POOR SERIAL POSITION EFFECT PERFORMANCE IS CORRELATED WITH REDUCED CORTICAL AND HIPPOCAMPAL VOLUMES IN MILD COGNITIVE IMPAIRMENT

Serial position effects (SPE) refer to the tendency to better recall the beginning (primacy effect) and end (recency effect) items of a series. Abnormal SPE in word list learning have been demonstrated in Alzheimer's disease. Its association with structural brain changes in mild cognitive impairment (MCI) remains unclear. We sought to elucidate the relationship between SPE and regional grey matter volumes in subjects with MCI. 119 subjects with MCI (MMSE ≥24; CDR <1) and 68 cognitively normal (CN; CDR 0) controls were studied. All subjects underwent a comprehensive neuropsychological assessment, ApoE genotyping, and volumetric MRI brain scans. The 10-word immediate recall task from the ADAS-Cog were used to assess SPE performance, specifically by looking at recall performance for the first 3 words (primacy region) and last 3 words (recency region) of all 3 trials. MCI subjects were classified as having good SPE performance (>50% recall on both total primacy and total recency words) or poor SPE performance. MRI sequences were segmented to generate regional grey matter (GM) and white matter (WM) volumes using voxel-based morphometry, and whole hippocampal and subfield volumes using Freesurfer 6.0. 67 MCI subjects had Good SPE, and 52 had Poor SPE. All MCI subjects were older, had less education, and had worse neuropsychological scores than CN subjects. Only Poor SPE subjects had a higher prevalence of the ApoE ε4 allele.[Table 1] Poor SPE subjects showed reduced volumes in the cortical GM regions and various hippocampal subfields, compared to CN subjects. Good SPE subjects did not show similar trends. [Table 2] ApoE ε4 positive subjects with Poor SPE showed markedly reduced whole hippocampal volumes than Good SPE or CN subjects. [Figure 1] No interaction effect was found between ApoE and SPE for cortical GM volumes,[Figure 2]. Poor SPE in subjects with MCI is associated with reduced cortical and hippocampal volumes. ApoE ε4 positive MCI subjects with poor SPE show even greater hippocampal volume reductions. Poor SPE might be indicative of an underlying neurodegenerative pathology, and may be used to identify MCI subjects at high risk of AD for management and clinical trials. Association between hippocampal volumes and SPE conditions relative to controls for ApoE ε4 positive and negative subjects. Association between cortical GM volumes and SPE conditions relative to controls for ApoE ε4 positive and negative subjects.