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Background: Preventive interventions for dementia are urgently needed and must be tested in randomised controlled trials (RCTs). Selection (volunteer) bias may limit efficacy, particularly in trials testing multidomain interventions and may also be indicative of disparities in intervention uptake in real-world settings. We identified factors associated with participation and adherence in a 3-year RCT of multidomain lifestyle intervention and/or omega-3 supplementation for prevention of cognitive decline and explored reasons for (non-) participation. Methods: Ancillary study during recruitment and follow-up of the 3-year Multidomain Alzheimer Preventive Trial (MAPT) conducted in in 13 memory centres in France and Monaco, involving 1630 community-dwelling dementia-free individuals aged ≥ 70 who were pre-screened for MAPT (1270 participated in MAPT; 360 declined to participate). Results: Response rates were 76% amongst MAPT participants and 53% amongst non-participants. Older individuals (odds ratio 0.94 [95% confidence interval 0.91–0.98] and those with higher anxiety (0.61 [0.47–0.79]) were less likely to participate in the trial. Those with higher income (4.42 [2.12–9.19]) and family history (1.60 [1.10–2.32]) or greater fear (1.73 [1.30–2.29]) of dementia were more likely to participate, as were those recruited via an intermediary (e.g. pension funds, local Alzheimer's associations, University of the 3rd Age, sports clubs) (2.15 [1.45–3.20]). MAPT participants living in larger towns (0.71 [0.55–0.92]) and with higher depressive symptoms (0.94 [0.90–0.99]) were less likely to adhere to the interventions. Greater perceived social support (1.21 [1.03–1.43]) and cognitive function (1.37 [1.13–1.67]) predicted better adherence. Descriptively, the most frequent reasons for accepting and refusing to participate were, respectively, altruism and logistical constraints, but underlying motivations mainly related to (lack of) perceived benefits. Conclusions: Disparities in uptake of health interventions persist in older age. Those most at risk of dementia may not participate in or adhere to preventive interventions. Barriers to implementing lifestyle changes for dementia prevention include lack of knowledge about potential benefits, lack of support networks, and (perceived) financial costs. Trial registration: NCT00672685 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]