Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease

This is an assessor-blinded, randomized controlled trial. A total of 188 older adults aged 60-85 years with early/mild Alzheimer's disease (AD) will be recruited from care and attention homes for the elderly and elderly activity centres. They will be randomly assigned to receive least acupressure control (LAC, n = 94) and Comfy Acupressure for the Elderly (CAE, n = 94), administered by caregivers (i.e., trained research assistants), for 3 sessions a week for 12 months. The primary outcome is the change in the Montreal Cognitive Assessment, Hong Kong version (HK-MoCA) score from baseline. The secondary outcomes include functional independence, psychological well-being, sleep quality, and health-related quality of life. The outcomes will be assessed at baseline and once bimonthly thereafter, totalling 7 sessions. A linear mixed-effect model will be applied to compare the primary and secondary outcomes. Three blood samples will be collected at baseline, 6 months, and 12 months, respectively, and the baseline blood sample will be immediately measured for the measurement of plasma Aβ42, Aβ40, p-tau181, and p-tau217, blood glial fibrillary acidic protein (GFAP) and neurofilament light chain protein (NfL). Two-way repeated measures analysis of variance (ANOVA) will be used to detect significant differences in blood biomarkers between the two groups. Linear regression will be conducted to examine inter-correlations between clinical outcomes and biomarker levels. Health and social care resource use will additionally be recorded at baseline, 6 months, and 12 months for the economic evaluation to examine the cost-effectiveness of the CAE intervention compared with LAC.

Inclusion Criteria: * have at least one of the following abnormal plasma amyloid and tau levels: Aβ42/Aβ40 ratio ≤ 0.17, p-tau217 \> 0.15 pg/ml, or/and p-tau181 \> 3.3 pg/ml * have mild neurocognitive disorder with the Montreal Cognitive Assessment, Hong Kong version (HK-MoCA) in classifying mild neurocognitive disorder, in which mild neurocognitive disorder is defined as those whose HK-MoCA score falls between the 16th and 2nd percentile of his/her peers adjusted for age and education Exclusion Criteria: * show moderate-to-severe dementia, as evidenced by a HK-MoCA score falling below the 2nd percentile of his/her peers adjusted for age and education * cannot proficiently communicate due to language function impairment * have severe skin lesions on acupressure areas * had a surgery on the head or neck * have a medical condition that is a contraindication for acupressure.