Clinical trial NCT03876314: Physical Activity, Alzheimer's Disease and Cognition Relative to APOE Genotype
Official title: The Effect of Physical Activity on Cognition Relative to APOE Genotype (PAAD-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Dementia
Alzheimer Disease
Physical Activity
Keywords: Alzheimer's
Alzheimers
Alzheimer
dementia
exercise
Lead sponsor: University of North Carolina, Greensboro
Sponsor class: OTHER
Collaborators: name: Wake Forest University Health Sciences
name: National Institute on Aging (NIA)
First posted: 2019-03-15
Enrollment: 180
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in performance on the cognitive domain of executive function as measured with Stroop Interference
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of executive function as measured with Trail Making Test Interference
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of executive function as measured with Dimensional Change Card Sort
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of executive function as measured with the Flanker test.
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of executive function as measured with Matrix Reasoning.
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of memory as measured with the Auditory Verbal Learning Test.
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of memory as measured with the Rey-Osterrieth Complex Figure Test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of memory as measured with the Picture Sequence test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of memory as measured with the Mnemonic Similarity Test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of attention as measured with the Paced Auditory Serial Addition Test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of attention as measured with the Forward Digit Span test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of working memory as measured with List Sort Working Memory
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of working memory as measured with Spatial Working Memory
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of working memory as measured with Backward Digit Span
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of processing speed as measured with the Wechsler Adult Intelligence Scale (WAIS-IV) Digit Symbol Task
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of processing speed as measured with the Stroop Color Test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of processing speed as measured with the Stroop Word Test
timeFrame: Pretest, 6 months, and 12 months
measure: Change in performance on the cognitive domain of processing speed as measured with the Trail Making Test A
timeFrame: Pretest, 6 months, and 12 months
Secondary outcomes:
measure: Change in brain morphology (whole brain and hippocampal volumes)
timeFrame: Pretest and 12 months
measure: Change in brain activity (resting-state connectivity)
timeFrame: Pretest and 12 months
measure: Change in blood biomarkers (BDNF, irisin, IGF-1, glucose, insulin, TNF-⍺, serum amyloid protein (SAP), albumin, ApoE and ⍺-2 macroglobulin)
timeFrame: Pretest and 12 months
measure: Change in cardiorespiratory fitness
timeFrame: Pretest, 6 months, and 12 months
Other outcomes:
Locations:
city: Greensboro
country: United States
facility: University of North Carolina-Greensboro
state: North Carolina
Study officials:
affiliation: UNC Greensboro
name: Jennifer Etnier, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.