Age-Modulated Associations between KIBRA, Brain Volume, and Verbal Memory among Healthy Older Adults

The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The <i>KIBRA</i> single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between <i>KIBRA</i> alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, <i>n</i> = 38), young old (ages 65-72, <i>n</i> = 45), and older old (ages 73-92, <i>n</i> = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither <i>KIBRA</i> nor the interaction between <i>KIBRA</i> and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that <i>KIBRA</i> results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.