Presentation
Search Abstracts | Symposia | Slide Sessions | Poster Sessions | Poster Slams
Brain total creatine differs between Primary Progressive Aphasia (PPA) subtypes and correlates with disease severity
Poster A29 in Poster Session A, Thursday, October 6, 10:15 am - 12:00 pm EDT, Millennium Hall
Kathleen Hupfeld1,2, Helge Zöllner1,2, Georg Oeltzschner1,2, Hayden Hyatt1, Olivia Herrmann1, Jessica Gallegos1, Steve Hui1,2, Ashley Harris3,4, Richard Edden1,2, Kyrana Tsapkini1,5; 1Johns Hopkins University School of Medicine, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, 3Hotchkiss Brain Institute, University of Calgary, 4Alberta Children’s Hospital Research Institute, University of Calgary, 5Johns Hopkins University
Primary progressive aphasia (PPA) is a debilitating neurodegenerative disease that primarily impairs language function. It is comprised of three subtypes with varied clinical presentation and cortical atrophy patterns: logopenic variant (lvPPA), non-fluent variant (nfvPPA), and semantic variant (svPPA). No prior work has examined differences in brain chemistry between the PPA subtypes, or associations of brain chemistry with symptom severity. In the present work, we collected magnetic resonance spectroscopy (MRS) data in a main language production region, the left inferior frontal gyrus (IFG), and a control region, the right sensorimotor cortex (SMC) from 61 patients with PPA (ClinicalTrials.gov identifiers: NCT02606422, NCT03887481, and NCT04122001). Brain metabolite levels of total N-acetylaspartate (tNAA), total choline (tCho), total creatine (tCr), and glutamate+glutamine (Glx) were measured with conventional MRS, and gamma-aminobutyric acid (GABA) was measured using MEGA-PRESS. All data were processed using a state-of-the-art MRS analysis pipeline (Osprey), which generated tissue- and relaxation-corrected metabolite levels to account for the effects of cortical atrophy and other tissue-specific properties. We aimed to: 1) characterize differences between PPA subtypes for the 5 brain metabolites: tNAA, tCho, tCr, Glx, and GABA; and 2) test for associations between these neurometabolites and PPA symptom severity. We found that tCr levels differed by PPA subtype across both the left IFG and right SMC. In both regions, tCr levels were lowest among lvPPA patients and highest among svPPA patients. Moreover, across the whole cohort, higher tCr and lower Glx levels in the left IFG correlated with greater disease severity. Global atrophy (i.e., total intracerebral volume divided by total intracranial volume) did not differ by PPA subtype or correlate with tCr or Glx concentrations, suggesting that these effects were not dependent upon overall cortical atrophy. Given that tCr is involved in brain energy metabolism and homeostasis, our results indicate that svPPA pathology might involve perturbations to specific cellular energy processes. Our finding that higher tCr was associated with worse PPA symptom severity suggests that perturbations to cellular energy homeostasis in cortical language areas may contribute to PPA symptoms. In addition, reduced cortical excitatory capacity (i.e., lower Glx) in brain areas related to language processing may also contribute to PPA symptoms. Together, these findings suggest that tCr could serve as a biomarker to differentiate between PPA subtypes, and that both tCr and Glx might have utility for better understanding PPA disease mechanisms and tracking disease progression. Our forthcoming work will expand upon these findings, investigating whether and how these neurometabolites change in response to neuromodulation (transcranial direct current stimulation, tDCS) combined with language therapy in a double-blind randomized controlled trial.
Topic Areas: Disorders: Acquired, Language Therapy