Brain total creatine differs between primary progressive aphasia (PPA) subtypes and correlates with disease severity

Kathleen E. Hupfeld, Helge J. Zöllner, Georg Oeltzschner, Hayden W. Hyatt, Olivia Herrmann, Jessica Gallegos, Steve C.N. Hui, Ashley D. Harris, Richard A.E. Edden, Kyrana Tsapkini

Research output: Contribution to journalArticlepeer-review


Primary progressive aphasia (PPA) is comprised of three subtypes: logopenic (lvPPA), non-fluent (nfvPPA), and semantic (svPPA). We used magnetic resonance spectroscopy (MRS) to measure tissue-corrected metabolite levels in the left inferior frontal gyrus (IFG) and right sensorimotor cortex (SMC) from 61 PPA patients. We aimed to: (1) characterize subtype differences in metabolites; and (2) test for metabolite associations with symptom severity. tCr differed by subtype across the left IFG and right SMC. tCr levels were lowest in lvPPA and highest in svPPA. tCr levels predicted lvPPA versus svPPA diagnosis. Higher IFG tCr and lower Glx correlated with greater disease severity. As tCr is involved in brain energy metabolism, svPPA pathology might involve changes in specific cellular energy processes. Perturbations to cellular energy homeostasis in language areas may contribute to symptoms. Reduced cortical excitatory capacity (i.e. lower Glx) in language regions may also contribute to symptoms. Thus, tCr may be useful for differentiating between PPA subtypes, and both tCr and Glx might have utility in understanding PPA mechanisms and tracking progression.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalNeurobiology of aging
StatePublished - Feb 2023


  • Creatine (tCr)
  • Glutamate+glutamine (Glx)
  • Magnetic resonance spectroscopy (MRS)
  • Point RESolved Spectroscopy (PRESS)
  • Primary Progressive Aphasia (PPA)

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • Neuroscience(all)
  • Developmental Biology


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