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

Abstract

Objective: 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 intermediate-high 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. ANN NEUROL 2021;89:389-401.

Figure 1:. Study design

Abbreviations: PIB – ¹¹C- Pittsburgh compound B; FDG – ¹⁸F-fluorodeoxyglucose; AD – Alzheimer’s disease, ADNC – Alzheimer’s disease neuropathological changes; CDR – Clinical Dementia Rating; APOE e4 – Apolipoprotein E e4

Figure 2:. PIB, FDG and pathology in representative patients:

Patient 1 had a clinical diagnosis of AD, a positive PIB scan and an AD pattern of hypometabolism on FDG. Selected pathological slices from the hippocampus show neurofibrillary tangles, tau-positive neurites and threads and amyloid-beta plaques. Pathological diagnosis was AD with high ADNC. Patient 2 had a clinical diagnosis of bvFTD, a negative PIB scan and a non-AD pattern of hypometabolism on FDG. Selected pathological slice from the amygdala stained for tau shows Pick bodies. Pathological diagnosis was Pick’s disease. Patient 3 had a clinical diagnosis of semantic-variant primary progressive aphasia, PIB was positive and a non-AD pattern of hypometabolism was seen on FDG. Selected pathological slices show neurofibrillary tangles and threads in hippocampus, amyloid plaques in superior/middle temporal gyrus and TDP-43 positive dystrophic neurites in anterior cingulate cortex. Primary pathological diagnosis was FTLD-TDP43, type C and the contributing pathology was AD with intermediate ADNC. Immunohistochemical preparations are shown with magnification X20; Scale bar indicates 100 microns. Abbreviations: PIB – ¹¹C- Pittsburgh compound B; FDG – ¹⁸F fluorodeoxyglucose; AD – Alzheimer’s disease; bvFTD – behavioral variant frontotemporal dementia; FTD – Frontotemporal dementia; NFT – Neurofibrillary tangles; ADNC – Alzheimer’s disease neuropathological changes; PPA – Primary progressive aphasia; TDP - TAR DNA-binding protein; FTLD – Frontotemporal lobar degeneration; SUVR - standardized uptake value ; DVR – distribution volume ratio; Dx – Diagnosis

Figure 3:. Agreement between PIB and FDG reads

Abbreviation: PIB – ¹¹C-Pittsburgh compound B; FDG – ¹⁸F-fluorodeoxyglucose; AD – Alzheimer’s disease; PPV – Positive predictive value; NPV - Negative predictive value; CI – Confidence interval