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Apathy Associated with Alzheimer Disease: Use of Dextroamphetamine Challenge

From the Departments of Psychiatry (KLL, NH), Pharmacology and Toxicology (KLL, MR, UEB), Medicine (Neurology) (SEB), Medicine (BAL), and Pharmaceutical Sciences (LSR, UEB), University of Toronto, Toronto, Canada; Neuropsychopharmacology Research Program (KLL, NH, MR, LSR), Regional Geriatric Program of Toronto (BAL), Departments of Psychiatry (KLL, NH), Medicine (Neurology) (SEB), and Geriatric Medicine (BAL), and Neuroscience Research Program (KLL, NH, SEB), Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Preliminary results from this thesis were presented at the 2006 Annual Meeting of the American Psychiatric Association and at the 3rd Annual Canadian Colloquium on Dementia.

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 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, R² = 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.

Key Words: Apathy • Alzheimer disease • dopamine • dextroamphetamine

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