Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory).

Spatial navigation relies on multiple mnemonic mechanisms and previous work in younger adults has described two separate types of spatial memory. One type uses directional as well as boundary-related information for spatial memory and mainly implicates the hippocampal formation. The other type has been linked to directional and landmark-related information and primarily involves the striatum. Using a virtual reality navigation paradigm, we studied the impacts of aging and a single nucleotide polymorphism (SNP rs17070145) of the KIBRA gene (official name: WWC1) on these memory forms. Our data showed that older adult's spatial learning was preferentially related to processing of landmark information, whereas processing of boundary information played a more prominent role in younger adults. Moreover, among older adults T-allele carriers of the examined KIBRA polymorphism showed better spatial learning compared to C homozygotes. Together these findings provide the first evidence for an effect of the KIBRA rs17070145 polymorphism on spatial memory in humans and age differences in the reliance on landmark and boundary-related spatial information.

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