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Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease
Author(s) -
Scacchi Renato,
Gambina Giuseppe,
Broggio Elisabetta,
Corbo Rosa Maria
Publication year - 2014
Publication title -
international journal of geriatric psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 129
eISSN - 1099-1166
pISSN - 0885-6230
DOI - 10.1002/gps.4043
Subject(s) - donepezil , rivastigmine , medicine , genotype , cognitive decline , dementia , cholinesterase , disease , psychology , estrogen , oncology , pharmacology , gene , biology , genetics
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 ( Pvu II, rs2234693; Xba I, 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. Copyright © 2013 John Wiley & Sons, Ltd.