Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study

Abstract

Background: There is evidence that chronic exercise can benefit the brain, but the effects vary markedly between studies. One potential mechanism for exercise-related benefit is the increase in systemic lactate concentration that is well-characterized to occur during exercise. Lactate is known to cross the blood brain barrier and can be used readily as a fuel for neurons. This may be particularly important in Alzheimer's Disease, which is characterized by cerebral hypometabolism. However, little is known about how whole-body lactate metabolism differs between older adults and individuals with cognitive impairment. This information is critical when considering potential differences in responses to exercise in various cognitive diagnosis groups.

Methods: Here we describe the use of a "lactate clamp" procedure to adjust blood lactate levels to approximate those achieved during exercise, but while at rest. This trial will compare lactate oxidation between cognitively healthy older adults and cognitively impaired participants. We will further evaluate the effect of acute lactate infusion on cognitive performance.

Discussion: The findings of the study described here, the Lactate for Energy and Neurocognition trial (clinicaltrials.gov # NCT05207397) will add to our understanding of systemic lactate mechanics in cognitively healthy older adults and individuals with Alzheimer's Disease. These findings will be applicable to ongoing exercise trials and to future studies aimed at modulating systemic bioenergetic function in aging and Alzheimer's Disease.

Keywords: Alzheimer's disease; Brain; Exercise; Lactate; Metabolism.

Figure 1.. Schematic of the study visit timeline.

Figure 1A describes procedures prior to start of lactate infusion including consent, DXA, IV placement, baseline cogntitive test, sample collection, and infusate bolus. Figure 1B describes procedure timeline during lactate infusion which includes sample collection, breath collection, and second cognitive test. Additional information on amount of blood drawn and blood tube type at each collection time can be found in Figure 2.

Figure 2.. Detailed sample collection.

Blood tubes with different anticoagulants and volumes are used to collect samples throughout the study visit. Details for sample processing and analyses are described in sections of 2.5.1-2.5.4.