Resistance Training and Neuroimaging — RTNI  

Cognitive Decline Clinical Trial

Official title: Cerebrovascular Mechanisms of Cognitive Enhancement After Periodized Resistance Training in Older Adults

Status Completed

Clinical Trial Summary

Aging tends to compromise the ability to solve problems, remember details, and process information. At the extreme level, this normal cognitive decline can interfere with independent living. Because most brain dysfunctions become irreversible before patients show clear signs in the clinic, there is a pressing need to prioritize preventative countermeasures. Exercise is a promising strategy to slow or reverse these losses. While most studies have looked at running or cycling exercise, little is known about the effects of weight lifting exercise. In addition, vascular health is intimately linked with cognitive abilities and risk of stroke, making it a primary target for intervention. Previous weight lifting studies suggest that blood vessels in the brain are a likely site of adaptation.

The goal of this research is to understand how weight lifting exercise improves cognitive function in older adults. Specifically, the contribution of blood vessel changes in the brain after 12 weeks of weight lifting exercise 3 days per week. These vascular improvements may provide the link between physical and cognitive health, while simultaneously reducing the risk of cardiovascular disease and stroke. To determine this, advanced brain imaging techniques will be used to measure blood flow/volume changes in the brain non-invasively. Physical capacity (i.e. strength), body composition (i.e. lean mass, fat mass), and blood markers will also be assessed using standard protocols, and each of these variables will be tested for their relationship with cognitive functions.

Understanding how weight lifting exercise improves cognitive function will support the development of comprehensive treatments targeting overall brain health. With no current cures for dementia, this information will be vital in prescribing exercise for specific patient needs to reducing the risk of dementia and stroke. In addition, the promise of exercise therapies extends beyond the target disease, having further benefits to the well-being of participants. These types of treatments positively impact fundamental aging processes, and thus reduce the risk of all-cause mortality. Even with moderate benefits to a specific disease like dementia, the global impact on healthcare would be substantial.

Clinical Trial Description

Exercise is a promising strategy to slow or prevent the progression of cognitive decline and dementia. While resistance training (RT) is a popular form of exercise recommended for older adults for its putative role in the protection against sarcopenia, its effects on brain health have been less-well studied. Previous RT studies involving traditional protocols highlight robust and lasting benefits to fluid cognition. In contrast, little is known about the effects of high-intensity RT with advanced periodization techniques. Such protocols may produce similar improvements in shorter durations, thus improving clinical utility. In addition, the mechanisms of RT-induced cognitive enhancement are not well understood. Defining the dominant neural and physiological processes that underlie these protective effects is essential to explain the variance in cognitive responses and to design optimal treatment strategies for the aging population.

The effectiveness of RT interventions for cognitive health likely depends on maximizing gains in muscular strength. Therefore, the investigators will apply strength and conditioning principles and advanced neuroimaging techniques to a 12-week periodized RT intervention to determine neuroprotective contributions. Cerebrovascular (CV) function is a major component of brain health and a primary mechanism of cognitive enhancement after aerobic training. However, the potential for RT to influence these pathways has not been determined. This study will test and extend previous cross-sectional evidence linking RT with CV function. In addition, RT interventions have been demonstrated to improve systemic vascular function and cognition independently. Thus, the investigators hypothesize that RT improves cognitive function through muscular strength and CV adaptations. The overall goal of this proposal is to investigate changes in cognition and CV function in 23 healthy older adults 60-80 years of age, serving as their own controls, and explore the mechanisms that mediate these effects. To address this goal, the investigators propose the following aims:

Aim 1: To determine whether 12 weeks of periodized RT improves fluid cognition in older adults. The NIH Toolbox® Cognition Battery will be administered to assess changes in executive function, attention, episodic memory, processing speed, working memory, and language. Composite scores will be computed for fluid, crystallized, and global cognitive function.

Hypothesis: A 12-week periodized RT program designed specifically to maximize strength gains improves fluid cognition in healthy older adults.

Aim 2: To evaluate the effects of periodized RT on CV function in older adults. Arterial spin labeling (ASL) MRI techniques will be used to assess changes in CV function by quantifying the effects on resting cerebral blood flow, intracranial vascular compliance, and arterial transit time. Mediation analyses will be performed to determine the mediating effects of CV function on cognition.

Hypothesis: High-intensity RT can improve CV function in healthy older adults.

Aim 3: To explore associations between brain adaptations and potential mechanisms of benefit, including: 1) physical capacity (e.g. muscular strength), body composition, and functional mobility; 2) putative blood markers of exercise-induced brain plasticity; 3) cardiovascular risk factors; and 4) brain morphometry and resting state brain activity. Significant changes will be analyzed for mediation of cognitive function to identify the major pathways that underlie the protective effects of RT.

For the practicality of this study, participants will serve as their own controls. All control periods will take place before the RT intervention to ensure that results are not confounded by detraining effects or long-term cognitive benefits of RT. All participants will undergo testing at baseline, pre-intervention, and post-intervention. The NIH Toolbox Cognition Battery will provide a standard set of comprehensive assessment tools. Three test versions will be used to reduce practice effects. During MRI scans, ASL techniques will be used to assess CV function and standard sequences will be used for structural MRI (e.g. T2-weighted FLAIR and T1-weighted MP-RAGE), resting state function MRI (rfMRI), and diffusion tensor imaging (DTI). Physical outcomes will be assessed using standard testing procedures in exercise physiology research, including blood pressure, body composition, physical function, muscle strength and estimated VO2max. Validated questionnaires for quality-of-life, physical activity, sleep quality, and interpersonal support will be administered.

Participants will perform a periodized and progressive total-body resistance training program emphasizing development of lower and upper body strength. All 36 training sessions (3 days per week for 12 weeks) will be performed at the CERC, supervised by an exercise specialist. Mesocycle I (weeks 1-4) will emphasize muscular hypertrophy to develop a muscular and metabolic base for more intense training in later phases. Training bouts will consist of 4-6 resistance exercises with 2-4 sets per exercise and 8-10 repetitions per set. Mesocycles II (weeks 5-8) and III (weeks 9-12) will emphasize strength development. Training bouts will consist of 4-6 resistance exercises with 3-5 sets per exercise, 4-6 repetitions per set, and linear increases in intensity over time. As in similar RT studies, the training loads used will be individually progressed in a safe and effective manner in order to employ a progressive overload/challenge to the neuromuscular system and elicit the greatest training-induced neuromuscular adaptations possible. ;

Related Conditions & MeSH terms

• Cerebrovascular Function
• Cognitive Decline
• Cognitive Dysfunction

• NCT number: NCT03982550
• Study type: Interventional
• Source: University of Southern California
• Status: Completed
• Phase: N/A
• Start date: July 17, 2018
• Completion date: May 16, 2020