Relationship Between Gut Microbiome, Probiotics, and Mild Cognitive Impairment

Study Overview
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Brief Summary
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This study is to evaluate whether the consumption of probiotics can improve the symptoms of patients with mild cognitive impairment; also evaluate the effects of probiotics on patients' blood, oxidation and stress related indicators.

Detailed Description
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Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. It can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes. Probiotics are regarded as active microorganisms. When consumed in sufficient amounts, participants can regulate intestinal flora, intestinal permeability, inflammation and antioxidant reactions in the body, and may produce host health, including delaying disease and regulating metabolic disease progression and prevent complications.

Official Title
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Relationship Between Gut Microbiome, Probiotics, and Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment (MCI)

Intervention / Treatment
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* Dietary Supplement: PS23 live
* Dietary Supplement: PS23 heat-treated
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who is suffering from Mild Cognitive Impairment. Clinical Dementia Rating (CDR) 0.5. Age 40-80 and willing to sign the Informed Consent. Education level is above the junior high school level. Healthy control who is eligible judged by PI. Exclusion Criteria: Patients on antibiotics within the preceding one month. Patients using of other probiotic products (sachet, capsule or tablet) within the preceding two weeks. Have undergone surgery of liver, bladder, or gastrointestinal tract. Have current or history of inflammatory bowel disease. Have history of cancer. Known allergy to probiotics. Dementia (MMSE ≤ 23). Cognitive Impairment caused by head injury. History of cerebral apocalypse. Other possible diseases may cause cognitive impairment, such as: Parkinson's disease, cervical mass, hydrocephalus or epilepsy. Severely depressed patients (sick person health questionnaire-9 (PHQ-9) ≥ 20). Severe anxiety patients (Generalized Anxiety Dosorder 7-Item (GAD-7) ≧ 15). Undergoing medication treatment for acute illness, Organic psychosis or diagnosed as psychiatric illness within 3 months or poor control of chronic psychiatric illness. Undergoing parenteral nutrition. Not eligible judged by PI.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participates in three groups, 60 patients in each group. One group of patients will be given PS23, one will be given heat-treated PS23 and the other one will be given placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PS23<br>The PS23 belongs to Lactobacillus paracasei group, 2 caps daily use. | Dietary Supplement: PS23 live<br>* PS23 belongs to Lactobacillus paracasei group.Probiotic capsules contain 30 billion CFU (colony forming units) of PS23<br>|
| Experimental: heat-treated PS23<br>PS23 heat-treated, 2 caps daily use. | Dietary Supplement: PS23 heat-treated<br>* The PS23 heat-treated probiotic capsule contain 30 billion of PS23 cells.<br>|
| Placebo Comparator: placebo<br>The placebo capsule contains microcrystalline cellulose, 2 caps daily use. | Dietary Supplement: Placebo<br>* The placebo capsule contains microcrystalline cellulose.<br>|
| No Intervention: Healthy Control<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State Examination, MMSE (end point scare-baseline score)/ Baseline score*100% ≥ 12% | The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function, The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills. | From Baseline to 12 Weeks Assessed | 
| Wechsler Memory Scale-III, WMS-III (end point scare-baseline score)/ Baseline score*100% ≥ 12% | The WMS-III has most representative standardization databases to assess memory and make optimal clinical recommendations. The 11 subtests that comprise the index scores average 60 min, ranging from 45 to 75 min, to administer. The time needed to administer the 13 subtests required to generate all of the summary and index scores is 80 min, with a range of 65 to 95 min. | From Baseline to 12 Weeks Assessed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Abilities Screening Instrument, CASI | The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment, higher scores mean a better outcome. | From Baseline to 12 Weeks Assessed | 
| Change in Clinical Dementia Rating (CDR) | The CDR is a global summary measure designed to identify the overall severity of dementia. Six different content areas are rated individually (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care). CDR is calculated on the basis of testing six different cognitive and behavioral domains such as memory, orientation, judgment and problem solving, community affairs, home and hobbies performance, and personal care. The CDR is based on a scale of 0-3: no dementia (CDR = 0), questionable dementia (CDR = 0.5), MCI (CDR = 1), moderate cognitive impairment (CDR = 2), and severe cognitive impairment (CDR = 3). | From Baseline to 12 Weeks Assessed | 
| Change in Insomnia Severity Index, ISI | The ISI is a rating tool used to gauge of sleeping. Higher values represent a worse outcome. A 5-point Likert scale is used to rate each item (e.g., 0 = no problem; 4 = very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28). | From Baseline to 12 Weeks Assessed | 
| Change in Geriatric Depression Scale, GDS | The Geriatric Depression Scale (GDS) is a self-report measure of depression in older adults. Users respond in a Yes/No format. The GDS was originally developed as a 30-item instrument. Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression. | From Baseline to 12 Weeks Assessed | 
| Change in Hamilton Anxiety Scale, HAM-A | The HAM-A was one of the first rating scales developed to measure the severity of anxiety symptoms, and is still widely used today in both clinical and research settings. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | From Baseline to 12 Weeks Assessed | 
| Change in The Quality of Life, Enjoyment, and Satisfaction Questionnaire-16, QLESQ-16 | The Quality of Life, Enjoyment, and Satisfaction Questionnaire-16 is a valid, reliable self-report instrument for assessing quality of life. The minimum raw score on the Q-LES-Q-16 is 14, and the maximum score is 70, higher scores mean a better outcome. | From Baseline to 12 Weeks Assessed | 
| Change in Visual Analogue Scale for GI symptoms (VAS-GI) | Visual Analogue Scale for GI symptoms, VAS-GI (visual analogue scale, VAS 0-10) was designed to measure the response of symptoms and well-being in patients after taking PS23, total score is 0-100, higher scores mean a worse outcome. | From Baseline to 12 Weeks Assessed | 
| Change in Color Trails Test (CTT) | Color Trails Test (CTT) is developed to be free from the influence of language and cultural bias, the CTT assesses sustained attention in adults. | From Baseline to 12 Weeks Assessed | 
| Change in levels of exploratory blood-based biomarkers for inflammatory and/or oxidative stress changes | Blood-based biomarkers (e.g. IL-6, TNF-α, GDF-15, Adiponectin, EGF, BDNF, MDA, Nitric oxide (NO) , GSH, TAC, Ghrelin, Cystatin C , Hs-CRP, HbA1c, Glucose (AC), Triglycerides (TG), LDL, HDL , Insulin, miRNA and total cholesterol ) | From Baseline to 12 Weeks Assessed | 
| Change in Gut microbiome | The gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. Stool will be examined before and after probiotics. | From Baseline to 12 Weeks Assessed | 
| Change in WAIS-IV | WAIS-IV is composed of 10 core subtests and five supplemental subtests, with the 10 core subtests yielding scaled scores that sum to derive the Full Scale IQ. With the WAIS-IV, the verbal/performance IQ scores from previous versions were removed and replaced by the index scores. | From Baseline to 12 Weeks Assessed |