Functional connectivity alterations in objectively defined subtle cognitive decline: A cross-sectional functional MRI study in cognitively healthy older adults

Background: The aging of the population is leading to an increase in the incidence of neurocognitive disorders, particularly Alzheimer's disease, which has become a significant public health priority. Given the importance of early intervention in neurocognitive disorders, the identification of objectively defined subtle cognitive decline (Obj-SCD) may lead to early identification and better odds of slowing disease progression. Objective: To characterize the connectivity patterns of subjects with Obj-SCD. Methods: Fifty-one healthy adults (21 with Obj-SCD and 30 controls) over 55 years old underwent functional MRI and neuropsychological evaluations. MRI scans were conducted using a 3.0 Tesla scanner, and the data were preprocessed and denoised with CONN and SPM software, followed by independent component analysis (ICA) for identifying 20 brain networks and region-of-interest (ROI) analyses for assessing functional connectivity. The thresholds for the results were p < 0.05 for connections and FDR-corrected p < 0.05 for clusters. Results: Compared with controls, individuals with Obj-SCD exhibited both hyperconnectivity and hypoconnectivity across key brain networks; increased activity was observed in the left angular and right lingual gyri, which showed greater connectivity with the language and visual networks but reduced connectivity with the somatosensory and dorsal attention networks. The default mode and central executive networks also showed functional connectivity alterations, whereas the salience network exhibited hypoconnectivity. Conclusions: The connectivity alterations of individuals with Obj-SCD may reflect compensatory mechanisms, early network disruptions, or both. fMRI-based analyses could aid in detecting these early changes, providing opportunities for interventions that may slow or prevent further cognitive decline.