Resting state functional connectivity abnormalities and delayed recall performance in patients with amnestic mild cognitive impairment

Amnestic Mild Cognitive Impairment (aMCI) represents the transition between healthy aging and Alzheimer's dementia (AD) wherein gradual impairment of cognitive abilities, especially memory sets in. Impairment in episodic memory, especially delayed recall, is a hallmark of AD and therefore, patients with aMCI with more severe impairment in episodic memory are considered to be at greater risk of imminent conversion to AD. Brain structural and functional abnormalities were examined by comparing gray matter volumes, white matter micro-structural integrity and resting state functional connectivity (rsFC), between patients with aMCI (n = 46) having lower vs. higher episodic memory delayed recall (EM-DR) performance scores, correcting the influences of age, sex, number of years of formal education and total brain volumes using voxel-based morphometry, whole-brain tract based spatial statistics and dual regression analysis respectively. 'Low' performers (n = 27) when compared to 'high' performers (n = 19) showed significantly increased rsFC in the dorsal attention network (DAN) and central executive network (CEN) in the absence of demonstrable gray matter volumetric or white matter micro-structural integrity differences at family-wise error (FWE) corrected (p < 0.05) significance threshold. Follow-up data available for 38 (low performers = 22; high performers = 16) of the above 46 subjects (82.60% follow-up rate) over a median follow-up period of 24.5 months revealed that 7 subjects (18.42%) had converted to dementia. These converted subjects included 5 of the 22 low performers (22.72%) and 2 of the 16 high performers (12.5%) within the follow-up sample (n = 38). The results of the study indicate that imminent conversion of aMCI to dementia is higher in low performers in comparison to high performers, which may be characterized by increased rsFC in task positive networks, viz., DAN and CEN, as opposed to gray or white matter structural changes. This finding, therefore, might be considered as a prognostic indicator of progression from aMCI to dementia.