Mapping Subjective Cognitive Decline to a Common Brain Network and Linking to Gene Expression Profiles

Motivation: Whether the inconsistent findings of neuroimaging studies of subjective cognitive decline (SCD) could localize to a common brain network. Goal(s): Our goal was to determine the convergent brain substrates of SCD and the associated microbiological profiles. Approach: We used 'coordinate network mapping', utilizing a normative connectome (n = 1,000) of resting-state fMRI data to identify regions commonly connected to findings across all included studies. We decoded this convergent network through microscale transcriptomic and chemo-architectures. Results: The heterogeneous findings localized to DMN and SMN, and colocalized with brain-wide gene expression involved in cellular signaling-related biological processes, and aligned with certain neurotransmitter systems. Impact: Heterogeneous neuroimaging findings of SCD converge on common brain networks, which is linked to specific biological processes and neurotransmitters. This comprehensive understanding of the neural substrates underlying SCD may inform more targeted strategies to prevent dementia.