Clinical efficacy of Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention digital therapeutic in patients with mild cognitive impairment: a three‐arm, randomized controlled trial

Background Despite lacking effective pharmacological therapeutic to delay the progression of mild cognitive impairment (MCI) to dementia, accumulative evidence showed that multi‐domain intervention including cognitive training, exercise, diet, etc., is an effective approach. With miscellaneous audio and visual stimuli, emerging digital therapeutic can be incorporated into the multi‐domain intervention and enhance the effect of cognitive interventions. This study adopted the Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention system to develop the BBRT‐online digital therapeutic (BBRT‐online, Figure 1) and will verify the efficacy of both BBRT and BBRT‐online on older patients with MCI. Method This study is a 2‐year, three‐arm, randomized controlled trial, intended to recruit 438 patients with MCI aged 50‐75, with 6 years of education or more, and no neurological disorders or other serious systemic diseases. The participants will be randomly assigned into the BBRT‐online intervention group (n = 200), BBRT intervention group (n = 38), or control group (n = 200). The control group will receive regular health education as the other two groups. Five BBRT‐online training units a day, 15 minutes at least, will execute remotely in the BBRT‐online group. Participants in the BBRT group will attend face‐to‐face BBRT cognitive training twice a week, 1 hour for each at least. Both intervention groups will receive intervention for 12 months and be followed up until the 24th month to assess the persistence of efficacy (Figure 2). Result Primary outcome of this study will be the ACE‐III total score. Secondary outcomes will include 1) neuropsychological scale scores including the MOCA‐B scale, NPI scale, AVLT scale, STT scale, BNT test, and SCS intelligent voice‐based cognitive assessment. 2) Biomarker outcomes: Aβ42, T‐tau, and P‐tau. 3) Neuroimaging outcomes. All participants will meet the research nurse at baseline, and at 6, 12, 18, and 24 months for outcome measurements. This study has been registered in the China Clinical Trials Registry (ChiCTR2200065212). Conclusion BBRT and BBRT‐online have been widely commercialized. This study will systematically evaluate the clinical effectiveness of both BBRT and BBRT‐online for Chinese MCI patients and provide insights into non‐pharmacological intervention mechanisms for improving cognitive function.