Multidomain lifestyle intervention for the prevention of cognitive decline in at-risk older adults in Latin America (LatAm-FINGERS): a single-blind, multicentre, randomised controlled trial.

Abstract (English)

BACKGROUND: Latin America faces a high dementia burden, with increased prevalence of factors associated with cognitive decline. Multidomain lifestyle interventions might delay cognitive decline, but populations from Latin America remain under-represented in dementia prevention trials. We aimed to investigate the feasibility of a culturally adapted, multidomain, systematic lifestyle intervention and investigate its effects on global cognitive function in at-risk older adults (aged 60-77 years). METHODS: The LatAm-FINGERS Initiative for Cognitive Change (hereafter referred to as LatAm-FINGERS) was a single-blind, multicentre, randomised clinical trial conducted in 11 Latin American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Peru, and Uruguay). Individuals aged 60-77 years with high risk of dementia (cardiovascular risk factors, ageing, and dementia risk score ≥6), and suboptimal cognitive performance were randomly assigned (1:1) to receive either a 2-year systematic lifestyle intervention (SLI group) or a flexible lifestyle intervention (FLI group). Randomisation was stratified by the study centre to ensure balance and implemented using permuted blocks of eight. Participants and intervention staff were not masked to group assignment, but individuals who assessed outcomes were masked throughout the trial. The SLI provided structured multidomain lifestyle interventions with supervised support and monitoring; FLI offered health advice. Primary outcomes were trial feasibility (evaluated using selected RE-AIM measures: Reach, Implementation, and Maintenance) and the intervention's effects on global cognitive composite trajectories over 2 years (change in the global cognitive composite score over 2 years). This trial is registered at ClinicalTrials.gov (NCT06492967) and has been completed. FINDINGS: Participants were enrolled between Oct 27, 2021, and July 7, 2023; the last participant completed follow-up on Nov 7, 2025. Among 1719 assessed, 1065 participants included in the analytic sample were randomly assigned to the SLI group (n=539) or the FLI group (n=526). Mean age was 67&#xb7;5 years (SD 4&#xb7;7), 795 (75%) of 1065 participants were women, and 270 (25%) were men. Self-reported race and ethnicity were: 624 (59%) Mestizo, 288 (27%) White, 72 (7%) Mulatto, 25 (2%) Mixed or other, 18 (2%) Black, 14 (1%) Indigenous, and 24 (2%) did not report race or ethnicity. 877 (82&#xb7;3%) of 1065 completed the 2-year follow-up. Recruitment effectiveness (Reach) was 62&#xb7;0%; mean adherence to the SLI group (Implementation) was 71&#xb7;6% over the entire trial; and frequencies of complete cognitive outcomes data (Maintenance) were 87&#xb7;9% at 6 months, 85&#xb7;3% at 12 months, 81&#xb7;4% at 18 months, and 84&#xb7;8% at 24 months in the SLI group compared with 86&#xb7;3% at 6 months, 78&#xb7;9% at 12 months, 73&#xb7;4% at 18 months, and 79&#xb7;8% at 24 months in the FLI group. Dropouts were higher in the FLI group than in the SLI group (20&#xb7;2% vs 15&#xb7;2%; p=0&#xb7;042). Global cognitive composite scores increased over time in both groups, with a mean annual change of 0&#xb7;31 SD (95% CI 0&#xb7;28-0&#xb7;34) per year in the SLI group and 0&#xb7;20 SD (0&#xb7;17-0&#xb7;23) per year in the FLI group (mean between-group difference of 0&#xb7;11 SD per year [0&#xb7;06-0&#xb7;15; p<0&#xb7;0001]). Overall, 478 adverse events were reported (412 in the SLI group and 66 in the FLI group). The most common adverse events were musculoskeletal symptoms (113 [21%] in the SLI group, 13 [2%] in the FLI group), upper respiratory infections (50 [9%] in the SLI group, one [<1%] in the FLI group), and COVID-19 infection (31 [6%] events in the SLI group). Serious adverse events occurred in 50 (9%) participants in the SLI group and 24 (5%) participants in the FLI group; none were related to the intervention. There were eight deaths (three in the SLI group and five in the FLI group), and none were related to the intervention. INTERPRETATION: A culturally adapted multidomain lifestyle intervention was feasible across Latin America and resulted in greater cognitive improvements than a flexible health-advice intervention in older adults at risk of cognitive decline. These findings extend the evidence base for multidomain lifestyle interventions to populations historically under-represented in dementia research, supporting their feasibility and scalability as strategies to reduce cognitive decline risk amid the rapidly growing burden of dementia in low-income and middle-income countries. FUNDING: Alzheimer's Association. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.