Degeneration of the cholinergic system in individuals with subjective cognitive decline: A systematic review

Abstract

Background: Subjective cognitive decline (SCD) is a risk factor for future cognitive impairment and dementia. It is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. We aimed to review the current evidence about the association between SCD and biomarkers of degeneration in the cholinergic system.

Method: Original articles were extracted from three databases: Pubmed, Web of Sciences, and Scopus, in January 2023. Two researchers screened the studies independently.

Results: A total of 11 research articles were selected. SCD was mostly based on amnestic cognitive complaints. Cholinergic system biomarkers included neuroimaging markers of basal forebrain volume, functional connectivity, transcranial magnetic stimulation, or biofluid. The evidence showed associations between basal forebrain atrophy, poorer connectivity of the cholinergic system, and SCD CONCLUSIONS: Degenerative changes in the cholinergic system can be present in SCD. Subjective complaints may help when identifying individuals with brain changes that are associated with cognitive impairment. These findings may have important implications in targeting individuals that may benefit from cholinergic-target treatments at very early stages of neurodegenerative diseases.

Keywords: Basal forebrain; Basal nucleus of Meynert; Ch(4); Cholinergic system; Subjective cognitive impairment; Subjective memory complaints.