Effects of eligibility criteria on patient selection and treatment implications from 10 multidomain dementia prevention trials: a population-based study

Introduction: Dementia prevention trials have so far shown little benefit of multidomain interventions against cognitive decline. Recruitment strategies in these trials often centre around dementia risk or cardiovascular risk profile, but it is uncertain whether this leads to inclusion of individuals who may benefit most from the intervention. We determined effects of eligibility criteria on recruitment of potential trial participants in the general population. Methods: In a systematic search until January 1, 2022, we identified all published and ongoing large (>= 500 participants), phase-3 multidomain trials for the prevention of cognitive decline or dementia. We applied trial eligibility criteria to 5381 participants of the population-based Rotterdam Study (mean age: 72 years, 58% women), to compare participant characteristics, predicted risk of cardiovascular disease and dementia risk, between trial eligible and ineligible persons. Results: We identified 10 trials, of which 5 had been published (DR's EXTRA, FINGER, preDIVA, MAPT and HATICE), and 5 are ongoing (US-POINTER, MIND-CHINA, MYB, AgeWell.de and J-Mint). Among all Rotterdam Study participants, eligibility across published trials ranged from 48% for MAPT to 87% for preDIVA, in line with original trial reports. Variability in eligibility was wider for ongoing trials, from 1% for US-POINTER to over 94% for MYB-trial. Over 70% of trial eligible individuals are recommended preventive intervention in routine care based on their cardiovascular risk, similar for lipid-lowering (71%) and blood pressure-lowering treatment (73%). Ten-year risks of dementia were similar for eligible compared to ineligible individuals (12 versus 11%). Conclusion: Multidomain dementia prevention trials fail to preferentially include those at highest risk of dementia, and mostly include individuals who qualify for interventions already on the basis of cardiovascular prevention guidelines. These findings call for better targeted enrolment of individuals for whom trial results can improve clinical decision making.

Automated summary

Multidomain dementia prevention trials fail to prioritize high-risk dementia patients, and mostly include individuals who already meet cardiovascular prevention guidelines. Better targeting of recruitment for individuals whose trial results can improve clinical decision making is needed.