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Objectives: To determine whether intervention‐induced physical activity (PA) changes in sedentary older adults differed according to dopamine‐related genotype. Design: Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial (2010–13)). Setting: Multicenter study, 8 U.S. locations. Participants: Volunteer sample of sedentary adults aged 70 to 89 at risk of disability (N=1635). Interventions: Structured PA versus health education (HE) for an average of 2.6 years. Measurements: Single‐nucleotide polymorphisms of dopamine‐related genes (dopamine receptor (DR) D1, DRD2, DRD3, and catechol‐O‐methyltransferase (COMT)) were assessed. Average moderate to vigorous PA (MVPA) was calculated using accelerometry (min/d) at baseline and 6, 12, and 24 months. Between‐arm MVPA differences according to genotype and genotype with square root–transformed MVPA separately according to arm were tested, stratified according to race, and adjusted for multiple comparisons. Results: White participants in the PA arm (n=513) had higher average square root transformed MVPA (4.91±1.91)than those in the HE arm (n=538) (4.51±1.82) (p=.001). Between‐arm differences were greater for DRD2 Met/Met (high dopamine; HE: 4.76±1.80, PA: 5.53±1.60, p=.03) than Val/Val (low dopamine; HE: 4.58±1.92, PA: 4.81±1.83, p=.16); results were similar for COMT. In the PA arm, DRD2 Met/Met was associated with higher average MVPA (5.39±2.00) than Met/Val (4.46±2.51) (p=.01) and Val/Val (4.65±2.71) (p=.01). There were no associations for other genes. Associations were not significant in blacks but followed similar trends. Conclusion: Higher dopamine signaling may support changes in PA during an intervention. The role of dopamine‐related pathways in promoting PA participation and enhancing response to interventions in sedentary older adults should be studied. Trial Registration: clinicaltrials.gov Identifier: NCT01072500 [ABSTRACT FROM AUTHOR]

Objectives To test whether structured physical activity ( PA) is associated with a greater reduction in major mobility disability ( MMD) in older persons with metabolic syndrome (MetS) than in those without. Design Data from the Lifestyle Interventions and Independence for Elders ( LIFE) Study, a multicenter randomized trial of 1,635 persons with assessments every 6 months (average 2.7 years). Setting Eight U.S. centers. Participants Sedentary men and women aged 70 to 89 with functional limitations (N = 1,535); 100 participants were excluded because of missing MetS data. Intervention Participants were randomized to a moderate-intensity PA program (n = 766) or a health education program (n = 769). Measurements MetS was defined according to the 2009 multiagency harmonized criteria. Outcomes included incident MMD (loss of ability to walk 400 m) and persistent MMD (two consecutive MMD diagnoses or one MMD diagnosis followed by death). Results Seven hundred sixty-three (49.7%) participants met criteria for MetS. PA reduced incident MMD more than health education did in participants with MetS (hazard ratio ( HR) = 0.72, 95% confidence interval ( CI) = 0.57-0.91, P = .007) but not in those without MetS ( HR = 0.96, 95% CI = 0.73-1.25, P = .75); the test for statistical interaction was not significant ( P = .13). PA reduced the risk of persistent MMD in participants with MetS ( HR = 0.57, 95% CI = 0.41-0.79, P < .001) but not in those without MetS ( HR = 0.97, 95% CI = 0.67-1.41, P = .87). The test for statistical interaction was significant ( P = .04). Conclusion Moderate-intensity PA substantially reduces the risk of persistent MMD in older persons with functional limitations with MetS but not in those without MetS. Comparable results were observed for incident MMD. The LIFE PA program may be an effective strategy for reducing mobility disability in vulnerable older persons with MetS. [ABSTRACT FROM AUTHOR]