Physical Activity, Alzheimer's Disease and Cognition Relative to APOE Genotype (PAAD-2)

The Effect of Physical Activity on Cognition Relative to APOE Genotype (PAAD-2)

Physical activity and Alzheimer's disease (PAAD-2) is a randomized control trial that will assess the effects of exercise on middle-aged (40-65 years) cognitively normal adults who have a heightened risk of Alzheimer's disease (AD) due to family history (FH+). The investigators will also assess the extent to which this effect is moderated by apolipoprotein epsilon-4 (APOE4) carrier status, and will gather critical new experimental evidence on the use of physical activity to improve cognitive performance by persons at the greatest risk of Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Healthy; Physical Activity; Dementia; Alzheimer Disease
• Intervention / Treatment: Behavioral: Physical Activity Condition

Detailed Description

In this study, the investigators follow up on their past research exploring the effects of physical activity on cognitive performance and underlying mechanisms. In particular, the investigators are interested in the potentially different effects that might be realized as a function of a person's genetic risk for Alzheimer's disease. In this study, the investigators extend past work by proposing a randomized clinical trial to: (a) test the causal link between physical activity and cognitive performance in middle-aged adults (40-65 years) with a family history, and (b) determine if the effect is moderated by apolipoprotein epsilon-4 (APOE4) carrier status. The investigators will collect neuroimaging measures of cerebral structure, white matter integrity, and resting state connectivity; assess putative biological markers; and (using moderated mediation analyses) increase understanding of underlying mechanisms and of the extent to which effects are moderated by APOE4 carrier status. To test hypotheses, the investigators will randomly assign 240 cognitively normal, middle-aged adults to a 1-year virtual physical activity program or a usual care control. Those in the intervention will participate in a year-long physical activity program including aerobic exercise performed on your own and resistance exercises led in virtual exercise sessions with an instructor 1 hour/day for 3 days/week for 1 year. Those in the usual care control condition will be asked to maintain their normal lifestyle for one year and then will be given a short-term fitness center membership (contingent upon completion of testing sessions). The investigators will assess cognitive performance at pre-, mid-, and post-test, and obtain MRI scans and blood samples at pre-, mid- and post-test. The investigators will examine the effects of physical activity on cognitive performance and on neurological and biological mechanisms and will explore the moderating role of APOE4.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greensboro, North Carolina, United States, 27402
      • University of North Carolina-Greensboro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Family History of Alzheimer's disease, cognitive impairment
• Able to communicate in English
• Not currently meeting recommendations for physical activity (the recommendations are to exercise 3 days/week for 30+ minutes per day for longer than 3 months)
• Willing to be randomized to either study condition
• Willing to complete all study activities for 1 year

Exclusion Criteria:

