title: Antioxidant enzymatic activities in Alzheimer's disease: the relationship to acetylcholinesterase inhibitors.
abstract: The mode of action of acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD) is mainly by potentiating neuronal transmission. Animal studies have also consistently described a role for AChEIs in enhancement of antioxidants and attenuation of oxidative stress. The influence of AChEIs on blood antioxidants in AD patients has not been established before. Furthermore, AChEI treatment, or lack of it, may have contributed to the inconsistent antioxidant data reported by other studies so far. Here we sought to investigate the potential modulation effect of AChEIs on blood antioxidants in AD patients. Catalase (CAT) and glutathione reductase (GR) activities were analyzed in 25 drug naïve patients (Group A), 43 patients receiving AChEIs (Group B) and 34 cognitively unimpaired controls (Group C). A statistically significant difference for CAT and GR was observed between the two AD groups (A and B) when compared to the control group C (KW-H = 36.530, p < 0.001; post hoc tests p < 0.001 and KW-H = 37.814, p < 0.001; post hoc tests p < 0.001, respectively). In contrast, CAT and GR activities did not differ significantly between the two AD groups, and were not influenced by AChEI treatment. Hence, these results do not replicate the extensively reported data from animal studies and question whether AChEI efficacy in AD is mediated by processes beyond neuron to neuron enhancement of transmission. Studies assessing a wider range of oxidative/inflammatory markers taking into account type, dosage, and treatment duration of the various acetylcholinesterase inhibitors are now needed.
authors.affiliation: Cognitive Treatment and Research Unit, Sussex Partnership NHS Foundation Trust, East Sussex, UK. Anthony.Klugman@sussexpartnership.nhs.uk
authors.forename: Anthony
authors.initials: A
authors.lastname: Klugman
authors.forename: Declan P
authors.initials: DP
authors.lastname: Naughton
authors.forename: Mokhtar
authors.initials: M
authors.lastname: Isaac
authors.forename: Iltaf
authors.initials: I
authors.lastname: Shah
authors.forename: Andrea
authors.initials: A
authors.lastname: Petroczi
authors.forename: Naji
authors.initials: N
authors.lastname: Tabet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D002374:Catalase / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D005702:Galantamine / Q000494:pharmacology / Q000627:therapeutic use; D005980:Glutathione Reductase / Q000097:blood*; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D048448:Phenylcarbamates / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D000068836:Rivastigmine
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D002374:Catalase; D005980:Glutathione Reductase; D000068836:Rivastigmine