Significant effects of cholinesterase inhibitors on tau pathology in the Alzheimer's disease continuum: An in vivo positron emission tomography study.

Objectives No prior study has assessed the effects of cholinesterase inhibitors (ChEIs) on tau pathology in the brains of patients with Alzheimer's disease (AD). Using positron emission tomography, this study aimed to investigate whether ChEIs reduce tau aggregation in amyloid-positive participants. Methods We analyzed datasets from the Alzheimer's Disease Neuroimaging Initiative and included amyloid-positive participants who had undergone baseline and one- or two-year follow-up AV-1451 positron emission tomography scans. We included participants treated with and without ChEIs (ChEIs group: n=15, No-ChEIs group, n=45). The annual change in tau aggregation was calculated as the difference in AV-1451- standardized uptake value ratio (SUVR) between the two scans divided by the time between scans. Group differences in annual AV-1451-SUVR change were examined. Results We found a significantly lower annual change in AV-1451-SUVR in the Braak 1/2 regions (entorhinal cortex and hippocampus) of participants taking ChEIs. Increased AV-1451-SUVR between the 1st and 2nd examinations were observed in 22 of 45 participants not taking ChEIs and 2 of 15 participants taking ChEIs. Fisher's exact test showed a significant difference in the ratio of participants with increased AV-1451-SUVR between the groups. Conclusions The findings of this positron emission tomography study suggest that the administration of ChEIs has some neuroprotective effects in patients of the AD continuum, at least in the early stage of the disease progression. This in vivo effect may be mediated via tau, preventing amyloid β-induced neurotoxicity. This article is protected by copyright. All rights reserved.