Journal of Alzheimer's Disease - Volume 11, issue 4

Authors: Coyle, Joseph T. | Geerts, Hugo | Sorra, Karin | Amatniek, Joan

Article Type: Research Article

Abstract: Galantamine is an approved treatment for mild to moderate Alzheimer's disease, with demonstrated benefits for cognition and functional ability in human studies. The mechanism of action that is most generally recognized as underlying the clinical benefits of galantamine is inhibition of brain acetylcholinesterase (AChE). However, an increasing body of evidence suggests that an additional mechanism, most likely allosteric modulation of nicotinic acetylcholine receptors (nAChRs), may contribute to the therapeutic effects of galantamine. This review summarizes the research on this additional mechanism, with emphasis on data derived from in vivo animal studies and open-label hypothesis-generating studies in humans. In general, these …studies provide evidence of effects beyond those of AChE inhibition alone, most notably in comparisons with other AChE inhibitors, in which galantamine produced similar or greater effects at doses that provided lower levels of brain AChE inhibition. The use of nAChR agonists and antagonists in some of these studies lends support to the proposed allosteric potentiating ligand activity of galantamine at nAChRs. This dual action of galantamine may account for its therapeutic profile. Show more

Keywords: Galantamine, donepezil, nicotinic acetylcholine receptors, Alzheimer's disease, allosteric potentiation, acetylcholinesterase inhibition

DOI: 10.3233/JAD-2007-11411

Citation: Journal of Alzheimer's Disease, vol. 11, no. 4, pp. 491-507, 2007

Authors: Emre, Murat | Cummings, Jeffrey L. | Lane, Roger M.

Article Type: Research Article

Abstract: Parkinson's disease dementia (PDD) and Alzheimer's disease (AD) are both characterized by cognitive abnormalities, neuropsychiatric symptoms, and cholinergic deficits. We reviewed data from large, placebo-controlled clinical trials conducted with rivastigmine in patients with PDD and AD to evaluate similarities and differences in response to treatment. In placebo groups, AD patients appeared to show more rapid cognitive decline than those with PDD. Treatment effects (rivastigmine versus placebo) on cognitive performance over 6 months were quantitatively similar in both populations, but qualitatively different: in AD, cognitive abilities were stabilized by rivastigmine compared to declines in placebo groups, whereas in PDD symptomatic improvements …above baseline drove treatment effects while placebo patients had limited change. On activities of daily living, stabilization (rather than improvement) was observed in both dementia types. A more aggressive course of placebo decline, and greater treatment differences (rivastigmine versus placebo), were seen in sub-populations of both PDD and AD patients with hallucinations at baseline. The safety and adverse event profiles were comparable in the two populations. In conclusion, the magnitude of effect with rivastigmine versus placebo is quantitatively comparable in patients with AD and PD, but the treatment effect tended to be one of stabilization in AD, while in PDD improvements over baseline were seen. In both populations, hallucinations may identify patients who are likely to be more treatment-responsive. Show more

Keywords: Alzheimer's disease, cholinesterase inhibitors, parkinson's disease dementia, rivastigmine

DOI: 10.3233/JAD-2007-11412

Citation: Journal of Alzheimer's Disease, vol. 11, no. 4, pp. 509-519, 2007

Article Type: Announcement

DOI: 10.3233/JAD-2007-11413

Citation: Journal of Alzheimer's Disease, vol. 11, no. 4, pp. 521-523, 2007