Physical Activity, Alzheimer's Disease and Cognition Relative to APOE Genotype

NCT03876314 | Completed

• 2 other identifiers: 18-0228R01AG058919
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Dementia; Alzheimer Disease; Physical Activity

Keywords

Alzheimer's; Alzheimers; Alzheimer; dementia; exercise

Outcome Measures

Primary Outcomes (18)

• Change in performance on the cognitive domain of executive function as measured with Stroop Interference

  Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Stroop Interference.

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on Trail Making Test interference.

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of executive function as measured with Dimensional Change Card Sort

  Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Dimensional Change Card Sort

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of executive function as measured with the Flanker test.

  Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on the Flanker test.

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on Matrix Reasoning.

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Auditory Verbal Learning Test.

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Rey-Osterrieth Complex Figure Test

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of memory as measured with the Picture Sequence test

  Change in memory will be assessed by comparing post-, mid-, and pre-test performance on the Picture Sequence test.

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Mnemonic Similarity Test

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Paced Auditory Serial Addition Test

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Forward Digit Span

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of working memory as measured with List Sort Working Memory

  Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the List Sort Working Memory

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Spatial Working Memory

  Pretest, 6 months, and 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 post-, mid-, and pre-test performance on the Backward Digit Span

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of processing speed as measured with the Wechsler Adult Intelligence Scale (WAIS-IV) Digit Symbol Task

  Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Wechsler Adult Intelligence Scale (WAIS-IV) Digit Symbol Task

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of processing speed as measured with the Stroop Color Test

  Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Stroop Color Test

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of processing speed as measured with the Stroop Word Test

  Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Stroop Word Test

  Pretest, 6 months, and 12 months

• Change in performance on the cognitive domain of processing speed as measured with the Trail Making Test A

  Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Trail Making Test A

  Pretest, 6 months, and 12 months

Secondary Outcomes (4)

• Change in brain morphology (whole brain and hippocampal volumes)

  Pretest and 12 months

• Change in brain activity (resting-state connectivity)

  Pretest and 12 months

• Change in blood biomarkers (BDNF, irisin, IGF-1, glucose, insulin, TNF-⍺, serum amyloid protein (SAP), albumin, ApoE and ⍺-2 macroglobulin)

  Pretest and 12 months

• Change in cardiorespiratory fitness

  Pretest, 6 months, and 12 months

Study Arms (2)

Physical Activity Condition (PAC)

EXPERIMENTAL

Subjects will be asked to attend virtual exercise sessions 3 times a week for 1 year.

Behavioral: Physical Activity Condition

Usual Care Control (UCC)

NO INTERVENTION

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.

Interventions

Physical Activity Condition BEHAVIORAL

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.

Physical Activity Condition (PAC)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Greensboro: lead
• Wake Forest University Health Sciences: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of North Carolina-Greensboro

Greensboro, North Carolina, 27402, United States

Location

Related Publications (2)

• 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.

  PMID: 34217888 DERIVED

• 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.

  PMID: 32503473 DERIVED

MeSH Terms

Conditions

Dementia; Alzheimer Disease; Motor Activity

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Behavior

Study Officials

• Jennifer Etnier, PhD

  UNC Greensboro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The outcomes assessor will be masked to intervention assignment and APOE4 carrier status. The interventionist will be masked to APOE4 carrier status.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: March 15, 2019
• Study Start: May 23, 2019
• Primary Completion: December 21, 2024
• Study Completion: December 21, 2024
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• 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.
• 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.

Locations

US (1)