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No effect of donepezil on striatal dopamine release in mild to moderate Alzheimer’s disease
  1. S Reeves1,
  2. R Brown1,
  3. D Matthews2,
  4. R Howard1,
  5. P Grasby3
  1. 1
    MRC Centre for Neurodegeneration Research, King’s College London, Institute of Psychiatry, London, UK
  2. 2
    Croydon Memory Service, South London and Maudsley NHS Trust, London, UK
  3. 3
    MRC Clinical Science Centre, Imperial College, Hammersmith Hospital, London, UK
  1. Correspondence to Dr S Reeves, Section of Old Age Psychiatry, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, De Crespigny Park, Camberwell, London SE5 8AF, UK; s.reeves{at}iop.kcl.ac.uk

Abstract

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 5 mg) or 4–8 weeks (5–10 mg) of treatment with oral donepezil would elicit measurable striatal dopamine (DA) release in patients with mild to moderate Alzheimer’s disease. 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 on [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 6 weeks (range 4–12) of treatment with donepezil. Although motor speed (finger tapping) improved following 4–12 weeks of 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.

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Footnotes

  • Funding Wellcome Research Trust, Medical Research Council and NIHR Biomedical Research Centre.

  • Competing interests RH has received honoraria as speaker’s fee from Lundbeck and Pfizer-Eisai. Pfizer-Eisai and Lundbeck have provided medication and placebo for independently funded randomised controlled trials on which RH is Chief Investigator. PG has served as an occasional consultant to GlaxoSmithKline, Merck and Pfizer.

  • Ethics approval The study was approved by the Charing Cross and the Joint South London and Maudsley and Institute of Psychiatry NHS Research Ethics Committees. ARSAC (the Administration of Radioactive Substances Advisory Committee) granted permission to administer [11C]-raclopride

  • Provenance and Peer review Not commissioned; externally peer reviewed.

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