title: Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease.
abstract: BACKGROUND
  Many factors could be responsible for the different response to treatment with the cholinesterase inhibitors (ChEIs) donepezil and rivastigmine in Alzheimer's disease (AD) patients. Sex and the variants of the estrogen receptor α (ESR1) gene are reported to modulate AD susceptibility or the course of the disease. The aim of the present study was to verify whether patient's sex and ESR1 genotype could influence the response to ChEI treatment, as there is evidence that estrogens affect cholinergic system functioning.
  
  
  METHODS
  Two ESR1 intronic polymorphisms (PvuII, rs2234693; XbaI, rs9340799) were examined in 184 AD patients: 157 were receiving treatment with donepezil or rivastigmine and 27 were receiving no treatment. Cognitive status was assessed using the mini mental state examination at four time points (1, 3, 9, and 15 months into therapy).
  
  
  RESULTS
  Among the patients under treatment with either ChEI, the women responded more markedly than the men. As compared with the untreated patients, the effects of treatment were statistically significant for both donepezil and rivastigmine. A significant effect of ESR1 genotypes was observed for the donepezil-treated patients, among which those carrying at least one copy of P and X alleles showed a significantly lower cognitive decline than the noncarriers.
  
  
  CONCLUSIONS
  The present data seem to confirm a sex-related influence on treatment, as the women seemed to be more sensitive to therapy and to have experienced less cognitive decline. ESR1 may be another gene contributing to interindividual variability in response to treatment with ChEIs.
authors.affiliation: CNR Institute of Molecular Biology and Pathology, c/o Department of Biology and Biotechnology, Sapienza University, Rome, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Scacchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Broggio
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corbo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D000704:Analysis of Variance; D010054:Brief Psychiatric Rating Scale; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D000068836:Rivastigmine; D012737:Sex Factors
chemical_list: D002800:Cholinesterase Inhibitors; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D000077265:Donepezil; D000068836:Rivastigmine
keywords: Alzheimer's disease; ESR1; SNP; cholinesterase inhibitors; donepezil; estrogen receptor alpha; rivastigmine; sex