Abstract
Mild cognitive impairment (MCI) is associated with cerebral glucose hypometabolism and an increased risk of progression to Alzheimer’s disease (AD). Altered lactate metabolism may represent an additional component of this metabolic vulnerability. We propose the Dual-Fuel Hypothesis as a testable framework linking glucose-related metabolism with lactate-dependent energy and signaling pathways, while recognizing that this pathway has not been directly tested in MCI. This narrative review was guided by the SANRA framework. Structured screening was conducted specifically for randomized exercise-intervention studies in MCI, identifying 35 publications representing 29 independent cohorts. Evidence consistently supports impaired cerebral glucose metabolism in MCI due to AD, whereas alterations in lactate homeostasis and transport remain less clearly defined. Exercise improves systemic glucose utilization and increases circulating lactate, particularly during vigorous intensity aerobic and resistance exercise. Several trials reported favorable cognitive or neuroimaging outcomes, although larger or longer trials did not consistently show significant between-group cognitive benefits. No identified MCI exercise trial has concurrently measured exercise-induced lactate, cerebral substrate utilization, and cognition.