Galantamine improves cognitive performance without effecting nicotinic receptors in early Alzheimer's disease as measured by 2[18F]F-A-85380 PET

Abstract

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Objectives: Nicotinic receptors (nAChR) play a crucial role in several cognitive processes. Alzheimer's disease (AD) is characterised by significant cognitive impairment cholinergic dysfunction. Cholinesterase inhibitors can improve cognitive function, however the relationship between these effects and nAChRs are yet to be established in vivo in humans. We examined nAChRs in mild AD before and after chronic galantamine treatment using 2[18F]F-A-85380 PET and also the relationship between nAChR and improvement in cognitive function. Methods: Thirteen drug naive, non-smoking, mild AD patients (MMSE 22±4, aged 77±10 years) were assessed using the Cognitive Drug Research computerised assessment system and measures of global function. Static 20-min PET scans (100-min after injection ~ 200MBq 2[18F]F-A-85380) were acquired before and after 8-weeks of galantamine treatment (16mg/d). A 3-day washout period preceeded the second scan. nAChR density was expressed as Distribution Volume (DV(simplified)). Measures of cognition and DV(simplified) were analysed using t-tests. Results: Patients showed improved performance on global measures of cognition after treatment and on specific measures of attention, verbal fluency and working memory (p<0.05). Treatment did not significantly increase DV(simplified), suggesting stability of nAChRs following galantamine. Furthermore, no significant correlations were found between galantamine-induced changes in cognitive function and DV(simplified). Conclusions: Galantamine treatment in early AD was associated with improvements in cognitive function. Contrary to previous research demonstrating up-regulation of nAChRs with nicotinic agonists this study did not find evidence of nAChR changes with galantamine treatment. The improvement in cognitive function was not correlated with nAChRs, suggesting that changes in nAChR alone may not be responsible for the improvements in cognitive function following galantamine treatment.

Research Support (if any): The Australian Rotary Health Research Fund and Austin Hospital Medical Research Foundation