Pulse Pressure magnifies the effect of COMT Val158Met on 15 Year Episodic Memory Trajectories

We investigated whether a physiological marker of cardiovascular health, pulse pressure (PP), and age magnified the effect of the functional COMT Val158Met (rs4680) polymorphism on 15-years cognitive trajectories [episodic memory (EM), visuospatial ability, and semantic memory] using data from 1585 non-demented adults from the Betula study. A multiple-group latent growth curve model was specified to gauge individual differences in change, and average trends therein. The allelic variants showed negligible differences across the cognitive markers in average trends. The older portion of the sample selectively age-magnified the effects of Val158Met on EM changes, resulting in greater decline in Val compared to homozygote Met carriers. This effect was attenuated by statistical control for PP. Further, PP moderated the effects of COMT on 15-years EM trajectories, resulting in greater decline in Val carriers, even after accounting for the confounding effects of sex, education, cardiovascular diseases (diabetes, stroke, and hypertension), and chronological age, controlled for practice gains. The effect was still present after excluding individuals with a history of cardiovascular diseases. The effects of cognitive change were not moderated by any other covariates. This report underscores the importance of addressing synergistic effects in normal cognitive aging, as the addition thereof may place healthy individuals at greater risk for memory decline.

<p>The Betula Study was supported by the Bank of Sweden Tercentenary Foundation, Tercentenary Foundation (Grant 1988-0082:17), the Swedish Council for Planning and Coordination of Research (Grants D1988-0092, D1989-0115, D1990-0074, D1991-0258, D1992-0143, D1997-0756, D1997-1841, D1999-0739, and B1999-474), the Swedish Council for Research in the Humanities and Social Sciences (Grant F377/1988-2000), the Swedish Council for Social Research (1998–1990: Grants 88-0082 and 311/1991-2000), the Wallenberg-scholar grant 2009 to Lars Nyberg; the Royal Swedish Society of Sciences, and Solstickan Foundation (Rolf Zetterström award) (Grants FOA11H-349 - FOA13H-090) to Ninni Persson.</p>