Neuroimaging and biochemical markers in the three variants of primary progressive aphasia

Dement Geriatr Cogn Disord. 2013;35(1-2):106-17. doi: 10.1159/000346289. Epub 2013 Feb 6.

Abstract

Background/aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level.

Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer's disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested.

Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion.

Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / psychology
  • Aphasia, Primary Progressive / metabolism
  • Aphasia, Primary Progressive / pathology*
  • Aphasia, Primary Progressive / psychology
  • Apolipoproteins E / blood
  • Biomarkers / blood*
  • Cohort Studies
  • DNA Repeat Expansion
  • Educational Status
  • Female
  • Genetic Markers
  • Genetic Variation
  • Humans
  • Image Processing, Computer-Assisted
  • Intercellular Signaling Peptides and Proteins / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging / methods*
  • Neuropsychological Tests
  • Progranulins
  • Socioeconomic Factors
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Apolipoproteins E
  • Biomarkers
  • GRN protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Progranulins