Cognition and Neuroplasticity Sedentary Adults After 8 Weeks of Aerobic Exercise

Assessing Cognitive Improvements, Brain Neuroplasticity and the Role of Genetic Factors After Aerobic Exercise in Sedentary Adults

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03804528

Enrollment

Registered

2019-01-15

Start date

2019-03-08

Completion date

2021-05-28

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sedentary Behavior

Brief summary

Detailed description

The overall goal of the proposed study is to evaluate the effects of an 8-week aerobic exercise program on cognition and determine the relationship between cognitive improvements and neuroplasticity. The primary study aims include: 1) Quantify improvements in cognitive performance after 8 weeks (150 min per week) of moderate intensity aerobic exercise in sedentary adults ≥ 55 years of age; 2) Determine an association between changes in plasticity, aerobic capacity, and cognitive performance overall and by cognitive domain, after 8 weeks of moderate intensity aerobic exercise in sedentary adults ≥ 55 years of age. Due to challenges posed by the COVID-19 pandemic, social distancing practices, and aiming to create a feasible scenario to continue the current study, we propose an additional option to safely adapt study methods to deliver the study in a home-based, fully remote manner. Importantly, this scenario also presents as an opportunity to collect meaningful data on our specific aims while translating this successful research program into a remote/home-based mode of delivery. A remote/home based option may also yield valuable preliminary data that will be relevant for planning future exercise studies in aging adults in the present new normal. Therefore, this research project consist of two equivalent options: Option A: Current, IRB-approved, in-person methods pending appropriateness based on current University of Miami recommendations and standard operating procedures as it relates to the COVID-19 pandemic. Option B: Remote option of current methods to maximize recruitment. This will be the only option until the study team obtains approval to resume Option A (as per University's safety guidelines).

Interventions

BEHAVIORALAerobic Exercise

Participants will be fitted with a heart rate monitor and will be instructed to walk (or trot) to maintain 55-64% of maximal heart rate (determined by exercise test) for the first 4-weeks of exercise or to maintain 65-90% of maximal heart rate (determined by exercise test) for the second 4-weeks of exercise during each session. Participants are provided the option to participate remotely due to COVID-19 pandemic, as detailed below. Both options are designed to be equivalent in intervention and outcome measures. Option A: Current, IRB-approved, in-person methods pending appropriateness based on current University of Miami recommendations and standard operating procedures as it relates to the COVID-19 pandemic. Option B: Remote option of current methods to maximize recruitment. This will be the only option until the study team obtains approval to resume Option A (as per University's safety guidelines).

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

55 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* age ≥ 55years * no clinically detectable cognitive impairment (MoCA score ≥ 24 and Clinical Dementia Rating (CDR) score of 0) * low activity level (individuals who do not engage in regular exercise, or currently exercise once a week or less) * primary language is English

Exclusion criteria

* any unstable medical condition (i.e.: uncontrolled hypertension or uncontrolled diabetes) * medical contraindication to physical exercise * contraindication to TMS Neuroplasticity testing, as per the TMS Safety Guidelines. * History of fainting spells of unknown or undetermined etiology that might constitute seizures * History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG or family history of treatment resistant epilepsy * Any current history of a psychiatric illness * No medication is an absolute exclusion from TMS. Medications will be reviewed by the Principal Investigator and a decision about inclusion will be made based on the following: * The subject's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other Central Nervous System (CNS) active drugs. * The published TMS guidelines review medications to be considered with TMS. * Any metal in the brain, skull or elsewhere unless approved by the responsible MD * Any medical devices (i.e. Cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) * Intracranial lesion * Substance abuse or dependence within the past six months * Pregnant women * Vulnerable populations such as prisoner's * People unable to consent themselves * Subjects who, in the Investigator's opinion might not be suitable for the study

Design outcomes

Primary

Measure	Time frame	Description
Cognitive Performance (Digital Span)	Baseline and Post-intervention (after 8 weeks of exercise)	Digital span - Subtest of the Wechsler Adult Intelligence Scale fourth edition; Three sections: Digits Forward, Digits Backward, and Digits Sequencing. For each section, min. raw score value: 0; max. raw score value: 16. Higher the score, better the outcome.
Change in TMS Plasticity Measures	Baseline and Post-intervention (after 8 weeks of exercise)	Index of the duration of the Theta-burst stimulation (TBS)-induced modulation of corticospinal excitability. This outcome measure refers to the identification of the time point (T5, T10, T15, T20 and T30). at which the normalized motor evoked potential (MEP) amplitude returns to baseline values (T0 or Baseline). This measure will be in Minutes Post Theta-Burst stimulation. This is a neurophysiological measure, and no group-based norms apply.
Cognitive Performance (RBANS)	Baseline and Post-intervention (after 8 weeks of exercise)	Cognitive performance will be assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) a neuropsychological test battery in executive function, processing speed, learning, and language. It is made up of a series of twelve subtests that take approximately 30 minutes. For each of these, a lower number correct is indicative of a higher cognitive deficit. Subtests are their scales are: RBANS Semantic Fluency (0-unlimited), RBANS Picture Naming (0-10), RBANS List Learning (0-40), RBANS List Recall (0-10), RBANS Story Memory (0-24), RBANS Story Recall (0-12), RBANS List Recognition (0-20), RBANS Digit Span (0-16), RBANS Figure Recall (0-20), RBANS Coding (0-89), RBANS Figure Copy (0-20), RBANS Line Orientation (0-20).
Cognitive Performance (DKEFS)	Baseline and Post-intervention (after 8 weeks of exercise)	Cognitive performance will be assessed using a neuropsychological test battery in executive function, processing speed, learning, and language. The D-KEFS Verbal Fluency Test measures the ability to generate words fluently in an effortful phonemic format (letter fluency),from overlearned concepts (category fluency), and simultaneously shifting between overlearned concepts (category switching). Raw scores (correct responses, correct number of switches between categories) are converted to scaled scores with a mean of 10 and a standard deviation of 3. Higher scores reflect higher verbal fluency, and an increase in score pre-post would indicate improvement.

