Effects of an Exercise Snacking Intervention on Cognitive Function in Patients With Mild Cognitive Impairment: A Nationwide Multicenter Randomized Controlled Trial

Inclusion criteria

• Aged 51 to 80 years, inclusive.
• Meet the NIA-AA core clinical criteria for probable amnestic mild cognitive impairment (aMCI), including all of the following:

• A self-reported and/or informant-reported history of progressive memory decline lasting for more than 6 months, confirmed by a study neurologist;
• Objective impairment in one or two cognitive domains on standardized neuropsychological testing, with memory impairment required;
• Montreal Cognitive Assessment (MoCA) score of 18-26;
• Cognitive impairment does not result in significant functional dependence, with instrumental activities of daily living (IADL) remaining normal or only mildly impaired;
• Does not meet diagnostic criteria for any type of dementia.
• Able to independently use a smartphone and complete online check-ins, questionnaires, and other digital assessment tasks.
• Able to walk independently without assistance.
• No absolute contraindications to exercise, as determined by the Physical Activity Readiness Questionnaire or by a study physician when exercise-related risks are considered manageable.
• Willing and able to provide written informed consent.
• A primary caregiver, if applicable, is informed of and supportive of study participation.
• Willing and able to comply with the 24-month follow-up schedule and complete all study assessments and intervention tasks.
• Participants taking cognition-enhancing or other cognition-active medications may be included, provided that the medication dose has remained stable for at least 1 month before screening.

Exclusion criteria

• Cognitive impairment attributable to other causes, including:

• Meeting clinical diagnostic criteria for Alzheimer's disease or another type of dementia;
• Cognitive impairment primarily attributable to another clearly identified condition, including neurodegenerative diseases (e.g., Parkinson's disease, Huntington's disease, progressive supranuclear palsy, or multiple sclerosis), severe psychiatric disorders (e.g., schizophrenia, bipolar disorder, or major depressive episode with psychotic features), or systemic diseases (e.g., uncontrolled thyroid dysfunction or vitamin B12 deficiency).
• Severe or unstable medical conditions, including any of the following:

• Acute cardiovascular or cerebrovascular event within the previous 6 months, including myocardial infarction, unstable angina, stroke, or transient ischemic attack;
• New York Heart Association (NYHA) class III or IV heart failure;
• Poorly controlled hypertension, defined as resting blood pressure ≥180/110 mmHg;
• Poorly controlled diabetes mellitus, defined as HbA1c >9.0%;
• Severe musculoskeletal disease resulting in inability to walk continuously for more than 100 meters;
• Severe respiratory disease;
• Malignancy with an estimated life expectancy of less than 2 years.
• Severe visual or hearing impairment that prevents the participant from adequately seeing assessment materials or hearing instructions despite the use of conventional corrective devices, such as glasses or hearing aids.
• High risk of falls, defined by any of the following:

• Two or more unprovoked falls during the previous year;
• A score of 0 on the balance component of the Short Physical Performance Battery (SPPB), indicating inability to stand with the feet together;
• Requirement for routine use of a walking aid or wheelchair.
• Current participation in another clinical trial that may affect cognitive function or physical activity.
• Planning to relocate outside the study area for more than 3 months during the next 24 months.
• Any other condition that, in the investigator's judgment, may compromise participant safety, data integrity, or adherence to the study protocol.