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

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. MRI data was not available for one participant in the Healthy Living Education group, resulting in an N of 29 for all fMRI measures.

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization.

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization.

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization. BDNF Plasma sample for one participant in the Healthy Living Education group did not pass QC thresholds and was excluded from analyses.

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization.

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.

Time frame: Baseline and Follow-up at 6 months

Population: Definition of ITT analysis sample: all eligible participants who (1) began the intervention and (2) completed baseline assessment and 6-month assessment for the primary analysis of fMRI BOLD and MST behavioral test. All consented, randomized participants are grouped according to the treatment assigned at randomization.