Secondary

Measure	Time frame	Description
Change in Cardiorespiratory Fitness	Baseline and Post-intervention (after 8 weeks of exercise)	Heart rate recovery (HRR) is the primary measure for cardiorespiratory fitness. HRR is defined as the change in the heart rate from the peak of exercise to the heart rate after 1-min (HRR-1) and 2-min test cessation (HRR-2).
Circulating Markers of Endothelium Function (BDNF)	Baseline	Blood samples will be collected to measure: brain-derived neurotrophic factor (BDNF) levels (measured as pg/mL).
Circulating Markers of Endothelium Function (VEGF)	Baseline	Blood samples will be collected to measure vascular endothelial growth factor (VEGF) (measured as pg/mL).
Circulating Markers of Endothelium Function (Hs-CRP)	Baseline	Blood samples will be collected to measure high sensitivity C reactive protein (HS-CRP) (measured as mg/L).

Countries

United States

Participant flow

Participants by arm

Arm	Count
Exercise Group (All Participants) Each participant will engage in 60 minute in-person daily sessions delivered 3 times/week for 8 consecutive weeks (a total of 24 sessions). Aerobic Exercise in person: Participants will be fitted with a heart rate monitor and will be instructed to walk (or trot) to maintain 55-64% of maximal heart rate (determined by exercise test) for the first 4-weeks of exercise or to maintain 65-90% of maximal heart rate (determined by exercise test) for the second 4-weeks of exercise during each session. Two equivalent options provided for participation, to accommodate for COVID-19 pandemic guidelines. Option A: Current, IRB-approved, in-person methods pending appropriateness based on current University of Miami recommendations and standard operating procedures as it relates to the COVID-19 pandemic. Option B: Remote option of current methods to maximize recruitment. This will be the only option until the study team obtains approval to resume Option A (as per University's safety guidelines).	52
Total	52

Arm

Count

Exercise Group (All Participants)

Each participant will engage in 60 minute in-person daily sessions delivered 3 times/week for 8 consecutive weeks (a total of 24 sessions). Aerobic Exercise in person: Participants will be fitted with a heart rate monitor and will be instructed to walk (or trot) to maintain 55-64% of maximal heart rate (determined by exercise test) for the first 4-weeks of exercise or to maintain 65-90% of maximal heart rate (determined by exercise test) for the second 4-weeks of exercise during each session. Two equivalent options provided for participation, to accommodate for COVID-19 pandemic guidelines. Option A: Current, IRB-approved, in-person methods pending appropriateness based on current University of Miami recommendations and standard operating procedures as it relates to the COVID-19 pandemic. Option B: Remote option of current methods to maximize recruitment. This will be the only option until the study team obtains approval to resume Option A (as per University's safety guidelines).

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Health Reasons	5
Overall Study	Time Commitment	18

Baseline characteristics

Characteristic	Exercise Group (All Participants)
Age, Continuous	62.9 years STANDARD_DEVIATION 6.8
BMI Normal (18.5-24.9)	14 Participants
BMI Obese Class 2 (35-39.9)	6 Participants
BMI Obese Class I (30-34.9)	13 Participants
BMI Overweight (25-29.9)	19 Participants
Education Level Graduate Degree	16 Participants
Education Level High School	9 Participants
Education Level Undergraduate/Associate Degree	27 Participants
Health Status Alcohol Consumption	41 Participants
Health Status Arthritis or joint pain	22 Participants
Health Status Caffeine consumption	49 Participants
Health Status Depression/anxiety	13 Participants
Health Status Diabetes	4 Participants
Health Status Fainting/Dizzy spells	6 Participants
Health Status Hearing loss	6 Participants
Health Status Heart disease	8 Participants
Health Status Hospitalized	41 Participants
Health Status Hypertension	25 Participants
Health Status Lung/Asthma disease	11 Participants
Health Status Migraine/Severe headache	9 Participants
Health Status Smoking History	13 Participants
Health Status Stomach/Intestinal disease	4 Participants
Health Status Taking prescribed medication	41 Participants
Health Status Thyroid disease	12 Participants
Health Status Tumor or cancer	10 Participants
Health Status Under beta-blocker	6 Participants
MoCA - Montreal Cognitive Assessment Global Cognition	26.4 units on a scale STANDARD_DEVIATION 1.9
Race/Ethnicity, Customized Asian	1 Participants
Race/Ethnicity, Customized Black	7 Participants
Race/Ethnicity, Customized Hispanic	17 Participants
Race/Ethnicity, Customized Hispanic/White	3 Participants
Race/Ethnicity, Customized White	24 Participants
Sex: Female, Male Female	40 Participants
Sex: Female, Male Male	12 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 52
other Total, other adverse events	0 / 52
serious Total, serious adverse events	0 / 52

Outcome results

Primary

Change in TMS Plasticity Measures

Index of the duration of the Theta-burst stimulation (TBS)-induced modulation of corticospinal excitability. This outcome measure refers to the identification of the time point (T5, T10, T15, T20 and T30). at which the normalized motor evoked potential (MEP) amplitude returns to baseline values (T0 or Baseline). This measure will be in Minutes Post Theta-Burst stimulation. This is a neurophysiological measure, and no group-based norms apply.