Background: The response to cholinesterase inhibitors (ChEIs) treatment is variable in patients with Alzheimer's disease (AD). Patients and physicians would benefit if these drugs could be targeted at those most likely to respond in a clinical setting. Therefore, this study aimed to evaluate the ability of cerebrospinal fluid (CSF) AD biomarkers, hippocampal volumes, and Default Mode Network functional connectivity to predict clinical response to ChEIs treatment in mild AD. Methods: We followed up on 39 mild AD patients using ChEIs at therapeutic doses. All subjects underwent clinical evaluation, neuropsychological assessment, magnetic resonance imaging examination, and CSF biomarkers quantification at the first assessment. The Mini-Mental Status Examination (MMSE) was used to measure the global cognitive status before and after the follow-up. "Responders" were considered as those who have remained stable or improved the MMSE score between evaluations and "Nonresponders" as those who have worsened the MMSE score. We performed univariate and multivariate logistic regressions to predict the clinical response from each biomarker. Results: About 35.89% of patients were classified as "Responders" to ChEIs treatment after the follow-up. The multivariate model with measures of Right Hippocampus (RHIPPO), adjusted for gender and interval between assessments, was significant (odds ratio: 1.09 [95% confidence interval, 1.00-1.19], p = 0.0392). This model achieved an accuracy of 77.60%. Conclusion: Our findings suggest that the functional connectivity of RHIPPO might be an early imaging biomarker to predict clinical response to ChEIs drugs in mild AD. Impact statement The functional connectivity of the right hippocampus showed a direct relationship with the clinical response to cholinesterase inhibitors (ChEIs) treatment in patients with mild Alzheimer's disease. Transposing our findings to clinical settings could allow physicians to prescribe ChEIs for patients for whom treatment would be most beneficial.
Keywords: Alzheimer's disease; cholinesterase inhibitors; functional connectivity; hippocampus.