Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography

Keith A. Josephs; Nirubol Tosakulwong; Rodolfo G. Gatto; Stephen D. Weigand; Farwa Ali; Hugo Botha; Jonathan Graff-Radford; Mary M. Machulda; Rodolfo Savica; Christopher G. Schwarz; Matthew L. Senjem; Bradley F. Boeve; Kejal Kantarci; David T. Jones; Vijay K. Ramanan; Julie A. Fields; Ross R. Reichard; Dennis W. Dickson; Ronald C. Petersen; Clifford R. Jack; Val J. Lowe; Jennifer L. Whitwell

doi:10.1002/ana.26479

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography

Keith A. Josephs, Nirubol Tosakulwong, Rodolfo G. Gatto, Stephen D. Weigand, Farwa Ali, Hugo Botha, Jonathan Graff-Radford, Mary M. Machulda, Rodolfo Savica, Christopher G. Schwarz, Matthew L. Senjem, Bradley F. Boeve, Kejal Kantarci, David T. Jones, Vijay K. Ramanan, Julie A. Fields, Ross R. Reichard, Dennis W. Dickson, Ronald C. Petersen, Clifford R. JackVal J. Lowe, Jennifer L. Whitwell

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

Abstract

Objective: This study was undertaken to assess cross-sectional and longitudinal [¹⁸F]-flortaucipir positron emission tomography (PET) uptake in pathologically confirmed frontotemporal lobar degeneration (FTLD) and to compare FTLD to cases with high and low levels of Alzheimer disease (AD) neuropathologic changes (ADNC). Methods: One hundred forty-three participants who had completed at least one flortaucipir PET and had autopsy-confirmed FTLD (n = 52) or high (n = 58) or low ADNC (n = 33) based on Braak neurofibrillary tangle stages 0–IV versus V–VI were included. Flortaucipir standard uptake value ratios (SUVRs) were calculated for 9 regions of interest (ROIs): an FTLD meta-ROI, midbrain, globus pallidum, an AD meta-ROI, entorhinal, inferior temporal, orbitofrontal, precentral, and medial parietal. Linear mixed effects models were used to compare mean baseline SUVRs and annual rate of change in SUVR by group. Sensitivity and specificity to distinguish FTLD from high and low ADNC were calculated. Results: Baseline uptake in the FTLD meta-ROI, midbrain, and globus pallidus was greater in FTLD than high and low ADNC. No region showed a greater rate of flortaucipir accumulation in FTLD. Baseline uptake in the AD-related regions and orbitofrontal and precentral cortices was greater in high ADNC, and all showed greater rates of accumulation compared to FTLD. Baseline differences were superior to longitudinal rates in differentiating FTLD from high and low ADNC. A simple baseline metric of midbrain/inferior temporal ratio of flortaucipir uptake provided good to excellent differentiation between FTLD and high and low ADNC (sensitivities/specificities = 94%/95% and 71%/70%). Interpretation: There are cross-sectional and longitudinal differences in flortaucipir uptake between FTLD and high and low ADNC. However, optimum differentiation between FTLD and ADNC was achieved with baseline uptake rather than longitudinal rates. ANN NEUROL 2022;92:1016–1029.

Original language	English (US)
Pages (from-to)	1016-1029
Number of pages	14
Journal	Annals of neurology
Volume	92
Issue number	6
DOIs	https://doi.org/10.1002/ana.26479
State	Published - Dec 2022

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Josephs, K. A., Tosakulwong, N., Gatto, R. G., Weigand, S. D., Ali, F., Botha, H., Graff-Radford, J., Machulda, M. M., Savica, R., Schwarz, C. G., Senjem, M. L., Boeve, B. F., Kantarci, K., Jones, D. T., Ramanan, V. K., Fields, J. A., Reichard, R. R., Dickson, D. W., Petersen, R. C., ... Whitwell, J. L. (2022). Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography. Annals of neurology, 92(6), 1016-1029. https://doi.org/10.1002/ana.26479

