FDG-PET in the Diagnosis of Primary Progressive Aphasia

Introduction: Primary progressive aphasia (PPA) is a disease that is known to affect the frontal and temporal regions of the left hemisphere. In clinical practice, patients with PPA are divided into three subtypes: semantic dementia (SD), progressive nonfluent aphasia (PNFA), and logopenic progressive aphasia (LPA). Currently, the diagnosis of PPA is based on consensus guidelines such as Gorno-Tempini criteria. Although neuroimaging studies are needed to exclude other causes of aphasia such as stroke or tumor, they allow determination of the best approach for predicting pathology and diagnosis of the logopenic variant. Imaging criteria for PPA subtypes include changes in structure, metabolism, or perfusion in typical regions. Meta-analyses have shown disjunction between hypometabolism and atrophy in imaging studies on PPA, indicating the need for different diagnostic imaging criteria for 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) and for magnetic resonance imaging (MRI). PPA is often an early indication of future development of dementia, specifically SD for frontotemporal dementia (FTD) and LPA has been considered an atypical presentation of Alzheimer’s disease (AD), such that early identification of PPA can be very useful in patient management and prognosis. FDG-PET enables visualization of metabolic alteration preceding atrophy. As such, FDG-PET has been applied extensively to PPA to assess underlying metabolic dysfunction. However, differential diagnosis remains challenging as they share overlapped impaired regions, and misdiagnosis or delay of correct diagnosis is common, especially in patients with SD who are frequently diagnosed with AD. Therefore, the purpose of this review is to clarify the value of FDG-PET in the detection and diagnosis of PPA.

Methods: A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. All retrospective and prospective studies utilizing FDG-PET in patients with primary progressive aphasia were included. Included studies were screened for methodology quality assessment and extraction of results and outcomes.

Results: Previous studies have revealed alterations in regional glucose uptake in PPA patients. The three PPA subtypes show distinct patterns in FDG-PET imaging. Hypometabolism in the left thalamus and left inferior temporal gyrus, and the fusiform gyrus were reported in SD subtype. PNFA showed hypometabolism bilaterally in caudate nuclei, left hemisphere, thalamus, middle and superior temporal gyri, insula/inferior frontal gyrus, pars opercularis, lateral orbital gyrus, and middle frontal gyrus. LPA subtype showed hypometabolism in lateral temporoparietal and medial parietal lobes and left frontal lobe that differ from classical AD due to distinct atrophy patterns. These findings are complemented by concurrent findings of severe hypometabolism in the left temporal areas. Most studies have shown a more prominent decrease in left parietal activity compared to the left temporal lobe. The presence of glucose hypometabolism in the left angular, supramarginal, and posterosuperior temporal gyri in a significant percentage of patients shows that these regions are critical for the development of aphasia.

Conclusions: Neuroimaging studies of patients with PPA showed a promising role of FDG-PET scan as a diagnostic modality especially in differentiating the subtypes of PPA. The value of FDG-PET in the diagnosis of PPA is especially underscored given the challenge of accurate diagnosis and prediction of future development of frontotemporal dementia (FTD). Physicians should carefully consider PPA when reporting FDG-PET in patients with language problems. Future FDG-PET studies with larger patient populations and well-designed cohorts of PPA patients can improve our understanding of the disease and its related subclasses. Moreover, this knowledge can potentially identify opportunities for therapeutic developments and evaluation for PPA.