SUMMARY Importance In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activity prevents or delays mobility disability. Objective To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability. Design, Setting, and Participants The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban and rural communities at 8 field centers throughout the US. We randomized a volunteer sample of 1,635 sedentary men and women aged 70–89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m. Interventions Participants were randomized to a structured moderate intensity physical activity program (n=818) done in a center and at home that included including aerobic, resistance and flexibility training activities or to a health education program (n=817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises. Main Outcomes and Measures The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m. Results Incident major mobility disability occurred in 30.1% (n=246/818) of physical activity and 35.5% (n=290/817) of health education participants (HR=0.82, 95%CI=0.69–0.98, p=0.03). Persistent mobility disability was experienced by 120/818 (14.7%) physical activity and 162/817 (19.8%) health education participants (HR=0.72; 95%CI=0.57–0.91; p=0.006). Serious adverse events were reported by 404/818 (49.4%) of the physical activity and 373/817 (45.7%) of the health education participants (Risk Ratio=1.08; 95%CI=0.98–1.20). Conclusions and Relevance A structured moderate intensity physical activity program, compared with a health education program, reduced major mobility disability over 2.6 years among older adults at risk of disability. These findings suggest mobility benefit from such a program in vulnerable older adults. Registration ClinicalsTrials.gov identifier NCT01072500.

BACKGROUND Weight loss is recommended for overweight and obese individuals with type 2 diabetes based on short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether intensive lifestyle intervention for weight loss decreased cardiovascular morbidity and mortality in overweight or obese adults with type 2 diabetes. METHODS We randomly assigned 5,145 overweight or obese individuals with type 2 diabetes recruited at 16 US centers to intensive lifestyle intervention (the intervention group), which promoted weight loss through decreased calorie intake and increased physical activity, or diabetes support and education (the control group). The primary outcome was the first post-randomization occurrence of a composite cardiovascular outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalized angina) over a planned maximum follow-up of 13.5 years. RESULTS The trial was stopped early based on a futility analysis when median follow-up was 9.6 years. Weight loss was greater in the intervention group than the control group throughout (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). Intensive lifestyle intervention also produced greater reductions in hemoglobin A1c and greater initial improvements in fitness and all cardiovascular risk factors, except LDL cholesterol. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83/100 person-years and 1.92/100 person-years, respectively; hazard ratio 0.95; 95% CI 0.83 to 1.09, p=0.505). CONCLUSION In our study, intensive lifestyle intervention focused on weight loss did not reduce cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.)

Aging has been targeted by genetic and dietary manipulation and by drugs in order to increase lifespan and health span in numerous models. Metformin, which has demonstrated protective effects against several age-related diseases in humans, will be tested in the TAME (Targeting Aging with Metformin) trial, as the initial step in the development of increasingly effective next-generation drugs.

Objective-The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes one-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events.Research Design and Methods-A multi-centered randomized controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with body mass index ≥25 kg/m 2 (≥27 kg/m 2 if taking insulin). An Intensive Lifestyle Intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared to a Diabetes Support and Education (DSE) condition.Results-Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (p<0.001). Mean fitness increased in ILI by 20.9% versus 5.8% in DSE (p<0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean HbA 1 c dropped from 7.3% to 6.6% in ILI (p<0.001) versus from 7.3% to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL-cholesterol, and urine albumin/creatinine improved significantly more in ILI than DSE participants (all p<0.01).Conclusions-At 1 year, ILI resulted in clinically significant weight loss in persons with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.

GE-ASSOCIATED MEMORY impairment affects an estimated one fifth to one third of older individuals and has important individual, family, and societal costs. 1,2 In older postmenopausal women, the potential impact of declining levels of sex hormones on cognitive functioning has received particular attention because of estrogen's presumptive beneficial effects on neurotransmitters, 3 neuroconnectivity, 4,5 and neuroprotection. 6 Observational studies have suggested that long-term hormone therapy may attenuate cognitive aging in postmenopausal women, although ran-domized clinical trial results are inconsistent. 7-12 The Women's Health Initiative (WHI) includes 2 randomized trials of post-menopausal hormone therapy: the estrogen-alone trial of conjugated equine estrogen (CEE) therapy in women with a prior hysterectomy and the estrogen Author Affiliations and Financial Disclosures are listed at the end of this article.