Josephs, KA, Tosakulwong, N, Gatto, RG, Weigand, SD, Ali, F , Botha, H , Graff-Radford, J , Machulda, MM , Savica, R , Schwarz, CG, Senjem, ML, Boeve, BF , Kantarci, K , Jones, DT, Ramanan, VK, Fields, JA, Reichard, RR, Dickson, DW , Petersen, RC , Jack, CR , Lowe, VJ & Whitwell, JL 2022, 'Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography', Annals of neurology, vol. 92, no. 6, pp. 1016-1029. https://doi.org/10.1002/ana.26479

@article{cda6e6fac26f45ffa03ae32a41ab676b,

title = "Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography",

abstract = "Objective: This study was undertaken to assess cross-sectional and longitudinal [18F]-flortaucipir positron emission tomography (PET) uptake in pathologically confirmed frontotemporal lobar degeneration (FTLD) and to compare FTLD to cases with high and low levels of Alzheimer disease (AD) neuropathologic changes (ADNC). Methods: One hundred forty-three participants who had completed at least one flortaucipir PET and had autopsy-confirmed FTLD (n = 52) or high (n = 58) or low ADNC (n = 33) based on Braak neurofibrillary tangle stages 0–IV versus V–VI were included. Flortaucipir standard uptake value ratios (SUVRs) were calculated for 9 regions of interest (ROIs): an FTLD meta-ROI, midbrain, globus pallidum, an AD meta-ROI, entorhinal, inferior temporal, orbitofrontal, precentral, and medial parietal. Linear mixed effects models were used to compare mean baseline SUVRs and annual rate of change in SUVR by group. Sensitivity and specificity to distinguish FTLD from high and low ADNC were calculated. Results: Baseline uptake in the FTLD meta-ROI, midbrain, and globus pallidus was greater in FTLD than high and low ADNC. No region showed a greater rate of flortaucipir accumulation in FTLD. Baseline uptake in the AD-related regions and orbitofrontal and precentral cortices was greater in high ADNC, and all showed greater rates of accumulation compared to FTLD. Baseline differences were superior to longitudinal rates in differentiating FTLD from high and low ADNC. A simple baseline metric of midbrain/inferior temporal ratio of flortaucipir uptake provided good to excellent differentiation between FTLD and high and low ADNC (sensitivities/specificities = 94%/95% and 71%/70%). Interpretation: There are cross-sectional and longitudinal differences in flortaucipir uptake between FTLD and high and low ADNC. However, optimum differentiation between FTLD and ADNC was achieved with baseline uptake rather than longitudinal rates. ANN NEUROL 2022;92:1016–1029.",

author = "Josephs, {Keith A.} and Nirubol Tosakulwong and Gatto, {Rodolfo G.} and Weigand, {Stephen D.} and Farwa Ali and Hugo Botha and Jonathan Graff-Radford and Machulda, {Mary M.} and Rodolfo Savica and Schwarz, {Christopher G.} and Senjem, {Matthew L.} and Boeve, {Bradley F.} and Kejal Kantarci and Jones, {David T.} and Ramanan, {Vijay K.} and Fields, {Julie A.} and Reichard, {Ross R.} and Dickson, {Dennis W.} and Petersen, {Ronald C.} and Jack, {Clifford R.} and Lowe, {Val J.} and Whitwell, {Jennifer L.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2022",

month = dec,

doi = "10.1002/ana.26479",

language = "English (US)",

volume = "92",

pages = "1016--1029",

journal = "Annals of neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "6",

}

TY - JOUR

T1 - Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography

AU - Josephs, Keith A.

AU - Tosakulwong, Nirubol

AU - Gatto, Rodolfo G.

AU - Weigand, Stephen D.

AU - Ali, Farwa

AU - Botha, Hugo

AU - Graff-Radford, Jonathan

AU - Machulda, Mary M.

AU - Savica, Rodolfo

AU - Schwarz, Christopher G.

AU - Senjem, Matthew L.

AU - Boeve, Bradley F.

AU - Kantarci, Kejal

AU - Jones, David T.

AU - Ramanan, Vijay K.

AU - Fields, Julie A.

AU - Reichard, Ross R.

