Functional heterogeneity across structural MRI-based atrophy subtypes in Alzheimer's disease.

OBJECTIVES: This study explored whether distinct Alzheimer's disease (AD) structural atrophy subtypes exhibit divergent functional profiles. DESIGN: A cross-sectional multimodal neuroimaging and electrophysiological study. SETTING: Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China. PARTICIPANTS: A total of 116 patients with AD and 74 cognitively unimpaired controls underwent structural MRI. Patients with AD were stratified into three MRI-derived atrophy-pattern groups corresponding to hippocampal-sparing (HpSp-MRI), typical (tAD-MRI), and limbic-predominant (LP-MRI) subtypes. MEASUREMENTS: Resting-state functional MRI was used to assess intra- and internetwork functional connectivity, and EEG was used to evaluate spectral power and microstate dynamics. RESULTS: The HpSp-MRI subtype showed lower intranetwork connectivity than both the LP-MRI and tAD-MRI subtypes in the visual, somatomotor, and dorsal attention networks. The LP-MRI and tAD-MRI subtypes differed in ventral attention network connectivity. Moreover, the LP-MRI subtype exhibited stronger internetwork connectivity in specific network pairs compared with the other subtypes. EEG analysis suggested a possible difference in the microstate 3-to-1 transition between the LP-MRI and tAD-MRI groups. CONCLUSIONS: MRI-derived atrophy-pattern subtypes showed different resting-state functional connectivity profiles, providing a potential basis for personalized brain network-targeted interventions in AD.