WWC1 Genotype Modulates Age-Related Decline in Episodic Memory Function Across the Adult Life Span

Background: Episodic memory (EM) declines with age and the rate of decline is variable across individuals. A single nucleotide polymorphism (rs17070145) in the WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and memory consolidation has previously been associated with EM performance, as well as differences in hippocampal engagement during EM tasks using functional magnetic resonance imaging (fMRI). In the current study, we explore the effect of this polymorphism on EM-related activity and cognitive performance across the adult life span using fMRI. Methods: Two hundred thirty-two healthy, Caucasian subjects (18-89 years) completed a battery of cognitive tests, as well as an EM task during an fMRI scan. Results: WWC1 T carriers had significantly better delayed recall performance than CC individuals (p=.006). The relationship between increasing age and recall scores (immediate and delayed) was also significantly different between WWC1 genotype groups (p=.01). In addition to the age-related decline in hippocampal formation (HF) activation (p<.05; false discovery rate(small volume correction-HF-region of interest)), we observed an age by WWC1 genotype interaction on HF activation during encoding and retrieval. The CC group showed a significant negative association between HF activity and increasing age, while no such association was observed in the T carrier group (left HF p=.04; r-z correlation difference during encoding and retrieval; right HF p=.0008; r-z correlation difference during retrieval). Conclusions: Our results show a dynamic relationship between rs17070145 polymorphism and increasing age on neuronal activity in the hippocampal region.