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Magnified effects of the COMT gene on white-matter microstructure in very old age

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Abstract

Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60–87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81–87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60–66 and 72–78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

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Acknowledgments

We thank the SNAC-K nurses, medical doctors, and psychologists for their contribution to data collection. This research has made use of the SMILE medical imaging laboratory at Karolinska University Hospital, Stockholm, Sweden. This research was supported by the Swedish Ministry for Social Affairs as well as by grants from the Swedish Council for Working Life and Social Research (E.L., L.F., L.B.), the Swedish Research Council (L.F., L.B.), Swedish Brain Power (L.F., L.B., L.K.), Emil och Wera Cornells Stiftelse (L.K.), an Alexander von Humboldt Research Award (L.B.), and a donation from the af Jochnick Foundation (L.B.).

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Correspondence to Goran Papenberg.

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Papenberg, G., Lövdén, M., Laukka, E.J. et al. Magnified effects of the COMT gene on white-matter microstructure in very old age. Brain Struct Funct 220, 2927–2938 (2015). https://doi.org/10.1007/s00429-014-0835-4

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