• Meet the criteria for clinical cognitive impairment
• Unable to perform physical activity due to known cardiovascular, metabolic, or renal disease and are symptomatic or due to orthopedic limitations
• Self-report history of confounding neurologic, psychiatric, or active severe or functionally disabling neurologic or medical diseases, or any other conditions that might limit exercise or pose a danger to the patient
• Current use of medications to treat symptoms of Alzheimer's disease, that adversely affect cognition, or that impact heart rate
• Meet the criteria for depression using the short form of the Center for Epidemiological Studies Depression Scale
• Traveling for an extended period (>1 month) during the course of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Physical Activity Condition (PAC); Subjects will be asked to attend virtual exercise sessions 3 times a week for 1 year.	Behavioral: Physical Activity Condition; Subjects will attend virtual group exercise sessions 3x/week for 1 year. Each subject will be encouraged to walk at a moderate intensity (target heart rate (HR)= 40-59% HR reserve) dependent on resting HR and age. Subjects will perform aerobic exercise on their own and resistance exercises will be completed in virtual exercise sessions with an instructor 1 hour/day for 3 days/week for 1 year. At the exercise sessions, these participants will be asked to record measures of the exercises completed and may be asked to provide measures of heart rate (assessed by palpation for 20-seconds) and rate of perceived exertion (RPE). They will be asked to submit exercise logs providing this information. Data from exercise logs and exercise specialist records will be reviewed for evidence of progression, consistent attainment of moderate intensity, and with respect to the prescribed duration of the aerobic and strength training components.
No Intervention: Usual Care Control (UCC); Participants in the usual care control will maintain their normal health practices for 1 year. Participants will receive a bi-weekly health newsletter and will be contacted bi-weekly to answer any questions and inquire about the participant's health. Participants self-reported physical activity will be assessed monthly. In this fashion, participants will be contacted by staff every week. Usual care control participants that complete all study related activities including pre-, mid-, and post-test will receive a short-term YMCA membership after post-test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Performance on the Cognitive Domain of Executive Function as Measured With Stroop Interference Reaction Time (RT)	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on Stroop Interference. Stroop interference is calculated using reaction time (RT) data from correct trials and the following formula: Stroop Interference RT = Stroop Incongruent RT - (average (Stroop Congruent RT , Stroop Neutral RT)). Stroop Congruent is also known as Stroop Word, and Stroop Neutral is also known as Stroop Color. RT is recorded in msec and a larger score is indicative of greater interference (worse performance)	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Executive Function as Measured With Trail Making Test Interference	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Comprehensive Trail Making Test (TMT) interference. TMT interference is calculated as total time to complete TMT B (also called Trail 5) minus the total time to complete TMT A (also called Trail 1)which were both recorded in seconds. TMT interference is, therefore, recorded in seconds with a larger score indicative of greater interference (worse performance)	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Executive Function as Measured With NIH Toolbox Dimensional Change Card Sort	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the NIH Toolbox Dimentional Change Card Sort Test (DCCS). We used the recommended outcome of the DCCS computed score. This is calculated automatically within the NIH Toolbox based upon a two-stage process combining a score of 0-5 from the accuracy data with a score of 0-5 from the reaction time data. Thus, scores range from 0-10 with a higher score indicative of better performance.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Executive Function as Measured With the NIH Toolbox Flanker Test.	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the NIH Toolbox Flanker Inhibitory Control and Attention Test. We used the recommended outcome of the Flanker computed score. This is calculated automatically within the NIH Toolbox based upon a two-stage process combining a score of 0-5 from the accuracy data with a score of 0-5 from the reaction time data. Thus, scores range from 0-10 with a higher score indicative of better performance.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Executive Function as Measured With Matrix Reasoning.	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on Matrix Reasoning Accuracy from the Virginia Cognitive Aging Project (VCAP). Version O was given at pre, Version A was given at mid, and Version B was given at post. Possible scores range from 0-1 (i.e., 0% accuracy to 100% accuracy expressed on a 0.00-1.00 scale) with a higher score being indicative of better performance.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Memory as Measured With the Auditory Verbal Learning Test.	Change in memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Auditory Verbal Learning Test. Majdan et al. (1996) Form 1 was given at pre, the standard Rey Auditory Verbal Learning list was given at mid, and Majdan et al. (1996) Form 2 was given at post. These versions are comparable in terms of their scores (Sherman, Tan, & Hrabok, 2022). Possible scores range from 0-15 with a bigger score being indicative of better memory.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Memory as Measured With the Rey-Osterrieth Complex Figure Test	Change in memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Rey Osterreith Complex Figure Test. Tests were scored using the deep learning approach for automated scoring published by Langer et al. eLife 2024;13:RP96017. DOI: https://doi.org/10.7554/eLife.96017. Possible scores range from 0-36 with higher scores being indicative of better memory.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Memory as Measured With the NIH Toolbox Picture Sequence Test	Change in memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the NIH Toolbox Picture Sequence Memory Test - The computed score is an IRT-based theta score of the number of adjacent pairs placed for trial 1 and 2 with a higher score being indicative of better memory. This score is automatically created within the NIH Toolbox. Version A was given at pre, Version B was given at mid, and Version C was given at post. Possible scores range from 200-700 with a higher score being indicative of better performance.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Memory as Measured With the Mnemonic Similarity Test	Change in memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) Lure Discimination Index (LDI) on the Mnemonic Similarity Test (MST). The MST was created based upon the publicly available and validated instructions and stimuli provided by the creators of the task (Stark, Kirwan, & Stark, 2019). Equivalent versions of the test are administered so participants see different stimuli at each testing session and those stimuli were counterbalanced to rotate through the different item types. The formula for calculating the LDI is: p(similar|lure) - p(similar|foil) where p(similar|lure) = Total # of "similar" responses to lure items / 36 and p(similar|foil) = Total # "similar" responses to foil items / 36. Scores range from -1 to +1 with a larger score indicating better discrimination performance.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Attention as Measured With the Paced Auditory Serial Addition Test	Change in attention will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the 2-sec trial of the Paced Auditory Serial Addition Task. Scores are reported as the number of correct responses with possible scores ranging from 0-60 and larger scores being indicative of better attention.