Diagnostic Accuracy of Amyloid versus¹⁸F‐Fluorodeoxyglucose Positron Emission Tomography inAutopsy‐ConfirmedDementia

Abstract

The purpose of this study was to compare the diagnostic accuracy of antemortem 11 C-Pittsburgh compound B (PIB) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients. Methods: 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 intermediatehigh AD neuropathological change (ADNC). Results: 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. Interpretation: 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.

Neuroimaging in Frontotemporal Dementia: Heterogeneity and Relationships with Underlying Neuropathology

“…Indeed, multiple groups have reported cases with amyloid-PET positivity in patients with an FTD syndrome who also showed typical FTD-like patterns of atrophy or glucose metabolism (not the posterior, temporo-parietal pattern of degeneration seen in AD). In these cases, autopsy typically showed mixed neuropathology, with the co-occurrence of FTLD and AD [213][214][215].…”

Depressive Pseudodementia with Reversible AD-like Brain Hypometabolism: A Case Report and a Review of the Literature

“…It has been generally accepted that such a pattern of hypometabolism predates structural changes. However, its suboptimal specificity for AD (estimated at 84% in a recent neuropathology-confirmed series [ 20 ]) may partially explain why it was initially also observed in our case, which also suggests that considering FDG-PET as a marker of neurodegeneration in AD-like cognitive impairment might be questionable.…”

Discordance and Concordance Between Cerebrospinal and [ 18 F]FDG-PET Biomarkers in Assessing Atypical and Early-Onset AD Dementia Cases

“…Another study evaluated the congruence/incongruence between amyloid-PET and [ 18 F] FDG-PET in autopsy-confirmed cohort. 39 Its target sample was similar to our study (early-onset and atypical clinical presentation). This study reported that the congruence of amyloid-PET and [ 18 F]FDG-PET biomarkers in detecting AD pathology was high (sensitivity and specificity more than 90%) when assessed at later stage with overt clinical symptoms, compared with early disease stage.…”