Rationale and methods to characterize the acute exercise response in aging and Alzheimer's Disease: the AEROBIC pilot study

Abstract

There is evidence that exercise benefits the brain, but the mechanisms for this benefit are unclear. The chronic benefits of exercise are likely a product of discreet, acute responses in exercise-related blood biomarkers and brain metabolism. This acute exercise response has not been compared in aging and Alzheimer's Disease (AD). It is known that acute exercise elicits a powerful peripheral response in young individuals, and exercise-related biomarkers such as glucose and lactate readily penetrate the brain. How this changes with aging and neurodegenerative disease is less clear. It is critical to characterize and understand the acute effects of exercise, including different exercise intensities, in terms of the peripheral metabolic response and relationship with brain metabolism. This will help determine potential mechanisms for brain benefits of exercise and better inform the design of future clinical trials. The primary goal of the AEROBIC study is to characterize the acute exercise response of brain glucose metabolism and exercise-related blood biomarkers. We will measure how cerebral metabolism is affected by an acute bout of moderate and higher intensity exercise and characterize the extent to which this differs between cognitively healthy older adults and individuals with AD. Related to this primary goal, we will quantify the peripheral biomarker response to moderate and higher intensity exercise and how this relates to brain metabolic change in both groups.

Keywords: Alzheimer's Disease; Biomarker; Exercise; Lactate; Metabolism.

Fig. 1.

Schematic study flow diagram for the AEROBIC study. Individuals undergo a phone screen and subsequent GXT evaluation to screen for exclusion criteria, safety issues, and to identify the correct exercise dose to be administered for each participant during the PET exercise visit. Further evaluation is performed to evaluate cognitive status for each indivdiual prior to undergoing resting and exercise PET scans. An MRI scan is performed as the last study visit to allow for coregistration of PET images onto the structural MRI for each participant. GXT; graded exercise test, CDR; clinical dementia rating, DX; diagnosis, PET; positron emission topography, MRI; magnetic resonance imaging.

Fig. 2.

Detailed timeline of procedures during the (A) “Resting” and (B) “Exercise” PET visits. Strict timings are adhered to regarding blood draws, radiotracer uptake, and administration of cognitive tests (NIH toolbox).

Fig. 3.

Schematic diagram that demonstrates administration of each exercise intensity during the “Exercise” PET visit.