Poster C41, Sunday, March 26, 5:00 – 7:00 pm, Pacific Concourse
Additive effects of two DRD2 polymorphisms on working memory performance, and striatal functional and structural MRI measurements
Xin Li1, Micael Andersson2, Lars Nyberg2, Jonas Persson1; 1Aging Research Center (ARC), Karolinska Institute and Stockholm University, 2Umeå Center for Functional Brain Imaging (UFBI), Umeå University
The neurotransmitter dopamine (DA) is critical for high-level cognition, including working memory (WM). The D2 subtype of DA receptors has the highest densities in striatum, including caudate and putamen. The T allele of the C957T polymorphism of the D2 receptor gene (DRD2) has been associated with reduced extrastriatal D2 receptor availability and lower striatal DA levels, and the A1 allele of the DRD2/ANKK1-TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. Here we examined the combined effects of these two DRD2 polymorphisms on WM manipulation, brain volume and brain activation in younger (n=191) and older (n=111) adults. We further investigated whether these effects were magnified in old age. Participants were scanned while performing a WM task in which the information to be kept in memory was maintained (low fronto-striatal demand) or manipulated (high fronto-striatal demand). Results showed that individuals who carry two beneficial alleles, compared to carriers of 1 or 0 beneficial alleles, were reliably better in the manipulation WM condition, had larger right caudate volume, and exhibited less BOLD activation in the left caudate nucleus, suggesting more efficient caudate function. Moreover, the genetic effects on striatal volume and activity were only seen in older adults, suggesting magnification of genetic effects on brain volume and functional brain activity in aging. These results demonstrate an addictive effect of two DRD2 polymorphisms on striatal structure and function, and that this effect is related to manipulation of information in WM, and provides new evidence for magnified genetic effects in aging.
Topic Area: EXECUTIVE PROCESSES: Working memory