INCREASED FUNCTIONAL CONNECTIVITY OF DEFAULT MODE NETWORK IN PATIENTS WITH MODERATE AMNESTIC MILD COGNITIVE IMPAIRMENT: INFLECTION POINT IN COURSE OF DISEASE

Abstract

The neuroimaging biomarkers model of the progression from MCI to AD indicated there is first increased brain functional activation at early MCI, followed by reduced activation at the late stage. Such a functional inflection point of “increase followed by decrease” could serve as a marker of the onset of abnormal cognitive behavior. The alteration of functional connectivity (FC) of default mode network (DMN) has been reported in patients with amnestic mild cognitive impairment (aMCI). However, due to the lack of a finer MCI stage, no studies exist that examined stage-dependent DMN-FC changes throughout the course of aMCI. Utilizing the extreme groups approach on the performance of episodic memory tasks, 45 aMCI subjects were divided into mild (10, age = 61.60 ± 7.53), moderate (19, age = 64.94 ± 6.30) and severe (16, age = 66.06 ± 8.49) stages. All subjects underwent an extensive neuropsychological assessment. Both T1-weighted structure images and resting-state functional images were acquired. Independent component analysis was used to assess DMN for individual patients in each of the three stages. Partial correlation analysis was performed to examine the relationship between the ROI-based FC in DMN and the neuropsychological performances with gender, age and years of education as covariates. Instead of finding that continued monotonic decline as the case for the hippocampus volume (p = 0.030, p = 0.029, p = 0.024 for left, right and total hippocampus volumes respectively in a trend analysis), we observed an increase in DMN functional connectivity from mild aMCI to moderate aMCI and a decrease to severe aMCI [p (FDR-corrected for multiple comparisons) < 0.05], mainly in the left precuneus and superior parietal lobe. Moreover, the FC of the left precuneus is significantly correlated with backward (r = -0.338, p = 0.029) and digit span (r = -0.328, p = 0.034).