This cross-sectional multimodal neuroimaging study examined whether three MRI-derived structural atrophy subtypes of Alzheimer's disease (hippocampal-sparing [HpSp-MRI], typical [tAD-MRI], and limbic-predominant [LP-MRI]) show distinct functional profiles, using resting-state fMRI (intra- and internetwork connectivity) and EEG (spectral power and microstate dynamics) in 116 AD patients and 74 cognitively unimpaired controls.
HpSp-MRI patients showed lower intranetwork connectivity than LP-MRI and tAD-MRI groups in the visual, somatomotor, and dorsal attention networks; LP-MRI and tAD-MRI differed in ventral attention network connectivity; LP-MRI had stronger internetwork connectivity in select network pairs; and EEG revealed a possible difference in microstate 3-to-1 transition between LP-MRI and tAD-MRI subtypes.
Cross-sectional design prevents causal or longitudinal inference about subtype progression. The sample size (116 AD patients across three subtypes) limits statistical power for subgroup analyses. EEG microstate findings were described as a "possible difference," suggesting preliminary or marginal significance.
AD structural atrophy subtypes carry distinct functional brain network signatures — clinicians and researchers developing network-targeted interventions (e.g., brain stimulation) should consider subtype classification, as a one-size-fits-all approach may miss subgroup-specific targets.
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