| Title : Cholinesterase inhibition: is there evidence for disease-modifying effects? - Shanks_2009_Curr.Med.Res.Opin_25_2439 |
| Author(s) : Shanks M , Kivipelto M , Bullock R , Lane R |
| Ref : Curr Med Res Opin , 25 :2439 , 2009 |
| Abstract : BACKGROUND: Cholinesterase inhibitors are broadly established as first-line symptomatic therapy for Alzheimer's disease (AD). Symptomatic effects are mediated by the inhibition of acetyl- and/or butyryl-cholinesterase (AChE and/or BuChE) - the enzymes that degrade acetylcholine (ACh) in the synapse. However, ACh is also found outside the synapse ('extracellular ACh') where, among other activities, it plays a role in controlling inflammation and might impact on pathological changes. OBJECTIVE/SCOPE: New data and clinical findings are reviewed and discussed to build a preliminary case for possible disease-modifying effects of cholinesterase inhibition. FINDINGS: Trials seeking to demonstrate disease-modifying effects in subjects with mild cognitive impairment failed to reach their primary endpoints, but these failures might relate to aspects of trial methods and analyses. A re-analysis of one of these trials, using a more sensitive model controlling for factors that predict progression to AD, showed a significant delay in progression to AD with dual cholinesterase inhibition over 3 to 4 years. Taken with other evidence, it is plausible that cholinesterase inhibition might contribute to disease modification. The detection of putative disease-modifying effects may be most easily implemented in certain patient subpopulations, and genotyping studies suggest a particular role for BuChE. CONCLUSION: Long-term inhibition of BuChE might be especially important when exploring any disease-modifying effects of cholinesterase inhibitors. Elucidation of the mechanisms involved could provide insights leading to the development of new treatments that modify the development and progression of AD. |
| ESTHER : Shanks_2009_Curr.Med.Res.Opin_25_2439 |
| PubMedSearch : Shanks_2009_Curr.Med.Res.Opin_25_2439 |
| PubMedID: 19678754 |
Shanks M, Kivipelto M, Bullock R, Lane R (2009)
Cholinesterase inhibition: is there evidence for disease-modifying effects?
Curr Med Res Opin
25 :2439
Shanks M, Kivipelto M, Bullock R, Lane R (2009)
Curr Med Res Opin
25 :2439