The Effects of COgNitive Training in Community-dwelling Older Adults at High Risk for demENTia (CONTENT): study protocol of two double-blind, randomized, placebo-controlled trials

Introduction

Dementia contributes to the disease burden worldwide, and people with hypertension or type 2 diabetes are associated with an elevated risk of developing dementia. It is essential to prevent or delay cognitive decline in people at high risk within the community. Our trials aim to evaluate the effects of adaptive cognitive training on community-dwelling older adults with hypertension or type 2 diabetes but no dementia.

Method and analysis

Two multicenter, double-blind, randomized, placebo-controlled trials, named COgNitive Training in community-dwelling older adults at high risk for demENTia and with Hypertension (CONTENT-Hypertension) and COgNitive Training in community-dwelling older adults at high risk for demENTia and with Diabetes (CONTENT-Diabetes), will be conducted to investigate the effects of adaptive cognitive training on participants aged 60 years or above who have been diagnosed with hypertension or type 2 diabetes but no dementia. Each trial will enroll 120 participants. Participants will be recruited from local community in Shijingshan and Haidian District, Beijing, and allocated to either the intervention or control group using a 1:1 ratio. The intervention group will engage in 12 weeks of adaptive cognitive training, while the control group will receive 12 weeks of placebo cognitive training. A 24-week follow-up assessment will be conducted for all participants to evaluate the persistency of the effects. The primary outcome is the 12-week change in Montreal Cognitive Assessment (MoCA) Basic scores from baseline to the end of the intervention (12 weeks). Secondary outcomes include 6-week and 24-week changes in the MoCA from baseline; 6-week, 12-week, and 24-week changes in Trail Making Test-A&B (TMT-A, TMT-B), Digit Symbol Substitution Test (DSST), the World Health Organization/University of California at Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT), and Boston naming test (BNT) scores of cognitive functions; 6-week and 12-week changes in Geriatric Depression Scale (GDS), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh sleep quality index (PSQI); and 12-week change in blood pressure (CONTENT-Hypertension) or fasting blood glucose and HbA1c (CONTENT-Diabetes) from baseline.

Ethics and dissemination

This study will adhere to the ethical principles outlined in the Declaration of Helsinki and comply with international standards for Good Clinical Practice (GCP). All participants will sign the informed consent at baseline. This study has been approved by the Ethics Committee of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (approval numbers: 2023-139 and 2024-162). The findings of the trials will be disseminated through publications in peer-reviewed scientific journals and presented at academic conferences.

Trial registration numbers

NCT06512922 and NCT06524388 .

STRENGTHS AND LIMITATIONS OF THIS STUDY

• Both trials are double-blind, randomized, placebo-controlled trials to investigate the effects of adaptive cognitive training among patients with hypertension or type 2 diabetes but no dementia. The rigorous randomized control trial design can ensure the reliability and efficacy of the trial.

• Adaptive cognitive training will automatically target the most impaired cognitive domains (domain-adaptive). The difficulty of cognitive training tasks will upgrade to the next level once the participants reach a high accuracy of 80% (difficulty-adaptive), which enables targeted and efficient training.

• The use of placebo cognitive training can reduce the impact of the placebo effect on the results.

• All training will be conducted remotely, allowing participants to complete the program from their homes to increase convenience and participant compliance.