BRAIN MORPHOMETRICAL CORRELATES UNDERLYING COGNITIVE PERFORMANCE IN A GENETICALLY ENRICHED SAMPLE OF HEALTHY INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

Abstract

Progressive decline in episodic memory is a distinct feature of Alzheimer's disease (AD). In AD patients, APOE status moderates the rate of cognitive detriment with APOE-ε4 carriers showing significantly more rapid memory decay as well as lower scores in cognitive tests compared to non-carriers. However, the impact of the APOE genotype on cognitive performance and brain morphometry in healthy middle-aged people remains unclear. We included 521 middle-aged healthy individuals and grouped them according to their APOE genotype (253 non-carriers, 204 heterozygotes and 64 homozygotes for the ε4 risk allele). All subjects underwent cognitive evaluation using the Memory Binding Test (MBT) as well as high-resolution structural magnetic resonance imaging (sMRI). We adopted a multiple regression approach using voxel-based morphometry to determine relationships between regional grey matter volumes and MBT performance and whether this relationship is modulated by APOE status. We found no significant differences among genotype groups in any of the evaluated MBT subscales. Compared to non-carriers, APOE-ε4 carriers displayed significantly greater positive correlations between regional GM volumes and cognitive performance, in four MBT subscales. The involved brain areas included the bilateral insula, inferior temporal lobes, cingulate cortex and hippocampus. In asymptomatic people, APOE-ε4 moderates the association between regional GM volume and cognitive performance in episodic memory. These data shed light on the impact of such risk allele on cognitive resources in the healthy population and further improve our knowledge on the mechanisms relating APOE, cognitive decline and patterns of brain atrophy.