Non-pharmacological Intervention for Preclinical Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
Alzheimer's disease (AD) is the most common form of neurodegenerative disorders leading to dementia. Currently, there has been no effective drugs targeting this disease. Functional food is considered as a potentially non-pharmacologic treatment. In this project, the investigators aim to investigate the effectiveness of a mixed functional food with main compositions of ginsenoside, green tea polyphenols and marine collagen peptide on cognition for individuals with subjective cognitive decline (SCD). Taking the randomized, double-blind, placebo-controlled method, participants in the functional food group will take mixed functional foods for three months and those in the placebo group will take placebo. After that, the investigators will investigate the changes of cognitive function. Furthermore, based on the neuroimaging technique, the regulatory mechanism of functional food in intervening SCD will be revealed from the perspective of altered brain functional activity. In conclusion, these results are beneficial for understanding the therapeutic effect of mixed functional foods as a non-drug treatment for early AD and further elucidating the potential brain mechanism, which are of great values in solving scientific and clinical practice issues.

Detailed Description
-----------------
Currently, there has been no effective therapy for Alzheimer's disease (AD). Functional food is now considered as a potentially non-pharmacologic intervention and supplementation of functional food may positively affect cognitive function for patients with AD. However, there are few existing studies involving the role of mixed functional foods with multiple compositions on cognition and neuroimaging biomarkers for subjective cognitive decline (SCD). Sixty participants with SCD will be recruited in this three-month, randomized, double-blind, placebo-controlled trial. Each group had thirty participants. Participants in the functional food group will take mixed functional foods for three months and those in the placebo group will take placebo. After that, the investigators will investigate the changes of memory measures, which is the primary outcome. Furthermore, based on the neuroimaging technique of functional near-infrared spectroscopy (fNIRS), the regulatory mechanism of mixed functional foods in intervening SCD will be revealed from the perspective of altered brain functional activity. In conclusion, these results are beneficial for understanding the therapeutic effect of mixed functional foods as a non-drug therapy for preclinical AD and further elucidating the potential brain mechanism, which are of great values in solving scientific and clinical practice issues.

Official Title
-----------------
Effects of Mixed Functional Foods Supplementation on Cognition and Neuroimaging Biomarkers in Adults With Subject Cognitive Decline

Conditions
-----------------
Alzheimer Disease, Functional Food, Subjective Cognitive Decline, Intervention, Neuroimaging

Intervention / Treatment
-----------------
* Dietary Supplement: Mixed functional foods supplementation
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 50-79 years old, right-handed and Mandarin-speaking subjects; self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event; normal age-adjusted, gender-adjusted and education-adjusted performance on standardised cognitive tests; concerns (worries) associated with memory complaint; failure to meet the criteria for MCI or dementia Exclusion Criteria: a history of stroke; major depression (Hamilton Depression Rating Scale score > 24 points); other central nervous system diseases that may cause cognitive impairment, such as Parkinson's disease, tumors, encephalitis and epilepsy; cognitive impairment caused by traumatic brain injury; systemic diseases, such as thyroid dysfunction, syphilis and HIV; a history of psychosis or congenital mental growth retardation.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 79 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed functional foods group with SCD<br>Thirty participants in this group will take mixed functional foods for three months. | Dietary Supplement: Mixed functional foods supplementation<br>* In this project, taking the method of random, double blindness and control, participants in the mixed functional foods group will take functional foods with main compositions of ginsenoside, green tea polyphenols and marine collagen peptide for three months. After that, neuropsychological tests and neuroimaging biomarkers will be compared between functional food group and placebo group.<br>|
| Placebo Comparator: Placebo group with SCD<br>Thirty participants in this group will take placebo for three months. | Dietary Supplement: Placebo<br>* In this project, taking the method of random, double blindness and control, participants in the placebo group will take placebo for three months. After that, cognitive changes and neuroimaging biomarkers will be compared between functional food group and placebo group.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Auditory Verbal Learning Test (AVLT) score | After intervention for three months, the investigators will compare memory changes based on Auditory Verbal Learning Test (AVLT) scale in two groups, in order to investigate the therapeutic effectiveness of mixed functional foods supplementation. The scale of AVLT focuses on the memory domain, especially AVLT-long delayed memory, with cut-off points as 5 (50-59 years old), 4 (60-69 years old), 3 (70-79 years old) and AVLT-recognition, with cut-off points as 20 (50-59 years old), 19 (60-69 years old), 18 (70-79 years old). Higher scores mean a better outcome. | Three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FNIRS-based brain functional activity changes | At baseline and post-intervention visits, the brain functional activity data will be collected using functional near-infrared spectroscopy (fNIRS) technique. The investigators will compare the changes of brain functional activity based on the measure of oxyhemoglobin concentration signal with relatively high signal to noise ratio (SNR) in two groups, in order to reveal the regulatory mechanism of mixed functional foods in intervening SCD persons. | Three months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Subjective cognitive decline, Mixed functional foods, Non-pharmacologic intervention