title: Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive Impairment.
abstract: 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.
authors.affiliation: Department of Radiology, University of Washington, P.O. Box 357115, Seattle, WA 98195, USA ; Integrated Brain Imaging Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kurt E
authors.initials: KE
authors.lastname: Weaver
authors.affiliation: Department of Radiology, University of Washington, P.O. Box 357115, Seattle, WA 98195, USA ; Integrated Brain Imaging Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Richards
authors.affiliation: Department of Psychosocial and Community Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Logsdon
authors.affiliation: Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: McGough
authors.affiliation: Department of Radiology, University of Washington, P.O. Box 357115, Seattle, WA 98195, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Aylward
authors.affiliation: Department of Radiology, University of Washington, P.O. Box 357115, Seattle, WA 98195, USA ; Integrated Brain Imaging Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Kleinhans
authors.affiliation: Department of Radiology, University of Washington, P.O. Box 357115, Seattle, WA 98195, USA ; Integrated Brain Imaging Center, University of Washington, Seattle, WA 98195, USA ; Department of Neurology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Grabowski
authors.affiliation: Department of Psychosocial and Community Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: McCurry
authors.affiliation: Department of Psychosocial and Community Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Teri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019344:Lactic Acid / Q000032:analysis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male
chemical_list: D015415:Biomarkers; D019344:Lactic Acid