Shanghai Non-pharmacological Intervention for Mild Cognitive Impairment and Mild Alzheimer's Disease

Study Overview
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Brief Summary
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This study is a multicentre, randomized, double-blind, controlled trial that aims to investigate the efficacy of multi-domain life-style intervention including low inflammatory-index diet, exercise, and cognitive training in patients with mild cognitive impairment and mild Alzheimer's disease.

Detailed Description
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This is a multicentre, randomized, double-blind, controlled trial that aims to investigate the efficacy of multi-domain life-style intervention including low inflammatory-index diet, exercise, and cognitive training in patients with mild cognitive impairment and mild Alzheimer's disease. Patients who eligible to the inclusion criteria and ineligible to the exclusion criteria will be randomly assigned into three groups by a 1:1:1 ratio. Patients in first arm will receive multi-domain life-style intervention including low inflammatory-index diet, exercise, and cognitive training. Patients in the second arm will receive intervention of exercise and cognitive training. Patients in the third arm will receive regular health advice. We hypothesize that the multi-domain intervention will reduce impairment in the study group compared to the control group during the 2-year intervention period.

Official Title
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Shanghai Non-pharmacological Intervention for Mild Cognitive Impairment and Mild Alzheimer's Disease: Combined Low Inflammatory-index Diet, Physical Exercises, and Cognitive Training in Nursing Home

Conditions
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Mild Cognitive Impairment, Mild Dementia

Intervention / Treatment
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* Behavioral: Diet intervention
* Behavioral: Exercise
* Behavioral: Cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 60-90 years In accordance with the diagnostic criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease from the National Institutes of Health National Institute on Aging-Alzheimer's Association (NIA-AA) (2011) The Hamilton depression rating scale/17 edition (HAMD) total score≤10 Neurological examination: no obvious signs Education: primary school (grade 6) or above and capacity to complete tests for cognitive ability Capacity to give consent Exclusion Criteria: Other causes of cognitive decline: cerebrovascular disease, central nervous system infection, Creutzfeldt-Jakob disease, Huntington's and Parkinson's disease, Creutzfeldt-Jakob disease, traumatic brain dementia, other physical and chemical factors (such as drugs, alcohol, CO), systemic disease (hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial occupation (a subdural hematoma, brain tumor), the endocrine system disease (thyroid disease, parathyroid disease), and vitamins deficiency or any other causes of dementia The history of nervous system diseases, including stroke, optic myelitis, Parkinson's disease, epilepsy, etc Psychiatric patients, including schizophrenia or other mental illnesses, bipolar disorder, major depression, or delirium There are unstable or serious heart, lung, liver, kidney, endocrine, and hematopoietic system diseases, or Poor prognosis because of malignant diseases such as tumors. Vision or hearing problems that lead to poor performance on cognitive tests Two years history of severe alcoholism, and drug abuse Participants who participated in any other trial 30 days prior to their screening visit Contraindication of MRI scanning Special requirements for diet, e.g., allergy to common food or on a special diet due to medical needs Participants who cannot be followed for at least 6 months (due to a health situation or migration)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-domain intervention group<br>Patients in this arm will receive multi-domain life-style intervention including low inflammatory-index diet, exercise, and cognitive training. | Behavioral: Diet intervention<br>* Low inflammatory-index diet<br>Behavioral: Exercise<br>* Guided muscle strength training and stretching exercises<br>Behavioral: Cognitive training<br>* Cognitive training will be implemented in person<br>|
| Experimental: Exercise and cognitive training<br>Patients in this arm will receive the intervention of exercise and cognitive training. | Behavioral: Exercise<br>* Guided muscle strength training and stretching exercises<br>Behavioral: Cognitive training<br>* Cognitive training will be implemented in person<br>|
| No Intervention: Standard health counseling at baseline<br>Patients in this arm will have their habitual diet and life style. No particular intervention or consultation would be provided. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline global cognitive function at one year | Change from baseline general cognitive performance at one year assessed by Mini-mental state examination (MMSE) | One year | 
| Change from baseline memory at one year | Change from baseline verbal memory using the Auditory verbal learning test (AVLT) | One year | 
| Change from baseline visual spatial ability and visual memory at one year | Change from baseline visual spatial ability and visual memoryevaluated by the Rey-Osterrieth complex figure test (CFT) | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cognition assessed by Clock drawing test, Symbol-digit test, Trail making test, Boston naming test and Language fluency test | Executive function | One year | 
| Changes in hippocampus related neural circuit-specific resting-state connectivity (FC) | Neural connectivity by functional MRI | One year | 
| Changes in structural brain MRI including volume of hippocampus and other specific brain regions | Brain structure by MRI | One year | 
| Changes in Inflammatory biomarkers | Serum interleukins and tumor necrosis factors | One year | 
| Changes in gut microbiota | Number of genera and abundance of microbiota in feces and blood | One year | 
| Changes in Metabolic biomarkers | Low-density lipoprotein, high-density lipoprotein, and total cholesterol | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild cognitive impairment, Alzheimer's disease, Diet, Physical exercise, Cognitive training