Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive Impairment

Mitochondrial dysfunction represents a central factor within the pathogenesis of the Alzheimer's disease (AD) spectrum. We hypothesized that in vivo measurements of lactate (lac), a by-product of glycolysis, would correlate with functional impairment and measures of brain health in a cohort of 15 amnestic mild cognitive impairment (aMCI) individuals. Lac was quantified from the precuneus/posterior cingulate (PPC) using 2-dimensional J-resolved magnetic resonance spectroscopy (MRS). Additionally, standard behavioral and imaging markers of aMCI disease progression were acquired. PPC lac was negatively correlated with performance on the Wechsler logical memory tests and on the minimental state examination even after accounting for gray matter, cerebral spinal fluid volume, and age. No such relationships were observed between lac and performance on nonmemory tests. Significant negative relationships were also noted between PPC lac and hippocampal volume and PPC functional connectivity. Together, these results reveal that aMCI individuals with a greater disease progression have increased concentrations of PPC lac. Because lac is upregulated as a compensatory response to mitochondrial impairment, we propose that J-resolved MRS of lac is a noninvasive, surrogate biomarker of impaired metabolic function and would provide a useful means of tracking mitochondrial function during therapeutic trials targeting brain metabolism.