Distinctive Neurochemistry in Alzheimer's Disease via 7 T in Vivo Magnetic Resonance Spectroscopy

Research output: Contribution to journalArticle

Abstract

This study's objective was to increase understanding of biological mechanisms underlying clinical Alzheimer's disease (AD) by noninvasively measuring an expanded neurochemical profile and exploring how well this advanced technology distinguishes AD from cognitively normal controls. We measured concentrations of 14 neurochemicals using ultra-high field (7 T) ultra-short echo time (8ms) magnetic resonance spectroscopy (MRS) in 16 participants with mild to moderate clinical AD and 33 age- and gender-matched control participants. MRS was localized to the posterior cingulate cortex (PCC), a region known to be impacted by AD, and the occipital cortex (OCC), a control region. Participants with AD were recruited from dementia specialty clinics. Concentration of the antioxidant ascorbate was higher (p<0.0007) in both brain regions. Concentrations of the glial marker myo-inositol and the choline-containing compounds involved in membrane turnover were higher (p≤0.0004) in PCC of participants with AD. Ascorbate and myo-inositol concentrations were strongly associated, especially in the PCC. Random forests, using the 14 neurochemicals in the two regions, distinguished participants with AD from controls: same-sample sensitivity and specificity were 88% and 97%, respectively, though out-of-sample-values would be lower. Ultra-high field ultra-short echo time MRS identified the co-occurrence of elevated ascorbate and myo-inositol in the PCC as markers that distinguish participants with mild to moderate AD from controls. While elevated myo-inositol may be a surrogate marker of neuroinflammation, the unexpected elevation of the antioxidant ascorbate may reflect infiltration of ascorbate-rich leukocytes.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalJournal of Alzheimer's Disease
Volume68
Issue number2
DOIs
StatePublished - Jan 1 2019

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Neurochemistry
Alzheimer Disease
Magnetic Resonance Spectroscopy
Gyrus Cinguli
Inositol
Antioxidants
Occipital Lobe
Alzheimer Disease 7
Choline
Neuroglia
Dementia
Leukocytes
Biomarkers
Technology
Sensitivity and Specificity
Membranes
Brain

Keywords

  • Ascorbate
  • myo -inositol
  • neurochemical profile
  • neuroinflammation
  • posterior cingulate cortex
  • ultra-high field
  • ultra-short echo time

PubMed: MeSH publication types

  • Journal Article

Cite this

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title = "Distinctive Neurochemistry in Alzheimer's Disease via 7 T in Vivo Magnetic Resonance Spectroscopy",
abstract = "This study's objective was to increase understanding of biological mechanisms underlying clinical Alzheimer's disease (AD) by noninvasively measuring an expanded neurochemical profile and exploring how well this advanced technology distinguishes AD from cognitively normal controls. We measured concentrations of 14 neurochemicals using ultra-high field (7 T) ultra-short echo time (8ms) magnetic resonance spectroscopy (MRS) in 16 participants with mild to moderate clinical AD and 33 age- and gender-matched control participants. MRS was localized to the posterior cingulate cortex (PCC), a region known to be impacted by AD, and the occipital cortex (OCC), a control region. Participants with AD were recruited from dementia specialty clinics. Concentration of the antioxidant ascorbate was higher (p<0.0007) in both brain regions. Concentrations of the glial marker myo-inositol and the choline-containing compounds involved in membrane turnover were higher (p≤0.0004) in PCC of participants with AD. Ascorbate and myo-inositol concentrations were strongly associated, especially in the PCC. Random forests, using the 14 neurochemicals in the two regions, distinguished participants with AD from controls: same-sample sensitivity and specificity were 88{\%} and 97{\%}, respectively, though out-of-sample-values would be lower. Ultra-high field ultra-short echo time MRS identified the co-occurrence of elevated ascorbate and myo-inositol in the PCC as markers that distinguish participants with mild to moderate AD from controls. While elevated myo-inositol may be a surrogate marker of neuroinflammation, the unexpected elevation of the antioxidant ascorbate may reflect infiltration of ascorbate-rich leukocytes.",
keywords = "Ascorbate, myo -inositol, neurochemical profile, neuroinflammation, posterior cingulate cortex, ultra-high field, ultra-short echo time",
author = "Malgorzata Marjanska and McCarten, {John R} and Hodges, {James S} and Hemmy, {Laura S} and Melissa Terpstra",
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AU - Terpstra, Melissa

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