Mild Cognitive Impairment and Astrocytic Influences Affecting Network Communication

Abstract

Amnestic mild cognitive impairment (MCI) is generally understood to mean an age-related impairment in cognition beyond that normally observed in the elderly, where amnestic refers to a loss of the ability to recall stored information. The significance of this classification has traditionally rested on a presumptive clinical indication of dementia, based on a documented 5% to 10% annual rate of progression to dementia, a rate much higher than the 1% to 2% incidence observed within the general population. Because recollection mechanisms have been shown to center on the hippocampal cortical network (HCN), amnestic MCI is likely to entail an interruption of this network. Accumulating evidence indicates that a crucial cellular element regulating information flow in the HCN is the astrocyte. By extension, astrocytic mechanisms involved in regulating information flow within the HCN are likely to be disrupted in MCI. Consistent with this, astrocyte influence in memory networks is multimodally affected in MCI and AD patients, with impairments seen, for example, in interregional oscillatory coupling. Astrocyte pathologies thus appear to drive clinically relevant phenotypes of MCI and could represent novel and significant therapeutic targets for MCI treatment. Understanding the mechanisms astrocytes employ to enable communication within the HCN may not only advance our understanding of how and which processes are likely to go awry in MCI, but how they may be treated to arrest the loss of this most iconic MCI symptom.