Lactate-Informed Exercise Prescription in Mild Cognitive Impairment and Alzheimer’s Disease: A Translational Framework for Preserving Cognition, Mobility, and Independence

Background

This narrative review proposes a conceptual, lactate-informed framework for individualized exercise prescription in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Exercise is recommended in these populations, but fixed external doses do not account for heterogeneity in disease stage, frailty, sarcopenia, cardiovascular risk, or recovery. Main Text: We integrate clinical exercise evidence, geriatric assessment, lactate physiology, muscle-brain signaling, implementation science, and trial methodology. The framework uses peripheral blood lactate as one component of a monitoring matrix with workload, heart rate, blood pressure, perceived exertion, fatigue recovery, gait safety, adherence, and caregiver support. Repeated, standardized lactate responses are classified as low, adaptive and recoverable, excessive, or non-interpretable/unsafe, prompting stepwise adjustment of aerobic, resistance, balance, and cognitive-motor training. Peripheral blood lactate is an internal-load marker; it does not directly quantify blood-brain barrier transport, CNS lactate kinetics, or target engagement. Mechanistic pathways involving monocarboxylate transport, HCAR1, BDNF/VEGF, myokines, and lactylation therefore remain hypotheses to be tested in humans with MCI or AD.