The Effect of Cholinesterase Inhibitors on Neurodegeneration in Individuals with Amnestic Mild Cognitive Impairment.

Objective: Cholinesterase inhibitors (ChEIs) are effective in treating mild to moderate Alzheimer's disease (AD) dementia by compensating for acetylcholine deficiency. While their use in mild cognitive impairment (MCI) lacks strong trial support, some studies suggest they may delay neurodegeneration. This study aims to investigate ChEIs' neuroprotective effects in individuals with amnestic MCI (aMCI) using multi-modal neuroimaging, and to determine if amyloid-beta (Aβ) deposition influences these effects.

Methods: Longitudinal data from a cohort study were retrospectively analyzed. A total of 118 aMCI patients (ages 55- 90), who underwent baseline evaluations encompassing the assessment of ChEI use and [¹¹C] Pittsburgh compound B-positron emission tomography (PET), were included in the analyses. All participants also received baseline and 2-year follow-up magnetic resonance imaging and [¹⁸F] fluorodeoxyglucose-PET imaging.

Results: The ChEI use group exhibited a significantly lesser decline in AD-signature region cerebral metabolism (AD-CM) over a 2-year period than the ChEI non-use group (B = 0.089, 95% CI: 0.030-0.149). However, there was no significant difference in the 2-year change of AD-signature region cortical thickness (AD-CT) (B = 0.032, 95% CI: -0.075 to 0.138) and hippocampal volume (B = -88.013, 95% CI: -323.900 to 147.874) between the ChEI use and non-use groups. The presence of Aβ pathology did not moderate the effect of ChEI use on AD-CM, AD-CT, or hippocampal volume.

Conclusion: The findings suggest that ChEIs may delay functional neurodegeneration in aMCI individuals, irrespective of the presence of amyloid pathology.