Remote, lower-intensity, multidomain lifestyle intervention for subjective cognitive decline or mild cognitive impairment (APPLE-Tree): a multicentre, single-masked, randomised controlled trial

Trials of high-intensity, multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aimed to evaluate the effectiveness of a lower-intensity, personally-tailored dementia prevention programme in improving cognition in adults with subjective cognitive decline or mild cognitive impairment. We conducted a single-masked, multisite, randomised controlled clinical trial recruiting older adults with subjective cognitive decline or mild cognitive impairment across 11 sites in England. Participants were randomly assigned (1:1) to the 12-month Active Prevention in People at Risk of Dementia through Lifestyle, Behaviour Change and Technology to build Resilience (APPLE-Tree) intervention or to the control condition (usual care plus brief written information about dementia prevention). Randomisation was blocked and stratified by site, with allocations assigned via a remote web-based system. The intervention promoted healthy lifestyles, social connections, enjoyable activities, and self-management of long-term conditions. It comprised ten 1-h group video-call sessions over 6 months, supplemented with alternating, informal, 40-min video-call sessions (termed tea breaks) and individual goal-setting calls between sessions. From months 6 to 12, participants continued with monthly online tea breaks. The primary outcome was cognition (Neuropsychological Test Battery [NTB] score) at 24 months, analysed using an intention-to-treat approach. This trial was pre-registered with the ISRCTN Registry (ISRCTN17325135); further analyses are ongoing. Between Oct 5, 2020, and Dec 31, 2022, we screened 1287 individuals for eligibility and randomly assigned 746 to the APPLE-Tree intervention (n=374) or control treatment (n=372). There were 177 (47%) women and 194 (52%) men in the intervention group and 173 (47%) women and 198 (53%) men in the control group. The primary outcome analysis included 635 (85%) of 746 participants. Mean NTB scores increased in both groups over time, with greater improvement in the intervention group than in the control group (mean 24-month NTB 0·33 [SD 0·67] vs 0·21 [0·75]; adjusted mean difference 0·06 [95% CI -0·001 to 0·128]; p=0·055). Serious adverse events occurred in 35 (9%) participants in the intervention group and 30 (8%) participants in the control group; none were intervention-related. APPLE-Tree is an accessible intervention associated with small improvements in cognition, although these results were not statistically significant. Low-intensity interventions that can be delivered remotely by non-clinical facilitators have the potential for wide-scale implementation to support adults with memory concerns. However, further work is needed to optimise the intervention for delivery in routine settings. Economic and Social Research Council and National Institute for Health and Care Research programme grant.