver burden and distress, and increase the risk of patient institutionalization. Only 50% of patients with apathy respond to current treatment with cholinesterase inhibitors. The mechanism of apathy in AD is unknown hampering rational treatment. Our proposed pilot study will provide initial data required to develop an amphetamine challenge paradigm to probe the brain reward system. These results will be used to develop a larger study evaluating the role of the brain reward system in apathy in AD and link this information with pharmacologic treatment. AD is a complex neurobiological illness that needs to be understood at several levels to optimize treatment. At a neurochemical level, one has to identify the neurotransmitter abnormalities that accompany the clinical symptoms. The neurochemical level of analysis provides the link between pathology and symptoms and, for now, is the only avenue for biological therapies. Next, one has to translate knowledge of neurochemical abnormalities to practical treatments for the symptoms of AD. This pilot will allow us to develop a study that can address both of these goals. Furthermore, the larger study will further define the emerging concept of apathy as a syndrome and has broader implications for apathy in many other neuropsychiatric diseases.