Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial: LEARNit Study

The purpose of this study is to examine the effects of modifiable lifestyle factors including exercise and healthy living on brain health. The investigators will compare 2 types of interventions, moderate aerobic walking vs. healthy living education, over 6 months to evaluate changes in brain health, cognition, and physical function in older adults with cognitive concerns.

Study Overview

• Status: Completed
• Conditions: Aging; Cognitive Ability, General
• Intervention / Treatment: Behavioral: Moderate-aerobic walking; Radiation: Positron Emission Tomography (PET) scan; Device: Physical activity monitor; Behavioral: Healthy living education

Detailed Description

Cognitive decline in older adults is a major public health issue. The cost of caring for older adults with substantial cognitive impairment, like those with Alzheimer's Disease in the US is approximately $200 billion a year, causing major societal, economic, and caregiving burden. Despite great advances towards diagnosing these problems, the discovery of effective treatments has been minimal. Exploring non-pharmacological interventions, such as exercise and healthy living, have gained momentum. These promising, modifiable lifestyle interventions have the potential for delaying disease onset and slowing decline in cognition. However, the therapeutic effect of lifestyle interventions in patients with mild cognitive impairment, a prime intervention period for treatment, is not well understood. Therefore, in this study, the investigators will examine brain, body, and cognitive changes in older adults who engage in moderate-aerobic walking or healthy living education.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90032
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female
2. English-speaking
3. 55-80 years old
4. Exhibits sedentary behavior
5. Objective cognitive impairment
6. Mini-Mental State Exam score > 26
7. Perform at least 1 standard deviations below normative values on cognitive tests
8. Absence of dementia
9. Ability to complete both MRI and PET scans
10. Physically capable of completing health programs

Exclusion Criteria:

1. Baseline dementia
2. History of a neurological disorder
3. Current psychiatric illness
4. Head trauma with a loss of consciousness > 10 minutes
5. Severe sensory deficits
6. Substance abuse
7. Depression (GDS < 8 of 15)
8. Inability to perform intervention (e.g., inability to walk without assistance)
9. Contraindications to MRI scan (e.g., pacemaker)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate-aerobic walking; Participants will complete a 6-month home-based moderate-aerobic walking program of 150 minutes per week with the assistance of an interventionist.	Behavioral: Moderate-aerobic walking; Radiation: Positron Emission Tomography (PET) scan; Radioligand that binds to proteins using a PET/CT scanner.; Device: Physical activity monitor; Wrist device that will track daily physical activity
Placebo Comparator: Healthy Living Education; Participants will receive monthly topics on healthy living lifestyles for self-paced reading over 6 months with the assistance of an interventionist.	Radiation: Positron Emission Tomography (PET) scan; Radioligand that binds to proteins using a PET/CT scanner.; Device: Physical activity monitor; Wrist device that will track daily physical activity; Behavioral: Healthy living education

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Magnetic Resonance Imaging (fMRI) Brain Scan as a Measure of Brain Function	Functional MRI has proven to be an effective non-invasive, in-vivo tool for measuring brain function via the BOLD signal. Growing evidence supports that fMRI BOLD can detect neuronal changes that occur very early in the disease process. The hippocampus has been shown to be a selectively vulnerable region in AD, and several studies, including our own, identified a aberrant brain signal in the hippocampus in older adults. The typical range for this outcome is -10 to 10 with higher scores indicating better brain function.	Baseline and Follow-up at 6 months
Mnemonic Similarity Test as a Measure of Memory (Cognition)	The participants will encode a series of objects presented on a computer. Following the encoding period, they will begin their fMRI scan and be asked to indicate if they recognize the objects on the screen, which include targets (previously seen objects), lures (objects that are similar to previously seen objects) and novel (unrelated objects). The discrimination between Targets and Lures will indicate the rate at which participants "correctly reject" the Lures (via pattern separation) or "false alarm" to the Lures (via pattern completion). The theoretical range for this outcome is -1 to 1 with higher scores indicating better memory function.	Baseline and Follow-up at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amyloid Positron Emission Tomography (PET) Scan as a Measure of Tracer Binding (SUVr)	Each participant received PET scans with Neuraceq [florbetaben F 18 (FBB)] to measure amyloid-beta PET binding. IV injections of the tracers (FBB, -8.11 6 0.6 mCi) were done outside of the scanning room. Four 5-min frames were acquired 90 minutes after injection.	Baseline and Follow-up at 6 months
Single-stage Treadmill Test	This is a measure of cardiovascular fitness. This test has been validated against peak VO2 max with r=0.96. Heart rate response is monitored with a Polar heart rate monitor and the heart rate at the end of the 4 min test is used to estimate VO2max using an established equation for conversion. The theoretical range for this outcome is 0 to 200 with higher scores indicating better cardiovascular fitness.	Baseline and Follow-up at 6 months
Modified Physical Function Test	This test is a measure of multiple domains related to functional activities of daily living. Each physical activity in score is of varying difficulty level. The theoretical range for this outcome is 0 to 36 with higher scores indicating better physical function.	Baseline and Follow-up at 6 months
Brain-derived Neurotropic Factor (BDNF) as a Measure From Blood	We will quantitatively analyze pre- and post-measurements of brain derived neurotrophic factor (BDNF). BDNF has been shown to increase after exercise intervention in humans and peripheral increases in these hormones correlate to cell proliferation in the dentate gyrus of the hippocampus. We measure total BDNF from plasma.	Baseline and Follow-up at 6 months

Collaborators and Investigators

• Sponsor: University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2016
• Primary Completion (Actual): July 13, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: March 28, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimated): April 4, 2016

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Mild Cognitive Impairment; Brain Imaging
• Other Study ID Numbers: AG046928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data requests will be reviewed by the data committee. Approved investigators will be provided de-identified participant-level data from the trial as a .CSV file.
• IPD Sharing Time Frame: Data will be available starting July 1, 2025 and for at least 3 years.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP