Combined mind–body physical exercise, cognitive training, and nurse-led risk factor modification to enhance cognition among older adults with mild cognitive impairment in primary care: a three-arm randomised controlled trial
Authors: Zijun Xu, Dexing Zhang, Benjamin Hon-Kei Yip, Eric Kam-Pui Lee, Paul Kwok-Ming Poon, Ruth Peters, Zuyao Yang, Allen Ting-Chun Lee, Maria Kwan-Wa Leung, Eliza Lai-Yi Wong, Vincent Chung-Tong Mok, Linda Chiu-Wa Lam, Samuel Yeung-Shan Wong
Journal: The Lancet Healthy Longevity (2025)

Mild cognitive impairment is a cognitive state that is worse than that of healthy older adults but less severe than dementia. The effectiveness of a nurse-led risk factor modification (RFM) intervention for older adults with mild cognitive impairment is unclear. The study aimed to compare the effects of: (1) a multi-component intervention: combined cognitive training, mind-body physical exercise, and nurse-led RFM (CPR), (2) nurse-led RFM alone, and (3) health advice alone on cognitive function among older adults with mild cognitive impairment in primary care. We did a 15-month, three-arm, open-label, blinded-endpoint, randomised controlled trial in older adults with mild cognitive impairment at a university-affiliated research and training clinic of the Lek Yuen Health Centre in Hong Kong. Inclusion criteria were age 60-80 years, a Hong Kong Montreal Cognitive Assessment score of 19-25 (defined as mild cognitive impairment), and a physically stable condition. Participants were randomly assigned (1:1:1) via computer-generated allocation sequencing to receive either CPR, RFM, or health advice. Assessors and data analysts were masked to group allocation. Participants randomly assigned to the CPR and RFM groups met the nurse quarterly and the primary care physician every 6 months. The CPR group also received Tai Chi and cognitive training three times a week for 3 months. The health advice group received booklets with general health advice. Assessments were conducted at baseline, 6 months, 12 months, and 15 months. The primary outcome was the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) Z score at 15 months. The analysis followed the modified intention-to-treat principle that included participants completing at least one follow-up assessment. A linear mixed model was used for the analysis, with adjustments for multiple comparisons made using Bonferroni's correction. The trial was preregistered at the Chinese Clinical Trial Registry (ChiCTR 1900026857), and is completed. Between Oct 28, 2019, and Dec 1, 2022, 3122 registrations were received, 1104 were excluded (declined to participate, duplicate registrations, or unable to be contacted), and 2018 were assessed for eligibility. A further 1562 participants were excluded, and 456 participants were randomly assigned to an intervention. 152 participants were assigned to the CPR group, 152 to the RFM group, and 152 to the health advice group. 423 participants who completed at least one follow-up assessment were included in the analysis (139 in the CPR group, 144 in the RFM group, and 140 in the health advice group). 118 (28%) participants were male and 305 (72%) were female. The mean age of participants was 70·1 years (SD 4·9). No significant difference between the three groups in ADAS-Cog was found at the primary endpoint at 15 months (CPR vs health advice, β= -0·04 [95% CI -0·34 to 0·26]; RFM vs health advice, β= -0·14 [-0·44 to 0·15]; CPR vs RFM, β=0·10 [-0·19 to 0·40]) nor at the 6-month and 12-month follow-ups. New interventions for patients with mild cognitive impairment on top of health advice should be recommended only when they have been refined and evaluated to be effective by future trials. Health and Medical Research Fund.