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Attention as Measured With the Forward Digit Span Test	Change in attention will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Neurological Assessment Battery (NAB) Digit Span Forward test. Scores are reported as the number of correct trials with possible scores ranging from 0-14 and larger scores being indicative of better attention.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Working Memory as Measured With NIH Toolbox List Sort Working Memory	Change in working memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the NIH Toolbox List Sort Working Memory Test. Scores are reported as the sum of the total number of items correctly recalled and sequenced on Lists 1 and 2 with possible scores ranging from 0-26 and larger scores being indicative of better working memory.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Working Memory as Measured With Spatial Working Memory	Change in working memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) reaction time on the 4-dot trial of the Spatial Working Memory Test. Scores are reported as the average reaction time (RT) for correct responses. Smaller scores are indicative of faster performance (i.e., better performance).	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Working Memory as Measured With Backward Digit Span	Change in working memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) accuracy on the Neurological Assessment Battery (NAB) Digit Span Backwards test. Scores are reported as the number of correct trial with possible scores ranging from 0-14 and larger scores being indicative of better working memory.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Processing Speed as Measured With the Digit Symbol Modalities Test (SDMT)	Change in working memory will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Digit Symbol Modalities Test (SDMT) (Smith, 1973). Scores are reported as the sum of Oral and Written Trial Raw Scores (correct responses) with possible scores ranging from 0-220 and larger scores being indicative of better working memory.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Processing Speed as Measured With the Stroop Word Test	Change in processing speed will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on Stroop Word condition (also known as the Stroop Congruent condition). RT is recorded in msec and a larger score is indicative of slower performance (worse performance)	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Processing Speed as Measured With the Stroop Color Test	Change in processing speed will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on Stroop Color condition (also known as the Stroop Neutral condition). RT is recorded in msec and a larger score is indicative of slower performance (worse performance)	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Performance on the Cognitive Domain of Processing Speed as Measured With the Trail Making Test A	Change in executive function will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) performance on the Comprehensive Trail Making Test (TMT) A (TMT A) (also known as Trail 1). Performance is recorded in seconds with a larger score indicative of slower performance (worse performance)	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Morphology (Whole Brain Volume)	Change in whole brain morphology will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) for total segmented brain volume (i.e., total brain separated from non-brain structures). This is measured as volume (mm3), with volumes ranging from 1,050,000 to 1,350,000, and with higher values being interpreted as better.	Pre-Test and Post-Test (~12 months)
Change in Brain Morphology (Left Hippocampus Volume)	Change in Left Hippocampus Volume will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) for total segmented left hippocampus volume (i.e., left hippocampus segmented away from other regions). This is measured as volume (mm3), ranges from 2500 to 4500, and higher values are better.	Pre-Test and Post-Test (~12 months)
Change in Brain Morphology (Right Hippocampus Volume)	Change in Right Hippocampus Volume will be assessed by comparing Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months) for total segmented right hippocampus volume (i.e., right hippocampus segmented away from other regions). This is measured as volume (mm3), ranges from 2500 to 4500, and higher values are better.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - BDNF	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - Irisin	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - IGF-1	Change in blood biomarkers (BDNF, irisin, IGF-1, glucose, insulin, TNF-⍺, serum amyloid protein (SAP), albumin, ApoE and ⍺-2 macroglobulin) - IGF-1. Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed. The capture antibodies in the kits we received from the company for IGF-1 were not effective. We attempted to secure new kits to conduct the assays, but did not receive the kits in a timely fashion. We intend to conduct these assays upon receipt of the kits and the availability of personnel to perform the assays. The anticipated reporting date for IGF-1 is January 2027.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - Glucose	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - Insulin	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - TNFa	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - SAA	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - ALB	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - ApoE	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Blood Biomarkers (BDNF, Irisin, IGF-1, Glucose, Insulin, TNF-⍺, Serum Amyloid Protein (SAP), Albumin, ApoE and ⍺-2 Macroglobulin) - ⍺-2 Macroglobulin	Blood samples will be taken following a 12-hour fast. Assays will be conducted for brain-derived neurotrophic factor (BDNF), irisin, insulin-like growth factor (IGF)-1, glucose, insulin, tumor necrosis factor (TNF)-⍺, serum amyloid protein (SAP), albumin, apolipoprotein E (ApoE) and ⍺-2 macroglobulin. Change from pre-test to post-test will be assessed.	Pre-Test and Post-Test (~12 months)
Change in Cardiorespiratory Fitness	Fitness will be assessed by comparing predicted VO2max at Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months). Fitness will be assessed using a submaximal graded aerobic exercise test performed on a treadmill. Oxygen uptake (VO2) at each stage is estimated based on the treadmill speed and grade during a ramped exercise protocol performed until volitional exhaustion or test termination due to symptom limitations. The VO2max estimation uses the slope of the regression line between the heart rates (HR) of the last two stages to extrapolate to the participant's predicted VO2 at their age-predicted max HR (220-age). If HR at either of the last two stages is <110, VO2 could not be reliably calculated, and we consider the participant to have insufficient data (ID). We have explored other options for estimating VO2 max, but believe this is the best option available.	Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Right Lateral Parietal, Posterior Cingulate Cortex	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Left Lateral Parietal, Right Lateral Parietal	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Left Lateral Parietal, Posterior Cingulate Cortex	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Medial Prefrontal Cortex, Posterior Cingulate Cortex	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Medial Prefrontal Cortex, Right Lateral Parietal	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)
Change in Brain Activity (Resting-state Connectivity) Medial Prefrontal Cortex, Left Lateral Parietal	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pre-Test and Post-Test (~12 months)

