Can Lifestyle Changes Reverse Early-Stage Alzheimer's Disease

Study Overview
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Brief Summary
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The objective of this study is to determine if comprehensive lifestyle changes may slow, stop, or reverse the progression of early-stage Alzheimer's disease.

Detailed Description
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51 patients who have early Alzheimer's disease (MoCA above 17) in the San Francisco Bay area were enrolled over time and are randomly assigned to one of two groups. After baseline testing, the first group then receives this lifestyle medicine program for 20 weeks, four hours/day, three days/week (all done virtually via Zoom since March 2020 due to COVID-19). The second group will not receive the lifestyle program for 20 weeks and will serve as a randomized control group during this phase of the study. Both groups will be re-tested after 20 weeks. Then, the second group will cross over and receive this lifestyle medicine program for 20 weeks and the first group will continue the lifestyle program for 20 additional weeks. After a total of 40 weeks, both groups will be re-tested again and compared. Those initially randomly assigned to the control group will receive the intervention for 40 weeks and then be re-tested at that time.

Official Title
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Lifestyle Intervention for Early Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Behavioral: Lifestyle medicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current diagnosis of mild dementia or mild cognitive impairment due to Alzheimer's disease/process (McKhann and Albert criteria), with MoCA score above 17 (i.e., 18 or higher) Willingness and ability to participate in all aspects of the intervention Availability of spouse or caregiver who can provide collateral information and assist with study adherence Exclusion Criteria: severe dementia physical disability that precludes regular exercise clear evidence for other causes of neurodegeneration or dementia, e.g., severe cerebrovascular disease, Parkinson's disease significant ongoing psychiatric or substance abuse problems

