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.
