Determinants of Cognitive and Brain Resilience to Reduced Neuronal Metabolism in Alzheimer’s Disease: A Longitudinal Whole-Brain MRSI Study

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Motivation: The role of demographic and genetic factors in the relationship between neuronal metabolism and cognitive/brain resilience in AD is unclear. Goal(s): To identify factors (age, sex, APOE-ε4, education, and brain atrophy) that contribute to preserved cognition and brain structure despite reduced neuronal metabolism. Approach: We studied 150 participants (41 with MCI, 109 with AD), 27 with follow-ups, all undergoing whole-brain 1H-MRSI and cognitive assessments. Moderation effects of these factors on neuronal metabolism, cognitive decline, and cortical thinning were analyzed. Results: Education and brain volume moderated the impact of impaired neuronal metabolism on cognitive decline, with education enhancing brain resilience. Impact: Education and brain volume moderated the impact of impaired neuronal metabolism on cognitive decline, with education also moderated the effect on brain resilience. These findings suggest that education may be protective against cognitive decline and brain atrophy despite neuronal dysfunction.

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