Hippocampal connectivity may predict cholinesterase inhibitors response in mild Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer's disease (AD) is a neurodegenerative disease that has been related to impairment of cholinergic system1. Changes in the cholinergic pathways observed in AD would result in severe deterioration of memory3. The aim of this study is to evaluate whether cerebrospinal fluid (CSF) biomarkers (Aβ42, p‐Tau and t‐Tau), hippocampal volumes (HV) and Default Mode Network (DMN) functional connectivity (FC) could predict response to the available treatment.MethodWe evaluated 38 mild AD patients who was using cholinesterase inhibitors (AChEI) at therapeutic doses for, at least, 24 weeks. All subjects underwent clinical evaluation, neuropsychological assessment, MRI at 3 Tesla (Achieva Intera Philips) and CSF biomarkers before or shortly after the onset of cholinesterase inhibitors. They were reevaluated after a minimum period of 24 weeks. CSF biomarkers were evaluated INNOTEST® kits (Fujirebio). Hipoccampal Volumes we assessed by Fressurfer software. DMN functional connectivity was evaluated by UF2C software. Patients were classified according to the MMSE (Mini Mental Status Examination) score before and after the stable use of cholinesterases inhibitors. Patients who remained stable or improved in the MMSE were classified as ‘Responders”; and the others as “Non‐responders”. We performed logistic regression to assess prediction of the proposed biomarkers (CSF, HV and DMN FC).ResultLogistic regressions did not reveal any statistically significant results in relation to CSF or HV biomarkers. However, the complete model, containing predictors of DMN was significant (X 2 = 11,776, Nagelkerk R2 = 0,375, p = 0.008). Only right hippocampal connectivity predicted AChEI response (p= 0.017), showing that the higher the hippocampus FC, better the response to AChEI.ConclusionRight hippocampus FC could predict the response to AChEI in our model. However more controlled studies are needed for safer conclusion.