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Neuroimaging and Biochemical Markers in the Three Variants of Primary Progressive Aphasia

Gil-Navarro S.a · Lladó A.a, d · Rami L.a · Castellví M.a · Bosch B.a · Bargalló N.b, d · Lomeña F.c · Reñé R.e · Montagut N.a · Antonell A.a, d · Molinuevo J.L.a, d · Sánchez-Valle R.a, d
aAlzheimer’s Disease and Other Cognitive Disorders Unit, Department of Neurology, and Departments of bRadiology and cNuclear Medicine, Hospital Clínic, and dInstitut d’Investigació Biomédica August Pi I Sunyer (IDIBAPS), Barcelona, and eDepartment of Neurology, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Spain Dement Geriatr Cogn Disord 2013;35:106–117 (DOI:10.1159/000346289)


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.


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