Conclusion
MCI, atrophy-
DISEASE
In conclusion, we demonstrated that the response to donepezil treatment in MCI individuals differs depending on MRI subtypes. Our data suggest that donepezil should be better prescribed for MCI individuals with minimal atrophy- or hippocampal-sparing-like MRI patterns. Future studies will need to expand on these findings using long-term follow-up assessments and biomarker-based protocols. Such future studies may help to clarify whether these specific subtypes exhibit different AD biomarker trajectories and significantly delayed cognitive and functional decline under long-lasting donepezil treatment. Our data also confirmed that operationalizing biological heterogeneity as a continuous phenomenon has higher sensitivity in capturing differences in the response to donepezil over the conventional categorical subtyping approach, particularly in individuals at prodromal stages of the disease and in cohorts limited in size. This finding adds to the emerging notion that continuous subtyping is superior to categorical subtyping [