Subjective memory complaints are associated with altered resting-state functional connectivity but not structural atrophy.

Research indicates that a subtle cognitive decline, accompanied by pathological changes, occurs in individuals with subjective memory complaints (SMC). However, there is less evidence regarding the measurement of resting-state functional connectivity to detect subtle brain network alterations in neurodegenerative illnesses before cognitive change manifestation. We investigated the correlation between SMC and cognitive performance and explored functional and structural brain changes underlying SMC severity, using behavioral and brain imaging data-driven approaches. We observed that SMC was associated with depression but not with cognitive test scores, implying that SMC represent the “worried-well”; however, this model explains only 15% of the target variance. Using a conservative threshold, we observed connectivity related to SMC severity in the lingual gyrus, cuneus, anterior insula, and superior parietal lobule. Post-hoc analysis indicated that occipital and parietal functional connectivity increased with SMC severity. In contrast, volumetric alterations were not associated with SMC, even after applying a liberal threshold. Our findings suggest that altered resting-state functional connectivity in regions associated with SMC might reflect early compensatory changes that occur before cognitive and structural abnormalities develop.