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

J. R. Ellis, P. J. Nathan, V. L. Villemagne, R. S. Mulligan, T. Saunder, K. Young, C. L. Smith, J. Welch, M. Woodward, K. A. Wesnes, G. Savage, C. C. Rowe

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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 (DV S). 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.

    Original languageEnglish
    Pages (from-to)79-91
    Number of pages13
    JournalPsychopharmacology
    Volume202
    Issue number1-3
    DOIs
    Publication statusPublished - Jan 2009

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