Shanghai Non-pharmacological Intervention of Mild Cognitive Impairment

Study Overview
=================
Brief Summary
-----------------
This study evaluates the effects of computerized cognitive training and cognitive training plus exercise training on different cognitive domains in mild cognitive impairment (MCI) patients. Patients will be randomized into the computerized training group, cognitive training plus exercise training group and the control group.

Detailed Description
-----------------
Mild cognitive impairment (MCI) is an early stage of Alzheimer Disease (AD). Increasing evidence has indicated that cognitive trainings improve cognition functions of MCI patients in multiple cognitive domains, making it a promising therapy for MCI. However, the effect of long-time training has not been widely explored. It is also necessary to evaluate the extent of its function in reducing the conversion rate from MCI to AD.

Official Title
-----------------
Shanghai Non-pharmacological Intervention of Mild Cognitive Impairment for Delaying Progress With Longitudinal Evaluation

Conditions
-----------------
Cognitive Dysfunction

Intervention / Treatment
-----------------
* Behavioral: Online cognitive training
* Behavioral: Cognitive training plus physical exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged 50-85; MCI diagnosed according to the National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups[1]; 24≤Mini-Mental State Examination (MMSE) ≤28； The Hamilton Depression Scale/17-item (HAMD) score ≤10; Not on medication for dementia; MRI T2 weighted image (T2WI) scan: aged ≤70 , Fazeca scale for White Matter lesions rating level≤1; >70 years, white matter damage rating scale ≤2. The number of lacunar infarcts larger than 2 cm in diameter ≤2. No infarcts in hypothalamus, entorhinal cortex, para-hypothalamus, cortical and subcortical cavity infarction near gray matter nuclei. The medial temporal lobe atrophy (MTA) score: Grade II or above. Accompanied by reliable caregivers (at least intensive contact of 4 days every week and 2 hours every day) who are expected to participate in the follow-up visits and provide useful information for scores of scales like ADCS-ADL; Education level: primary school (grade 6) or above. Expected good compliance with the therapy and follow-up. Each patient gives a written informed consent, and the study has been approved by Ruijin Hospital's ethical committees. Exclusion Criteria: Cognitive decline caused by other diseases (cerebrovascular disease, central nervous system infections, Parkinson's disease, metabolic encephalopathy, intracranial space-occupying lesions, deficiency of folic acid/vitamin B12 and hypothyroidism); Medical history of other neurological disorders (including stroke, Neuromyelitis optica, Parkinson's disease, epilepsy, etc.); Psychiatric disorders defined by (Diagnostic and Statistical Manual of Mental Disorders) DSM-IV criteria; Unstable or severe disease of heart, lung, liver, kidney or hematopoietic system; History of alcohol or drug abuse; Participation in other clinical trial less than 30 days before the screening of this study; Inability to complete the study.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: online cognitive training<br>Patients will receive 3-4 times of 20-30 minutes' training game every week | Behavioral: Online cognitive training<br>* A variety of cognitive domains will be involved in the training including memory, calculation, attention, visuospatial and executive skills. The difficulty level of each game will be adjusted automatically according to patients' last training results so that patients' correction rate will be kept between 70% and 80%.<br>|
| No Intervention: no training<br>Patients will not undergo preoperative cognitive training. | |
| Experimental: Cognitive training and physical exercise<br>Patients will receive 3-4 times of 20-30 minutes' training game every week and 2 times of 60 minutes' Tai Chi Training | Behavioral: Cognitive training plus physical exercise<br>* Online cognitive training A variety of cognitive domains will be involved in the training including memory, calculation, attention, visuospatial and executive skills. The difficulty level of each game will be adjusted automatically according to patients' last training results so that patients' correction rate will be kept between 70% and 80%. Physical Exercise Tai Chi Training：a teacher will give two 60-min lessons per week. Participants will play Tai Chi in the lessons, following teacher's instruction.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AD | The 3-year incidence of AD in each group will be compared. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The global cognitive function of MCI patients | Alzheimer disease assessment scale (ADAS-Cog) will be used to assess the global cognitive performance of MCI patients | 6 months | 
| Memory | Memory will be assessed using the Auditory verbal learning test-Huashan version (AVLT-H). | 12 months | 
| Attention | Attention will be evaluated by Trial Making Test (TMT). | 12 months | 
| Executive functions | Executive functions will be evaluated by the Stroop task. | 12 months | 
| Language | Language will be assessed by Boston naming test (30-item version). | 12 months | 
| Visual spatial ability and visual memory | Visual spatial ability and visual memory will be evaluated by the Rey-Osterrieth complex figure test (CFT). | 12 months | 
| Activities of daily living | Activities of daily living will be assessed by Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). | 6 months | 
| Structural MRI | Volume of hippocampus and other specific brain regions | 12 months | 
| Gut microbiota | Number of genera and abundence of E.coli in feces and blood | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mild cognitive impairment