Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long-term cognitive and functional changes in
Maria V Pamio1, Caterina Trevisan1, Sabrina Pigozzo1
1Department of Medicine (DIMED), Geriatrics Division, University of Padua, Padua, Italy.
Aim:
We investigated the associations of the single-nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil.
Methods:
Sixty-five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini-Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated.
Results:
Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini-Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type.
Conclusion:
The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.
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