No Effect of Donepezil on Striatal Dopamine Release in Mild to Moderate Alzheimer's Disease

Suzanne Reeves (1) , Richard Brown (1) , David Matthews (2) , Robert Howard (1) , Paul Grasby (3)

1 Institute of Psychiatry
2 Croydon Memory Service
3 Imperial College London

Objective: Work in experimental animals suggests that an interaction with dopaminergic networks might explain some of the therapeutic effects of the cholinesterase inhibitor class of drugs. This study aimed to test whether acute (single 5mg) or four to eight weeks (5 to 10mg) treatment with oral donepezil would elicit measurable striatal dopamine (DA) release in patients with mild to moderate Alzheimer's Disease (AD). A second aim was to establish whether any increase in DA levels would be associated with improvements in cognitive and motor function. Methods: Percentage change in [11C] Raclopride (RAC) binding potential (BPND) between baseline and treatment conditions was used to provide a measure of DA release. Repeated measures ANOVA was used to determine the effect of treatment upon [11C] RAC BPND and neuropsychological test performance. Results: Contrary to our prediction there was no significant change in [11C] RAC BPND after acute or a mean of six weeks (range = 4-12) treatment with donepezil. Although motor speed (finger tapping) improved following 4-12 weeks treatment with donepezil (F1,19 = 8.7, p = 0.009) this was not associated with the degree of change in [11C] RAC BPND. Conclusions: Our findings provide no evidence that striatal DA levels are altered during the first 3 months of donepezil treatment. However we cannot rule out the possibility that extrastriatal effects may be occurring.

Mots clés: PHARMACOLOGY; ALZHEIMER'S DISEASE; COGNITION; NEUROCHEMISTRY; PET; LIGAND STUDIES

Suzanne Reeves, Richard Brown, David Matthews, Robert Howard, Paul Grasby. No Effect of Donepezil on Striatal Dopamine Release in Mild to Moderate Alzheimer's Disease. Journal of Neurology, Neurosurgery and Psychiatry, 2009, 81 (1), pp.119. ⟨10.1136/jnnp.2009.172510⟩. ⟨hal-00552767⟩