Ages Eligible for Study
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Minimum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: In this randomized crossover design, 51 patients with early Alzheimer's disease were randomly-assigned to one of two groups. After baseline testing, the first group receives the lifestyle program for 20 weeks (via Zoom since 2/20 due to COVID-19). The second group does not and is a randomized control group during this phase. Both groups are re-tested after 20 weeks. Then, the second group crosses over and receives this program for 20 weeks and the first group continues the program for 20 additional weeks. After 40 weeks, both groups are re-tested again. Patients initially randomly assigned to the control group will receive the intervention for a total of 40 weeks and then be re-tested. Due to challenges in recruiting patients, including Covid-19, we recently terminated recruitment after 51 patients were recruited. This decision was based on recruitment and funding issues, without review of any of the data. This trial will continue until all 51 patients have completed it.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental (Intervention) Group<br>These patients will receive the comprehensive lifestyle medicine intervention from day 1 through the end of the study. They will be tested at baseline, after 20 weeks, and after 40 weeks. | Behavioral: Lifestyle medicine<br>* Diet: A low fat (10-15%) whole foods vegan diet, high in complex carbs and low in refined carbs (fruits, vegetables, whole grains, legumes, soy, seeds & nuts). Calories unrestricted. Multivitamin, fish oil, curcumin, vitamin C, B12, CoQ10, lion's mane, probiotic, and magnesium. 21 meals/week and supplements provided to participants and caregivers at no cost to them. Exercise: Aerobic (e.g., walking) and strength training 30 minutes/day based on a personalized prescription from an exercise physiologist or certified personal trainer and registered nurse. Stress Management: Meditation, gentle yoga-based poses, progressive relaxation, breathing exercises, and meditation (with optional glasses) 1 hour per day, supervised by a certified stress management specialist. Group Support: Participants and their spouses/caregivers participate in a support group one hour/session, 3 days/week, supervised by a licensed mental health professional in a supportive, safe environment.<br>|
| No Intervention: Control (Non-Intervention) Group<br>These patients will be asked to continue their current diet and lifestyle without making any changes for 20 weeks. They will be tested at baseline and after 20 weeks. Then, they will cross over and receive the same lifestyle medicine intervention for 20 weeks and will be tested again after 20 weeks of the intervention and also after 40 weeks of the intervention. After 20 weeks in the randomized control group, patients who no longer meet these eligibility criteria (e.g, a MoCA score <18) will not cross over and will not receive the lifestyle intervention; their data during the first 20 weeks in the control group (when they met the entry criteria) will be used. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Alzheimer Disease Assessment Scale cognitive section (ADAS-Cog) score | The ADAS-Cog test is one of the most frequently used tests to measure cognition in clinical trials. Patients obtain scores of 0 to 70; higher scores indicate poorer performance. | At baseline and also after 20 weeks, 40 weeks. | 
| Change from Baseline in Clinical Global Impression of Change (CGIC) score | The CGIC test is often used in clinical trials of cognition. CGIC scores range from 1 (very much improved) through to 7 (very much worse). | At baseline and also after 20 weeks, 40 weeks. | 
| Change from Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score | The CDR-SOB is a commonly used dementia staging instrument. The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18 (lower is better). | At baseline and also after 20 weeks, 40 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in the microbiome | This test measures the type and relative preponderance of gut organisms at Dr. Rob Knight's lab at UCSD. To assess whether this intervention is associated with a systematic signal in the gut microbiome, he will use 16S rRNA amplicon sequencing, metagenomic sequencing, and untargeted mass spectrometry to analyze stool samples of these study participants. This will provide the relative proportion of organisms in the microbiome of these patients at each time interval. | At baseline and also after 20 weeks, 40 weeks. | 
| Changes from baseline in telomere length | The leukocyte telomere length assay from PBMCs will be performed in the laboratory of Dr. Elizabeth Blackburn at UCSF using the quantitative polymerase chain reaction method to measure telomere length relative to standard reference DNA, expressed as telomere to single-copy gene ratio (T/S). | At baseline and also after 20 weeks, 40 weeks. | 
| Changes from baseline in biomarkers | These are measures of inflammation (C-reactive protein in mg/L), genomics, serum amyloid (C2N), angiogenesis, lipids (total cholesterol, LDL-cholesterol, triglycerides in mg/dl), blood pressure (mm Hg), and weight (pounds). | At baseline and also after 20 weeks, 40 weeks. | 
| Inflammatory biomarkers | Inflammatory Human ProInflammatory 10-Plex: IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-13, TNF-α. Tanzi Lab, Harvard Medical School/Mass General Hospital McCance Center for Brain Health & MassGeneral Institute for Neurodegenerative Disease | At baseline and also after 20 weeks, 40 weeks. | 
| Amyloid peptides | Human Aβ Peptide Panel 1 (6E10) 3-plex: Aβ38, Aβ40, and Aβ42 The Phospho(Thr231)/Total Tau Kit; p-tau 181; p-tau217. Tanzi Lab, Harvard Medical School/Mass General Hospital McCance Center for Brain Health & MassGeneral Institute for Neurodegenerative Disease | At baseline and also after 20 weeks, 40 weeks. | 
| R-PLEX measures | Neurofilament light chain (NF-L): custom-make; R-PLEX Human Neurofilament L Antibody Set; GFAP: custom-make; R-PLEX Human GFAP Antibody Set S100 family proteins: custom-make; R-PLEX Human S100A8/MRP8 Antibody Set. Tanzi Lab, Harvard Medical School/Mass General Hospital McCance Center for Brain Health & MassGeneral Institute for Neurodegenerative Disease | At baseline and also after 20 weeks, 40 weeks. | 
| Angiogenesis biomarkers | Angiogenesis Panel 1 (human) measures 7-plex proteins: VEGF-A, VEGF-C, VEGF-D, Tie-2, Flt-1, PlGF, and FGF (basic). Arnold Lab, Harvard Medical School/Massachusetts General Hospital Alzheimer's Clinical and Translational Research Unit and Interdisciplinary Brain Center. | At baseline and also after 20 weeks, 40 weeks. | 
| Vascular injury panel 2 | Measure 4-plex protein: SAA, CRP, VCAM-1, and ICAM-1. Arnold Lab, Harvard Medical School/Massachusetts General Hospital Alzheimer's Clinical and Translational Research Unit and Interdisciplinary Brain Center. | At baseline and also after 20 weeks, 40 weeks. | 
| Metabolic Panel: 1 Human 7-PLEX | C-Peptide, GIP (active), GLP-1 (active), Glucagon, Insulin, Leptin, PP Quanterix Banyan Panel: p-TAU, NFL, GFAP, UCHL1. Arnold Lab, Harvard Medical School/Massachusetts General Hospital Alzheimer's Clinical and Translational Research Unit and Interdisciplinary Brain Center. | At baseline and also after 20 weeks, 40 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild Cognitive Impairment