Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer’s disease
Article first published online: 6 SEP 2006
Psychiatry and Clinical Neurosciences
Volume 60, Issue 5, pages 616–625, October 2006
How to Cite
TROLLOR, J. N., SACHDEV, P. S., HAINDL, W., BRODATY, H., WEN, W. and WALKER, B. M. (2006), Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer’s disease. Psychiatry and Clinical Neurosciences, 60: 616–625. doi: 10.1111/j.1440-1819.2006.01567.x
- Issue published online: 6 SEP 2006
- Article first published online: 6 SEP 2006
- Received 26 December 2005; revised 10 February 2006; accepted 12 March 2006.
- Alzheimer’s disease;
- cholinergic agonist;
- single photon emission computed tomography;
- verbal recognition
Abstract RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer’s disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual’s magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.