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

Orit H. Lesman-Segev; Renaud La Joie; Leonardo Iaccarino; Iryna Lobach; Howard J. Rosen; Sang Won Seo; Mustafa Janabi; Suzanne L. Baker; Lauren Edwards; Julie Pham; John Olichney; Adam Boxer; Eric Huang; Marilu Gorno-Tempini; Charles DeCarli; Mackenzie Hepker; Ji Hye L. Hwang; Bruce L. Miller; Salvatore Spina; Lea T. Grinberg; William W. Seeley; William J. Jagust; Gil D. Rabinovici

doi:10.1002/ana.25968

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

Orit H. Lesman-Segev, Renaud La Joie, Leonardo Iaccarino, Iryna Lobach, Howard J. Rosen, Sang Won Seo, Mustafa Janabi, Suzanne L. Baker, Lauren Edwards, Julie Pham, John Olichney, Adam Boxer, Eric Huang, Marilu Gorno-Tempini, Charles DeCarli, Mackenzie Hepker, Ji Hye L. Hwang, Bruce L. Miller, Salvatore Spina, Lea T. GrinbergWilliam W. Seeley, William J. Jagust, Gil D. Rabinovici

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem ¹¹C-Pittsburgh compound B (PIB) and ¹⁸F-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 2020.

Original language	English (US)
Journal	Annals of Neurology
DOIs	https://doi.org/10.1002/ana.25968
State	Accepted/In press - 2020

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Lesman-Segev, O. H., La Joie, R., Iaccarino, L., Lobach, I., Rosen, H. J., Seo, S. W., Janabi, M., Baker, S. L., Edwards, L., Pham, J., Olichney, J., Boxer, A., Huang, E., Gorno-Tempini, M., DeCarli, C., Hepker, M., Hwang, J. H. L., Miller, B. L., Spina, S., ... Rabinovici, G. D. (Accepted/In press). Diagnostic Accuracy of Amyloid versus ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia. Annals of Neurology. https://doi.org/10.1002/ana.25968

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

In: Annals of Neurology, 2020.

Research output: Contribution to journal › Article › peer-review

Lesman-Segev, OH, La Joie, R, Iaccarino, L, Lobach, I, Rosen, HJ, Seo, SW, Janabi, M, Baker, SL, Edwards, L, Pham, J, Olichney, J, Boxer, A, Huang, E, Gorno-Tempini, M, DeCarli, C, Hepker, M, Hwang, JHL, Miller, BL, Spina, S, Grinberg, LT, Seeley, WW, Jagust, WJ & Rabinovici, GD 2020, 'Diagnostic Accuracy of Amyloid versus ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia', Annals of Neurology. https://doi.org/10.1002/ana.25968

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. / Diagnostic Accuracy of Amyloid versus ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia. In: Annals of Neurology. 2020.

@article{fea0bfc17a284a999cb2462352a41f0d,

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

abstract = "Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem 11C-Pittsburgh compound B (PIB) and 18F-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 2020.",

author = "Lesman-Segev, {Orit H.} and {La Joie}, Renaud and Leonardo Iaccarino and Iryna Lobach and Rosen, {Howard J.} and Seo, {Sang Won} and Mustafa Janabi and Baker, {Suzanne L.} and Lauren Edwards and Julie Pham and John Olichney and Adam Boxer and Eric Huang and Marilu Gorno-Tempini and Charles DeCarli and Mackenzie Hepker and Hwang, {Ji Hye L.} and Miller, {Bruce L.} and Salvatore Spina and Grinberg, {Lea T.} and Seeley, {William W.} and Jagust, {William J.} and Rabinovici, {Gil D.}",

note = "Funding Information: The study was supported by the NIH/National Institute on Aging (R01‐AG045611, P01‐AG1972403, P50‐AG023501, P30‐AG010129, R01‐AG032306, K24‐AG053435, R01‐AG038791, K08‐AG052648, K99AG065501), Alzheimerʼs Association (AARF‐16‐443577), Bluefield Project to Cure FTD, and Rainwater Charitable Foundation. ",

year = "2020",

doi = "10.1002/ana.25968",

language = "English (US)",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Diagnostic Accuracy of Amyloid versus 18F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia

AU - Lesman-Segev, Orit H.

AU - La Joie, Renaud

AU - Iaccarino, Leonardo

AU - Lobach, Iryna

AU - Rosen, Howard J.

AU - Seo, Sang Won

AU - Janabi, Mustafa

AU - Baker, Suzanne L.

AU - Edwards, Lauren

AU - Pham, Julie

AU - Olichney, John

AU - Boxer, Adam

AU - Huang, Eric

AU - Gorno-Tempini, Marilu

AU - DeCarli, Charles

AU - Hepker, Mackenzie

AU - Hwang, Ji Hye L.

AU - Miller, Bruce L.

AU - Spina, Salvatore

AU - Grinberg, Lea T.

AU - Seeley, William W.

AU - Jagust, William J.

AU - Rabinovici, Gil D.

N1 - Funding Information: The study was supported by the NIH/National Institute on Aging (R01‐AG045611, P01‐AG1972403, P50‐AG023501, P30‐AG010129, R01‐AG032306, K24‐AG053435, R01‐AG038791, K08‐AG052648, K99AG065501), Alzheimerʼs Association (AARF‐16‐443577), Bluefield Project to Cure FTD, and Rainwater Charitable Foundation.

PY - 2020

Y1 - 2020

N2 - Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem 11C-Pittsburgh compound B (PIB) and 18F-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 2020.

AB - Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem 11C-Pittsburgh compound B (PIB) and 18F-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 2020.

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