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).


METHODS
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.


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


METHODS
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.


METHODS
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.
Lanctôt
Krista L
KL
Department of Psychiatry, University of Toronto, Toronto, Canada. krista.lanctot@sunnybrook.ca
Herrmann
Nathan
N
Black
Sandra E
SE
Ryan
Michelle
M
Rothenburg
Lana S
LS
Liu
Barbara A
BA
Busto
Usoa E
UE
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology*; D000704:Analysis of Variance; D001526:Behavioral Symptoms / Q000188:drug therapy / Q000503:physiopathology*; D003913:Dextroamphetamine / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male
D018765:Dopamine Uptake Inhibitors; D003913:Dextroamphetamine; D004298:Dopamine