Apathy Associated with Alzheimer Disease: Use of Dextroamphetamine Challenge

Objective: To assess the role of the dopaminergic brain reward system (BRS) in apathy associated with Alzheimer disease (AD).

Design: BRS function was probed in 20 AD patients using dextroamphetamine (d-amph) challenge. After baseline behavioral testing, patients were given a single 10 mg dose of d-amph. The time course of the subjective response to d-amph was assessed at hourly intervals for 4 hours.

Setting: Three outpatient dementia clinics associated with a university-affiliated hospital.

Participants: Twenty AD patients aged 77 +/- 8 years with Neuropsychiatric Inventory (NPI) apathy scores of 3.4 +/- 3.5 and Mini-Mental State Examination scores of 20.4 +/- 5.1.

Measurements: Patients were classified as apathetic based on an NPI apathy subscore of > or =4. Apathy severity was assessed using the Apathy Evaluation Scale (AES). The subjective and behavioral responses to d-amph were assessed using computerized versions of the Addiction Research Centre Inventory (ARCI), Profile of Mood States and Connor's Continuous Performance Task.

Results: Repeated measures ANOVA revealed a significant interaction between the presence of apathy and the peak subjective response to d-amph on the ARCI, such that while nonapathetic AD patients were responsive to the rewarding effects of d-amph, apathetic patients were not (F(1,17) = 4.93, p = 0.04). Continuous AES scores were predicted by peak ARCI positive effects scores and baseline overall behavioral disturbances (NPI total) in a backward linear regression analysis using the entire study sample (F(2,17) = 10.00, p = 0.01, R(2) = 0.49).

Conclusions: Apathy in AD is associated with a blunted subjective response to d-amph, which may be indicative of dysfunction in the BRS.