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

Healthy Clinical Trial

— PAAD-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03876314
• Other study ID #: 18-0228
• Secondary ID: R01AG058919
• Status: Recruiting
• Phase: N/A
• Start date: May 23, 2019
• Est. completion date: December 2023

Study information

• Verified date: May 2023
• Source: University of North Carolina, Greensboro
• Contact: Jennifer Etnier, PhD
• Phone: (336) 334-3037
• Email: jletnier[@]uncg.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia
• Healthy
• Physical Activity

Intervention

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.

Locations

Country	Name	City	State
United States	University of North Carolina-Greensboro	Greensboro	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Greensboro	National Institute on Aging (NIA), Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change in brain morphology (whole brain and hippocampal volumes)	MRI will be used to measure brain morphology including whole brain and hippocampal volumes and change will be assessed from pre-test to post-test.	Pretest and 12 months
Secondary	Change in brain activity (resting-state connectivity)	Functional MRI will be used to measure brain activity including resting-state connectivity and change will be assessed from pre-test to post-test.	Pretest and 12 months
Secondary	Change in blood biomarkers (BDNF, irisin, IGF-1, glucose, insulin, TNF-?, serum amyloid protein (SAP), albumin, ApoE and ?-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.	Pretest and 12 months
Secondary	Change in cardiorespiratory fitness	Fitness will be assessed using a submaximal graded aerobic exercise test performed on a treadmill. Oxygen uptake (VO2) will be measured during a ramped exercise protocol performed until volitional exhaustion or test termination due to symptom limitations. Change across time will be assessed.	Pretest, 6 months, and 12 months

External Links

•   UNCG PAAD2