Brain resting-state functional connectivity (rsFC), white matter (WM) integrity, and cortical morphometry, as well as neuropsychological performance, have seldom been studied together to differentiate Alzheimer's disease (AD), mild cognitive impairment (MCI), and elderly cognitively healthy comparison (eCHC) samples in the context of the same study. We examined brain rsFC in samples of patients with mild AD (n = 50) and MCI (n = 49) in comparison with eCHC samples (n = 48) and then explored whether rsFC abnormalities can be linked to underlying gray matter (GM) volumetric and/or WM microstructural abnormalities. The mild AD sample showed significantly increased rsFC in the executive control network (ECN) and dorsal attention network (DAN) compared with the eCHC sample, and increased rsFC in ECN compared with MCI. Brain regions corresponding to both these resting-state networks (RSNs) showed significant reduction in fractional anisotropy in mild AD in comparison with eCHC. Significant GM volumetric reductions were observed in brain regions corresponding to both RSNs in the mild AD sample compared with MCI as well as eCHC samples. The association of default mode network–DAN anticorrelation with cognitive performances differentiated mild AD and MCI from eCHC sample. These findings highlight the association between brain structural and functional abnormalities as well as cognitive impairment that enables differentiation between early AD, MCI, and eCHC samples.
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