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.

CONCLUSIONS: The novelty of the framework is its integration of disease stage, geriatric phenotype, peripheral metabolic response, and recovery into clinically actionable dose decisions rather than a universal lactate threshold. Prospective multicenter trials should standardize sampling, validate response thresholds, and determine whether this approach improves cognition, mobility, independence, safety, and caregiver-relevant outcomes beyond usual advice or fixed-dose exercise.