FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease

• Published in: Clinical interventions in aging 2014-01, Vol.9, p.1783-1791
• Main Authors: Paroni, Giulia, Seripa, Davide, Fontana, Andrea, D'Onofrio, Grazia, Gravina, Carolina, Urbano, Maria, Cascavilla, Leandro, Pellegrini, Fabio, Greco, Antonio, Pilotto, Alberto
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase inhibitors; Activities of daily living; Aged; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoproteins; Brain - drug effects; Cholinesterase Inhibitors - therapeutic use; Cognitive ability; Dementia; Drug metabolism; Drug therapy; Drugs; Enzyme inhibitors; Female; Forkhead box O1; Forkhead Box Protein O1; Forkhead Transcription Factors - genetics; Galantamine - therapeutic use; Gene Frequency - genetics; Genetic aspects; Genetic Loci - genetics; Genotype; Haplotypes - genetics; Humans; Indans - therapeutic use; Male; Metabolism; Original Research; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Pathogenesis; Patient outcomes; Patients; Phenylcarbamates - therapeutic use; Physiology; Piperidines - therapeutic use; Properties; Prospective Studies; Response to treatment; Rivastigmine; Substance abuse treatment; Systematic review; Transcription factors
• ISSN: 1178-1998; 1176-9092; 1178-1998
• DOI: 10.2147/CIA.S64758

Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer's disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD. In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion. A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510-70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups. FOXO1 may influence the clinical response to AChEIs in AD patients.