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.
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 ADpatients: 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: Juyoun Lee; Hanna Cho; Seun Jeon; Hee Jin Kim; Yeo Jin Kim; Jeongmin Lee; Sung Tae Kim; Jong-Min Lee; Juhee Chin; Samuel N Lockhart; Ae Young Lee; Duk L Na; Sang Won Seo Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Harald Hampel; Nicola Toschi; Claudio Babiloni; Filippo Baldacci; Keith L Black; Arun L W Bokde; René S Bun; Francesco Cacciola; Enrica Cavedo; Patrizia A Chiesa; Olivier Colliot; Cristina-Maria Coman; Bruno Dubois; Andrea Duggento; Stanley Durrleman; Maria-Teresa Ferretti; Nathalie George; Remy Genthon; Marie-Odile Habert; Karl Herholz; Yosef Koronyo; Maya Koronyo-Hamaoui; Foudil Lamari; Todd Langevin; Stéphane Lehéricy; Jean Lorenceau; Christian Neri; Robert Nisticò; Francis Nyasse-Messene; Craig Ritchie; Simone Rossi; Emiliano Santarnecchi; Olaf Sporns; Steven R Verdooner; Andrea Vergallo; Nicolas Villain; Erfan Younesi; Francesco Garaci; Simone Lista Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Anna Morozova; Yana Zorkina; Olga Abramova; Olga Pavlova; Konstantin Pavlov; Kristina Soloveva; Maria Volkova; Polina Alekseeva; Alisa Andryshchenko; Georgiy Kostyuk; Olga Gurina; Vladimir Chekhonin Journal: Int J Mol Sci Date: 2022-01-22 Impact factor: 5.923
Authors: Katherine A Lin; Kingshuk Roy Choudhury; Bharath G Rathakrishnan; David M Marks; Jeffrey R Petrella; P Murali Doraiswamy Journal: Alzheimers Dement (N Y) Date: 2015-09-01