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Galantamine-induced improvements in cognitive function are not related to alterations in α4β2 nicotinic receptors in early Alzheimer’s disease as measured in vivo by 2-[18F]Fluoro-A-85380 PET

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Abstract

Introduction

The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer’s disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo.

Materials and methods

2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of ∼200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DVS).

Results

Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DVS before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DVS, suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.

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Acknowledgements

Research support was provided by the Austin Hospital Medical Research Fund. Fellowship support for JRE was provided by the Australian Rotary Health Fund and the Monash University Postgraduate Publication Award scheme. Fellowship support for PJN was provided by the National Health and Medical Research Council of Australia and the Alzheimer’s Australia Research Foundation. The authors would like to thank Drs. Michel Bottlaender and Frédéric Dollé of the SHFJ PET Center, Orsay (France) for provision of precursor and technical assistance.

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Authors and Affiliations

  1. School of Psychology, Psychiatry, and Psychological Medicine, Monash University, Melbourne, Victoria, Australia

    J. R. Ellis, P. J. Nathan & G. Savage

  2. Department of Nuclear Medicine and Center for PET, Austin Health, Melbourne, Victoria, Australia

    J. R. Ellis, V. L. Villemagne, R. S. Mulligan, T. Saunder, K. Young, C. L. Smith, J. Welch & C. C. Rowe

  3. Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK

    P. J. Nathan

  4. Department of Aged Care, Austin Health, Melbourne, Victoria, Australia

    M. Woodward

  5. Cognitive Drug Research Ltd., Goring-on-Thames, UK

    K. A. Wesnes

  6. Macquarie Centre for Cognitive Science, Macquarie University, Sydney, New South Wales, Australia

    G. Savage

  7. Department of Nuclear Medicine, Austin Hospital, 145 Studley Rd, Heidelberg, Melbourne, Victoria, 3084, Australia

    J. R. Ellis

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  1. J. R. Ellis
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Correspondence to J. R. Ellis.

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Ellis, J.R., Nathan, P.J., Villemagne, V.L. et al. Galantamine-induced improvements in cognitive function are not related to alterations in α4β2 nicotinic receptors in early Alzheimer’s disease as measured in vivo by 2-[18F]Fluoro-A-85380 PET. Psychopharmacology 202, 79–91 (2009). https://doi.org/10.1007/s00213-008-1347-9

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  • DOI: https://doi.org/10.1007/s00213-008-1347-9

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