Associative memory deficits in mild cognitive impairment: The role of hippocampal formation

Neuropathological events featuring early stages of Alzheimer's disease (AD) appear in the entorhinal cortex (EC), subiculum (SB) and cornu ammonis 1 (CA1) of hippocampus, which may account for associative memory deficits in non-demented people with mild cognitive impairment (MCI). To test this hypothesis in vivo, we investigated whether volume changes in these regions are related to failures in associative memory in MCI as compared to cognitively normal (CN) elderly subjects. Volume changes in EC and hippocampal subfields were determined by using deformation-based morphometry techniques applied to probabilistic cytoarchitectonic maps derived from post mortem human brains. CN subjects were distinguished from MCI patients by firstly identifying local volume differences in EC and hippocampus, and then evaluating the way in which these anatomical changes correlated with performance in a non-intentional face-location association task. MCI patients not only performed worse than CN elders in building new associations, but they were further unable to benefit from semantic encoding to improve episodic binding. According to our initial hypothesis, local volume reductions in both EC and hippocampal CA accounted for group differences in associative memory whereas atrophy in CA, but not in EC, accounted for semantic encoding of associations. Two main conclusions can be drawn from the present study: i) access to semantic information during encoding does not reduce the episodic deficit in MCI; and ii) EC and hippocampal CA, two regions early affected by AD neuropathology, are responsible, at least partially, for associative memory deficits observed in MCI patients.

► The neuroanatomical correlates of associative deficits in MCI are unexplored. ► We studied if integrity of hippocampal formation relates to associative failures. ► Volume of EC and hippocampal CA was reduced in MCI relative to controls. ► Integrity of EC and CA accounts for different aspects of associative memory in MCI.