Shannon Mance1, Andrea Rosso1, Joshua Bis2, Stephanie Studenski3, Nico Bohnen4, Caterina Rosano1. 1. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA. 2. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. 3. Geriatric Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 4. Departments of Radiology & Neurology, University of Michigan School of Medicine & Ann Arbor VA, Ann Arbor, Michigan, USA.
Abstract
OBJECTIVE: To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race. DESIGN: Cross-sectional population-based study (Cardiovascular Health Study). SETTING: Multicenter study, four U.S. sites. PARTICIPANTS: Volunteer community-dwelling adults aged 65 years and older, without evidence of Parkinson's disease (N = 3,744; 71 years; 82% White; 39% male). MEASUREMENTS: Gait speed (usual pace; m/s), physical frailty (Fried definition), and genetic polymorphism of catechol-O-methyltransferase (COMT; rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated, stratified by clinical cutoffs of gait speed (0.6 and 1.0 m/s) instead of frailty status. RESULTS: The interaction of COMT by frailty and COMT by race were P = .02 and P = .01, respectively. Compared with Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/s; P = .2). Gait speed differences were significant for frail (n = 220; 0.55 vs 0.63 m/s; P = .03), but not for prefrail (n = 1,691; 0.81 vs 0.81 m/s; P = .9) or nonfrail (n = 1,833; 0.98 vs 0.97 m/s; P = .7); results were similar in fully adjusted models. Among frail, associations were similar for Whites and Blacks, with statistical significance for Whites only. Associations stratified by clinical cutoffs of gait speed were not significant. CONCLUSION: The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared with those without frailty. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.
OBJECTIVE: To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race. DESIGN: Cross-sectional population-based study (Cardiovascular Health Study). SETTING: Multicenter study, four U.S. sites. PARTICIPANTS: Volunteer community-dwelling adults aged 65 years and older, without evidence of Parkinson's disease (N = 3,744; 71 years; 82% White; 39% male). MEASUREMENTS: Gait speed (usual pace; m/s), physical frailty (Fried definition), and genetic polymorphism of catechol-O-methyltransferase (COMT; rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated, stratified by clinical cutoffs of gait speed (0.6 and 1.0 m/s) instead of frailty status. RESULTS: The interaction of COMT by frailty and COMT by race were P = .02 and P = .01, respectively. Compared with Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/s; P = .2). Gait speed differences were significant for frail (n = 220; 0.55 vs 0.63 m/s; P = .03), but not for prefrail (n = 1,691; 0.81 vs 0.81 m/s; P = .9) or nonfrail (n = 1,833; 0.98 vs 0.97 m/s; P = .7); results were similar in fully adjusted models. Among frail, associations were similar for Whites and Blacks, with statistical significance for Whites only. Associations stratified by clinical cutoffs of gait speed were not significant. CONCLUSION: The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared with those without frailty. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.
Authors: L P Fried; N O Borhani; P Enright; C D Furberg; J M Gardin; R A Kronmal; L H Kuller; T A Manolio; M B Mittelmark; A Newman Journal: Ann Epidemiol Date: 1991-02 Impact factor: 3.797
Authors: Aron S Buchman; Joshua M Shulman; Sukriti Nag; Sue E Leurgans; Steven E Arnold; Martha C Morris; Julie A Schneider; David A Bennett Journal: Ann Neurol Date: 2012-02 Impact factor: 10.422
Authors: Laura Jean Podewils; Eliseo Guallar; Lewis H Kuller; Linda P Fried; Oscar L Lopez; Michelle Carlson; Constantine G Lyketsos Journal: Am J Epidemiol Date: 2005-04-01 Impact factor: 4.897
Authors: Calvin Hirsch; Melissa L Anderson; Anne Newman; Willem Kop; Sharon Jackson; John Gottdiener; Russell Tracy; Linda P Fried Journal: Ann Epidemiol Date: 2006-01-04 Impact factor: 3.797
Authors: Andrea L Rosso; Stephanie A Studenski; Wen G Chen; Howard J Aizenstein; Neil B Alexander; David A Bennett; Sandra E Black; Richard Camicioli; Michelle C Carlson; Luigi Ferrucci; Jack M Guralnik; Jeffrey M Hausdorff; Jeff Kaye; Lenore J Launer; Lewis A Lipsitz; Joe Verghese; Caterina Rosano Journal: J Gerontol A Biol Sci Med Sci Date: 2013-07-10 Impact factor: 6.053