Alzheimer Disease: Evaluation of a Functional MR Imaging Index as a Marker

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Abstract
To measure changes in functional synchrony in the hippocampus in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Three subject groups (nine cognitively healthy elderly control subjects, 10 patients with probable AD, and five subjects with MCI) underwent resting-state functional magnetic resonance (MR) imaging for measurement of functional synchrony in the hippocampus. Functional synchrony was defined and quantified as the mean of the cross-correlation coefficients of spontaneous low frequency (COSLOF) components between possible pairs of voxel time courses in a brain region, or the COSLOF index. The two-tailed Student t test was used to determine differences in the COSLOF index between the control group, the probable AD group, and the MCI group. An operating characteristic curve was calculated to graphically depict the tradeoff between sensitivity and specificity of the COSLOF index. Functional synchrony quantified with the COSLOF index was obtained in AD, MCI, and control subjects. COSLOF index values were significantly lower in AD patients than in control subjects (t = 4.32, P <.0012). For MCI subjects, COSLOF index values were significantly higher than those of AD patients (t = -2.4052, P <.047) but significantly lower than those of control subjects (t = 2.257, P <.043). The exponential-class curve significantly fits the relationship between the COSLOF index and the Mini-Mental Status Examination score (chi(2) = 20.4), indicating the rapid decrease in cognitive capacity below a threshold of the COSLOF index. Our results suggest that the COSLOF index could be used as a noninvasive quantitative marker for the preclinical stage of AD.