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

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.

背景与目的：探究各类原发性进行性失语（primary progressive aphasia, PPA）亚型中，个体层面当前临床与神经影像学标准同生化/遗传标志物之间的关联。方法：将32例PPA患者分为非流利型/语法缺失型（non-fluent/agrammatic, nfvPPA）、语义型（semantic, svPPA）、找词困难型（logopenic variant, lvPPA）以及未分类型（unclassifiable, uPPA）。对所有患者，我们评估了各亚型对应的神经影像学标准（磁共振成像及/或单光子发射计算机断层扫描/正电子发射断层扫描），并检测了血清颗粒蛋白前体（progranulin）水平、载脂蛋白E（APOE）基因型，以及阿尔茨海默病（Alzheimer’s disease, AD）脑脊液（cerebrospinal fluid, CSF）生物标志物。存在一级亲属早发性痴呆家族史的病例接受了基因检测。结果：15例非流利型/语法缺失型PPA患者中10例（66%）、5例语义型PPA患者全部（100%）、7例找词困难型PPA患者全部（100%）满足至少1项经神经影像学支持的诊断标准。所有找词困难型PPA患者与3/5（60%）未分类型PPA患者均检出AD-CSF生物标志物，而非流利型/语法缺失型与语义型PPA患者均未检出此类标志物。4例（27%）非流利型/语法缺失型PPA患者携带致痴呆突变：2例存在GRN基因突变（GRN mutation），2例存在C9ORF72六核苷酸重复扩增（C9ORF72 hexanucleotide expansion）。结论：语义型与找词困难型PPA的临床标准同经神经影像学支持的生物标志物之间存在极佳的相关性，且找词困难型PPA的临床标准还与AD-CSF生化标志物存在相关性。非流利型/语法缺失型PPA的神经影像学、生化及遗传学检测结果存在异质性。将生化/遗传标志物纳入PPA临床诊断体系，可帮助临床医师更准确地预测PPA患者的神经病理类型，尤其针对非流利型/语法缺失型与未分类型PPA病例。