Collaborators and Investigators

• Sponsor: University of North Carolina, Greensboro
• Collaborators: National Institute on Aging (NIA); Wake Forest University Health Sciences
• Investigators: Principal Investigator: Jennifer Etnier, PhD, UNC Greensboro

Publications and helpful links

General Publications

• Park KS, Etnier JL. An innovative protocol for the artificial speech-directed, contactless administration of laboratory-based comprehensive cognitive assessments: PAAD-2 trial management during the COVID-19 pandemic. Contemp Clin Trials. 2021 Aug;107:106500. doi: 10.1016/j.cct.2021.106500. Epub 2021 Jul 2.
• Park KS, Ganesh AB, Berry NT, Mobley YP, Karper WB, Labban JD, Wahlheim CN, Williams TM, Wideman L, Etnier JL. The effect of physical activity on cognition relative to APOE genotype (PAAD-2): study protocol for a phase II randomized control trial. BMC Neurol. 2020 Jun 6;20(1):231. doi: 10.1186/s12883-020-01732-1.

Helpful Links

• UNCG PAAD2

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Actual): December 21, 2024
• Study Completion (Actual): December 21, 2024

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: exercise; dementia; Alzheimer; Alzheimer's; Alzheimers
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Behavior; Alzheimer Disease; Dementia; Motor Activity
• Other Study ID Numbers: 18-0228; R01AG058919 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data documentation and de-identified data will be deposited for sharing consistent with applicable laws and regulations. Data will be available in a de-identified anonymous state and in a .csv format. Data will be shared by exporting the data from RedCap into a .csv file archived under the study principal investigator's institutional profile with University of North Carolina Greensboro (UNCG) University Libraries institutional repository North Carolina Digital Online Collection of Knowledge and Scholarship (NC DOCKS).

The data will also be shared through the Global Alzheimer's Association Interactive Network (GAAIN), a federated data system designed to foster data sharing and the development of collaborations for researchers interested in Alzheimer's related data. Interested scientists can explore meta data from PAAD-2 and from other studies. By becoming a partner, a description of PAAD-2 and link to contact the principal investigator will be made available at www.gaain.org.

• IPD Sharing Time Frame: Consistent with the recommendations from the Collaboration for Alzheimer's Prevention (CAP), pre-randomization data will be deposited within 12 months of enrollment completion. Consistent with the National Institutes of Health (NIH) guidelines, post-randomization data will be embargoed until publication of the main findings of the study (i.e. those findings relevant to the specific aims) or two years following study closure (whichever comes earlier). Requests for data sharing that come before the end of the embargo period will be considered on a case-by-case basis by the principal investigator.
• IPD Sharing Access Criteria: Investigators interested in having access to the data will submit their request through GAAIN and then will be asked to submit a proposal to the principal investigator. The proposal should include institutional affiliation, a current resume or vita, source of funding (if applicable), and a detailed explanation of the research question and the data required. All applicants will also be required to sign an agreement of confidentiality. This agreement prohibits the use of the data in any way that would allow for the identification of individual participants.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No