Supplementary Material for: Neuroimaging and Biochemical Markers in the Three Variants of Primary Progressive Aphasia

<b><i>Background/Aim:</i></b> 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. <b><i>Methods:</i></b> 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, <i>APOE</i> genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. <b><i>Results:</i></b> 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 <i>GRN</i> mutation and 2 the <i>C9ORF72</i> hexanucleotide expansion. <b><i>Conclusions:</i></b> 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.