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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.

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The patients and their families, the staff members of Geriatric Clinic and Services as well as the technical personnel at the Department of Neuroimaging and Interventional Neurology (N.I.I.R), NIMHANS are acknowledged for their kind involvement in the study.


This study was funded by the Department of Science and Technology (DST), Government of India (Grant No. DST-SR/CSI/70/2011 (G) dated 20.03.2012 to Dr. Srikala.Bharath).

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Correspondence to John P. John.

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Himanshu Joshi, Srikala Bharath, John P John, Shilpa Sadanand, Jitender Saini, Keshav Kumar and Mathew Varghese declare that they have no conflict of interest.

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All the procedures involving human subjects have been performed by approval with NIMHANS Institutional Ethics Review Board and in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Joshi, H., Bharath, S., John, J.P. et al. Resting state functional connectivity abnormalities and delayed recall performance in patients with amnestic mild cognitive impairment. Brain Imaging and Behavior 14, 267–277 (2020).

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  • Amnestic mild cognitive impairment (aMCI)
  • Episodic memory
  • Dementia
  • Dorsal attention network
  • Central executive network
  • Task positive network