Episodic memory-associated weighted atrophy network mapping in mild cognitive impairment and subjective cognitive decline: a multi-center study

This study localizes episodic memory-associated impaired networks in mild cognitive impairment (MCI) and subjective cognitive decline (SCD) using a weighted key atrophy network mapping method, and investigates whether repetitive transcranial magnetic stimulation (rTMS) can modulate them. Replicability was assessed across three independent cohorts involving 1312 subjects. First, single-subject key atrophy maps were constructed by comparing cortical thickness with cognitively normal groups and retaining regions showing significant thickness-memory correlations. Second, these maps served as seeds for functional connectivity analysis in a large normative connectome, generating atrophy networks weighted by atrophy extent. Third, group-level comparisons identified impaired networks in MCI and SCD, and methodological reliability was further validated against a memory network derived from patients with focal brain lesions. Finally, the impaired networks were experimentally modulated via a 4-week rTMS intervention (25 MCI, 13 SCD). Despite substantial individual-level heterogeneity, atrophied regions in most MCI patients were functionally connected to a common episodic memory-associated impaired network. This phenomenon was not significant in SCD patients. Both lesion-memory network mapping and cross-dataset validation confirmed consistency across cohorts. Critically, rTMS can modulate the impaired network in MCI patients, primarily reflected by enhanced functional connectivity within this network. In conclusion, this study developed a robust weighted key atrophy network mapping method, localizing common episodic memory-associated impaired networks in MCI/SCD. Modulation of this impaired network may serve as a potential therapeutic strategy to delay MCI progression.