AU - Dickson, Dennis W.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

AU - Lowe, Val J.

AU - Whitwell, Jennifer L.

PY - 2022/12

Y1 - 2022/12

N2 - Objective: This study was undertaken to assess cross-sectional and longitudinal [18F]-flortaucipir positron emission tomography (PET) uptake in pathologically confirmed frontotemporal lobar degeneration (FTLD) and to compare FTLD to cases with high and low levels of Alzheimer disease (AD) neuropathologic changes (ADNC). Methods: One hundred forty-three participants who had completed at least one flortaucipir PET and had autopsy-confirmed FTLD (n = 52) or high (n = 58) or low ADNC (n = 33) based on Braak neurofibrillary tangle stages 0–IV versus V–VI were included. Flortaucipir standard uptake value ratios (SUVRs) were calculated for 9 regions of interest (ROIs): an FTLD meta-ROI, midbrain, globus pallidum, an AD meta-ROI, entorhinal, inferior temporal, orbitofrontal, precentral, and medial parietal. Linear mixed effects models were used to compare mean baseline SUVRs and annual rate of change in SUVR by group. Sensitivity and specificity to distinguish FTLD from high and low ADNC were calculated. Results: Baseline uptake in the FTLD meta-ROI, midbrain, and globus pallidus was greater in FTLD than high and low ADNC. No region showed a greater rate of flortaucipir accumulation in FTLD. Baseline uptake in the AD-related regions and orbitofrontal and precentral cortices was greater in high ADNC, and all showed greater rates of accumulation compared to FTLD. Baseline differences were superior to longitudinal rates in differentiating FTLD from high and low ADNC. A simple baseline metric of midbrain/inferior temporal ratio of flortaucipir uptake provided good to excellent differentiation between FTLD and high and low ADNC (sensitivities/specificities = 94%/95% and 71%/70%). Interpretation: There are cross-sectional and longitudinal differences in flortaucipir uptake between FTLD and high and low ADNC. However, optimum differentiation between FTLD and ADNC was achieved with baseline uptake rather than longitudinal rates. ANN NEUROL 2022;92:1016–1029.

AB - Objective: This study was undertaken to assess cross-sectional and longitudinal [18F]-flortaucipir positron emission tomography (PET) uptake in pathologically confirmed frontotemporal lobar degeneration (FTLD) and to compare FTLD to cases with high and low levels of Alzheimer disease (AD) neuropathologic changes (ADNC). Methods: One hundred forty-three participants who had completed at least one flortaucipir PET and had autopsy-confirmed FTLD (n = 52) or high (n = 58) or low ADNC (n = 33) based on Braak neurofibrillary tangle stages 0–IV versus V–VI were included. Flortaucipir standard uptake value ratios (SUVRs) were calculated for 9 regions of interest (ROIs): an FTLD meta-ROI, midbrain, globus pallidum, an AD meta-ROI, entorhinal, inferior temporal, orbitofrontal, precentral, and medial parietal. Linear mixed effects models were used to compare mean baseline SUVRs and annual rate of change in SUVR by group. Sensitivity and specificity to distinguish FTLD from high and low ADNC were calculated. Results: Baseline uptake in the FTLD meta-ROI, midbrain, and globus pallidus was greater in FTLD than high and low ADNC. No region showed a greater rate of flortaucipir accumulation in FTLD. Baseline uptake in the AD-related regions and orbitofrontal and precentral cortices was greater in high ADNC, and all showed greater rates of accumulation compared to FTLD. Baseline differences were superior to longitudinal rates in differentiating FTLD from high and low ADNC. A simple baseline metric of midbrain/inferior temporal ratio of flortaucipir uptake provided good to excellent differentiation between FTLD and high and low ADNC (sensitivities/specificities = 94%/95% and 71%/70%). Interpretation: There are cross-sectional and longitudinal differences in flortaucipir uptake between FTLD and high and low ADNC. However, optimum differentiation between FTLD and ADNC was achieved with baseline uptake rather than longitudinal rates. ANN NEUROL 2022;92:1016–1029.

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Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography

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