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.

<b><i>背景与研究目的：</i></b> 本研究旨在从个体层面探讨原发性进行性失语（primary progressive aphasia, PPA）各亚型的现行临床与神经影像诊断标准，以及其与生化、遗传标志物之间的关联。<b><i>研究方法：</i></b> 本研究纳入32例PPA患者，将其分为非流利型/语法缺失型（non-fluent/agrammatic, nfvPPA）、语义型（semantic, svPPA）、找词困难型（logopenic variant, lvPPA）及未分类型（unclassifiable, uPPA）四类。对所有患者，我们评估各亚型对应的神经影像诊断标准[包括磁共振成像（magnetic resonance imaging）和/或单光子发射计算机断层扫描（single photon emission computed tomography）/正电子发射断层扫描（positron emission tomography）]，并检测其血清颗粒蛋白前体（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。对于存在早发性痴呆一级亲属家族史的病例，我们开展了基因检测。<b><i>研究结果：</i></b> 15例nfvPPA患者中10例（66%）、5例svPPA患者全部（100%）以及7例lvPPA患者全部（100%）至少符合1项经神经影像支持的诊断标准。所有lvPPA患者与5例uPPA患者中的3例（60%）检出AD-CSF生物标志物，而nfvPPA及svPPA患者均未检出此类标志物。4例（27%）nfvPPA患者携带致痴呆突变：其中2例携带有GRN基因突变，另外2例携带有C9ORF72六核苷酸重复扩增。<b><i>研究结论：</i></b> svPPA与lvPPA的临床诊断标准与经神经影像支持的生物标志物之间存在极佳的相关性，lvPPA的临床标准与AD-CSF生化标志物亦存在此类关联。nfvPPA的神经影像、生化及遗传学检测结果呈现显著异质性。将生化、遗传标志物纳入PPA临床诊断体系，可帮助临床医师更精准地预测PPA患者的神经病理类型，尤其针对nfvPPA与uPPA病例。