title: Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment.
abstract: Amnestic mild cognitive impairment (aMCI) is believed to represent a transitional stage between normal healthy ageing and the development of dementia. In particular, aMCI patients have been shown to have higher annual transition rates to Alzheimer's Disease (AD) than individuals without cognitive impairment. Despite intensifying interest investigating the neuroanatomical basis of this transition, there remain a number of questions regarding the pathophysiological process underlying aMCI itself. A number of recent studies in aMCI have shown specific impairments in connectivity within the default mode network (DMN), which is a group of regions strongly related to episodic memory capacities. However to date, no study has investigated the integrity of the DMN between patients with aMCI and those with a non-amnestic pattern of MCI (naMCI), who have cognitive impairment, but intact memory storage systems. In this study, we contrasted the DMN connectivity in 24 aMCI and 33 naMCI patients using seed-based resting state fMRI. The two groups showed no statistical difference in their DMN intra-connectivity. However when connectivity was analysed according to performance on measures of episodic memory retrieval, the two groups were separable, with aMCI patients demonstrating impaired functional connectivity between the hippocampal formation and the posterior cingulate cortex. We provide evidence that this lack of connectivity is driven by impaired communication from the posterior cingulate hub and does not simply represent hippocampal atrophy, suggesting that posterior cingulate degeneration is the driving force behind impaired DMN connectivity in aMCI.
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Dunn
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Shantel L
authors.initials: SL
authors.lastname: Duffy
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Simon J G
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Naismith
authors.affiliation: Healthy Brain Ageing Program, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: Shine
mesh_terms: D000368:Aged; D000647:Amnesia / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D063132:Connectome / Q000379:methods; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D061212:Memory, Episodic; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology
keywords: Amnestic; Default mode network; Functional magnetic resonance imaging; Memory; Mild cognitive impairment; Resting state functional connectivity