Purpose: To determine whether individuals with subjective cognitive decline (SCD) exhibit functional and structural brain alterations by using resting-state functional and structural magnetic resonance (MR) imaging. Materials and Methods: This study received institutional review board approval, and all participants gave informed consent. Resting-state functional MR imaging and structural MR imaging techniques were used to measure amplitude of low-frequency fluctuations (ALFF) and regional gray matter volume in 25 subjects with SCD (mean age, 65.52 years +/- 6.12) and 61 control subjects (mean age, 64.11 years +/- 8.59). Voxel-wise general linear model analyses were used to examine between-group differences in ALFF or in gray matter volume and to further determine the brain-behavioral relationship. Results: Subjects with SCD exhibited higher ALFF values than did control subjects in the bilateral inferior parietal lobule (left: 0.44 +/- 0.25 vs 0.27 +/- 0.18, respectively; P = .0003; right: 1.46 +/- 0.45 vs 1.10 +/- 0.37, respectively; P = .0015), right inferior (0.45 +/- 0.15 vs 0.37 +/- 0.08, repectively; P = .0106) and middle (1.03 +/- 0.32 vs 0.83 +/- 0.20, respectively; P = .0008) occipital gyrus, right superior temporal gyrus (0.11 +/- 0.07 vs 0.07 +/- 0.04, respectively; P = .0016), and right cerebellum posterior lobe (0.51 +/- 0.27 vs 0.39 +/- 0.15, respectively; P = .0010). In the SCD group, significant correlations were found between Auditory Verbal Learning Test recognition scores and ALFF in the left inferior parietal lobe (r = -0.79, P < .001) and between Auditory Verbal Learning Test immediate recall scores and ALFF values in the right middle occipital gyrus (r = -0.64, P = .002). Nonsignificant group differences were found in gray matter volume (P > .05, corrected). Conclusion: Individuals with SCD had altered spontaneous functional activity, suggesting that resting-state functional MR imaging may be a noninvasive method for characterizing SCD. (C) RSNA, 2016