CEEEC-II: A 12-Week Physical and Cognitive Enrichment Extension Study in Older Stroke Survivors With Multimorbidity

CEEEC-II is the prospective, open-label extension of the CEEEC Phase I 2×2 factorial cluster-randomized trial (NCT06975501). The extension is conducted in 32 community health service stations in Kunshan, Jiangsu Province, China. Up to 420 participants who completed the Phase I endpoint assessment will be approached consecutively. The estimated Phase II enrollment is 356 participants, with a target of at least 320 participants completing the primary endpoint assessment. All participants will undergo a new eligibility review and provide written informed consent specifically for CEEEC-II.

No new randomization will occur. Each participating community health service station will retain its Phase I cluster assignment: physical and nutrition enrichment only, AI-enabled cognitive enrichment only, combined physical, nutrition, and cognitive enrichment, or usual community-based care. This preserves the original 2×2 factorial structure while recognizing that the Phase II cohort is a selectively re-consented extension cohort rather than a newly randomized sample.

Each participant will receive 12 weeks of the intervention assigned to the community cluster. The active program comprises eight physician-led Vitality Camp sessions and four volunteer-led reinforcement activities. The upgraded physical and nutrition component integrates age-appropriate aerobic, resistance, balance, and flexibility exercises, incorporates Baduanjin-based movements, and provides practical nutrition education. The upgraded cognitive component combines health education with age-adapted, AI-enabled large-screen interactive games designed to engage memory, attention, processing speed, visuospatial ability, and executive function. Reinforcement activities and take-home materials support continued participation and practice between group sessions. Participants in the usual-care arm continue routine community-based stroke and chronic disease management without the structured Phase II physical or cognitive enrichment program.

Assessments will be conducted at baseline and approximately 12 weeks after intervention initiation. The primary outcome is an intrinsic capacity composite score derived from cognition, locomotion, vitality, and psychological capacity domains. The primary estimand is the marginal effect of the cognitive enrichment factor. The physical enrichment factor effect is a key secondary estimand. Cognitive function measured with the Montreal Cognitive Assessment is retained as a secondary outcome in continuity with Phase I. Other prespecified outcomes include MemTrax performance, physical function, nutritional status, depressive symptoms, blood pressure, health-related quality of life, medication adherence, physical activity, activities of daily living, falls, hospitalization, and recurrent stroke. Analyses will account for community-level clustering and the original factorial assignment.

Inclusion criteria

• Completed the endpoint assessment of the preceding CEEEC Phase I trial (NCT06975501) and remains under management at a participating community health service station in Kunshan.
• Age 60 years or older.
• Hospital-confirmed ischemic or hemorrhagic stroke in a stable stage, with no new or worsening neurological deficit within the previous 3 months.
• Registered hypertension and/or type 2 diabetes mellitus; other comorbid conditions are permitted.
• Willing and able to participate in the 12-week community-based extension program and complete baseline and endpoint assessments.
• Able to travel to the community site independently or with a cane or walker; not dependent on a wheelchair for attendance.
• Short Physical Performance Battery total score >=3, or able to maintain a supported side-by-side standing position for 10 seconds when the total score is <3.
• Able to communicate in Mandarin Chinese or the Kunshan dialect and able to recognize Arabic numerals.
• Corrected vision sufficient to identify large characters at approximately 40 cm and at least one upper limb able to complete touchscreen selection.
• Resides in the participating community and has no plan to move away during the study period.
• Provides written informed consent specifically for CEEEC-II.

Exclusion criteria

• Life-threatening disease or another condition associated with an expected survival of less than 6 months.
• A new stroke, transient ischemic attack, acute coronary event, or hospitalization for decompensated heart failure within the previous 3 months.
• Uncontrolled resting blood pressure (systolic >=180 mmHg or diastolic >=110 mmHg after repeated measurement) until clinically reassessed and controlled.
• Extreme glycemic instability, including fasting blood glucose >16.7 mmol/L or severe hypoglycemia requiring assistance within the previous month, until clinically reassessed.
• An absolute contraindication to unsupervised community exercise or another medical condition judged by the study clinician to make participation unsafe.
• Unable to walk to the community site even with a cane or walker, or dependent on a wheelchair for attendance.
• A severe musculoskeletal, neurological, visual, hearing, cognitive, psychiatric, or communication impairment that prevents safe participation or valid completion of study procedures.
• Unable to recognize Arabic numerals or unable to complete touchscreen selection with either upper limb.
• Current participation in another structured physical, cognitive, or nutrition intervention study that may contaminate the assigned intervention.
• Any other reason documented by the study clinician as making the individual unsuitable for participation.