Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months

Abstract

Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased AChE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the AChE-R isoform may have a favorable effect on disease stabilization.

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

“…After 12 months of treatment with rivastigmine (mean dose at 12 months, 11.8 mg/d), AChE and BuChE activities decreased from baseline by 46% and 65%, respectively. 21 In comparison, 6 to 12 months of treatment with donepezil or galantamine resulted in increased AChE activity. [18][19][20] The effects of long-term donepezil and rivastigmine administration on ChE activities are depicted in Figure 1.…”

“…10,11 Although all ChE inhibitors share the same basic mode of action (inhibition of AChE), their pharmacokinetic characteristics differ substantially ( Table I). [12][13][14][15][16][17][18][19][20][21][22][23][24] …”

“…These differences occur as a direct result of the underlying pharmacodynamic and pharmacokinetic properties of ChE inhibitors, as outlined in Table I. [12][13][14][15][16][17][18][19][20][21][22][23][24] Safety Drug-Drug Interactions Donepezil and galantamine are both metabolized via the hepatic cytochrome P450 (CYP450) enzyme system. 12 Therefore, caution should be exercised when coprescribing other drugs metabolized via these pathways.…”

“…Inhibition of both ChE enzymes by rivastigmine is sustained during long-term treatment, 21 which is important for the maintenance of ACh levels and thus for clinical efficacy. Although the mechanism behind this long-term effect is as yet unknown, it may be a result of slow dissociation from target enzymes.…”

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

“…46 The BCHE genotype has also been evaluated as a predictor of response to ChEI therapy. Secondary analyses of a randomized controlled trial comparing rivastigmine and donepezil in moderate AD suggested that rivastigmine, a dual acetylcholinesterase and BuChE inhibitor, 47 was associated with improved outcomes compared with donepezil, which inhibits acetylcholinesterase only, in subjects younger than 75 years 48 who did not carry the BCHE-K variant. 49 Another report suggested no difference in response to donepezil or rivastigmine treatment according to BCHE genotype.…”