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Can Lifestyle Changes Reverse Early-Stage Alzheimer's Disease

Not Applicable
Conditions
Alzheimer Disease
Interventions
Behavioral: Lifestyle medicine
Registration Number
NCT04606420
Lead Sponsor
Preventive Medicine Research Institute
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
51
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Experimental (Intervention) GroupLifestyle medicineThese 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.
Primary Outcome Measures
NameTimeMethod
Change from Baseline in Alzheimer Disease Assessment Scale cognitive section (ADAS-Cog) scoreAt baseline and also after 20 weeks, 40 weeks.

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.

Change from Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) scoreAt baseline and also after 20 weeks, 40 weeks.

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).

Change from Baseline in Clinical Global Impression of Change (CGIC) scoreAt baseline and also after 20 weeks, 40 weeks.

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).

Secondary Outcome Measures
NameTimeMethod
Vascular injury panel 2At baseline and also after 20 weeks, 40 weeks.

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.

Changes from baseline in the microbiomeAt baseline and also after 20 weeks, 40 weeks.

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.

Changes from baseline in telomere lengthAt baseline and also after 20 weeks, 40 weeks.

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).

Amyloid peptidesAt baseline and also after 20 weeks, 40 weeks.

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

Metabolic Panel: 1 Human 7-PLEXAt baseline and also after 20 weeks, 40 weeks.

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.

Changes from baseline in biomarkersAt baseline and also after 20 weeks, 40 weeks.

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).

Inflammatory biomarkersAt baseline and also after 20 weeks, 40 weeks.

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

R-PLEX measuresAt baseline and also after 20 weeks, 40 weeks.

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

Angiogenesis biomarkersAt baseline and also after 20 weeks, 40 weeks.

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.

Trial Locations

Locations (4)

McCance Center for Brain Health, Harvard Medical School/Mass General Hospital

🇺🇸

Boston, Massachusetts, United States

Preventive Medicine Research Institute

🇺🇸

Sausalito, California, United States

Renown Health Institute of Neurosciences

🇺🇸

Reno, Nevada, United States

University of California, San Diego

🇺🇸

San Diego, California, United States

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