Background/Aims: Subjective memory impairment (SMI) has been suggested as a manifestation of Alzheimer’s Disease (AD) preceding mild cognitive impairment (MCI). In this study, we determined the volumes of the hippocampus, the entorhinal cortex (EC) and the amygdala to provide biological evidence for AD in SMI. Methods: Regional volumetric measures were manually traced on 3-Tesla MRI scans. Results: Total brain volume did not differ between the groups. Individuals with SMI had reduced volumes of the hippocampus bilaterally (right p = 0.001; left p < 0.001), the bilateral EC (right p = 0.031, left p = 0.006) and the right amygdala (p = 0.01) compared to the control group. Conclusion: Volume reduction of bilateral hippocampus, bilateral EC and right amygdala supports the concept of SMI as a very early manifestation of AD prior to MCI. SMI may indicate awareness of a degenerative process that can still be functionally compensated.

The negative effect of ApoE4 on episodic memory and hippocampal volume in SMI supports SMI as a prodromal condition of AD. The positive effects of ApoE4 in subjects without SMI adds to a number of reports on positive ApoE4 effects in young and very old individuals.