Diagnostic Accuracy of Amyloid versus 18 F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia

• Published in: Annals of neurology 2021-02, Vol.89 (2), p.389-401
• Main Authors: Lesman-Segev, Orit H, La Joie, Renaud, Iaccarino, Leonardo, Lobach, Iryna, Rosen, Howard J, Seo, Sang Won, Janabi, Mustafa, Baker, Suzanne L, Edwards, Lauren, Pham, Julie, Olichney, John, Boxer, Adam, Huang, Eric, Gorno-Tempini, Marilu, DeCarli, Charles, Hepker, Mackenzie, Hwang, Ji-Hye L, Miller, Bruce L, Spina, Salvatore, Grinberg, Lea T, Seeley, William W, Jagust, William J, Rabinovici, Gil D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Aniline Compounds; Autopsy; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; DNA-Binding Proteins - metabolism; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia - diagnostic imaging; Frontotemporal Dementia - metabolism; Frontotemporal Dementia - pathology; Frontotemporal Lobar Degeneration - diagnostic imaging; Frontotemporal Lobar Degeneration - metabolism; Frontotemporal Lobar Degeneration - pathology; Humans; Male; Middle Aged; Pick Disease of the Brain - diagnostic imaging; Pick Disease of the Brain - metabolism; Pick Disease of the Brain - pathology; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Plaque, Amyloid - psychology; Positron-Emission Tomography - methods; Radiopharmaceuticals; Sensitivity and Specificity; tau Proteins - metabolism; Thiazoles
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.25968

The purpose of this study was to compare the diagnostic accuracy of antemortem C-Pittsburgh compound B (PIB) and F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients. One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information. PIB PET was rated as positive or negative for cortical retention, whereas FDG scans were read as showing an Alzheimer disease (AD) or non-AD pattern. Neuropathological diagnoses were assigned using research criteria. Majority visual reads were compared to intermediate-high AD neuropathological change (ADNC). One hundred one participants were included (mean age = 67.2 years, 41 females, Mini-Mental State Examination = 21.9, PET-to-autopsy interval = 4.4 years). At autopsy, 32 patients showed primary AD, 56 showed non-AD neuropathology (primarily frontotemporal lobar degeneration [FTLD]), and 13 showed mixed AD/FTLD pathology. PIB showed higher sensitivity than FDG for detecting intermediate-high ADNC (96%, 95% confidence interval [CI] = 89-100% vs 80%, 95% CI = 68-92%, p = 0.02), but equivalent specificity (86%, 95% CI = 76-95% vs 84%, 95% CI = 74-93%, p = 0.80). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% (95% CI = 92-100%) and specificity was 98% (95% CI = 93-100%). Nine of 24 patients with incongruent reads were found to have co-occurrence of AD and non-AD pathologies. In our sample enriched for younger onset cognitive impairment, PIB-PET had higher sensitivity than FDG-PET for intermediate-high ADNC, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, whereas mixed pathology should be considered when PIB and FDG are incongruent. ANN NEUROL 2021;89:389-401.