Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

Rik Ossenkoppele; Chul Hyoung Lyoo; Carole H. Sudre; Danielle van Westen; Hanna Cho; Young Hoon Ryu; Jae Yong Choi; Ruben Smith; Olof Strandberg; Sebastian Palmqvist; Eric Westman; Richard Tsai; Joel Kramer; Adam L. Boxer; Maria L. Gorno-Tempini; Renaud La Joie; Bruce L. Miller; Gil D. Rabinovici; Oskar Hansson

doi:10.1016/j.jalz.2019.08.201

Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

Rik Ossenkoppele, Chul Hyoung Lyoo, Carole H. Sudre, Danielle van Westen, Hanna Cho, Young Hoon Ryu, Jae Yong Choi, Ruben Smith, Olof Strandberg, Sebastian Palmqvist, Eric Westman, Richard Tsai, Joel Kramer, Adam L. Boxer, Maria L. Gorno-Tempini, Renaud La Joie, Bruce L. Miller, Gil D. Rabinovici, Oskar Hansson

Department of Neurology

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

44 Citations (Scopus)

Abstract

Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [¹⁸F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

Original language	English
Pages (from-to)	335-344
Number of pages	10
Journal	Alzheimer's and Dementia
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.jalz.2019.08.201
Publication status	Published - 2020 Feb 1

Bibliographical note

Funding Information:
Work at Lund University was supported by the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg foundation, the Knut and Alice Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skfine University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of 18F-flutemetamol injection were sponsored by GE Healthcare. Work at UCSF was supported by National Institute on Aging grants (R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, and U54-NS092089), the Alzheimer's Association (AARF-16-443577), Tau Consortium, and the Michael J Fox foundation. Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP, 2015R1C1A2A01054507) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2017R1A2B2006694). C.H.S. is funded by the Alzheimer's Society (AS-JF-17-011). For UCSF and the BioFINDER study, the precursor of [18F]flortaucipir was provided by AVID radiopharmaceuticals. Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983, the Tau Research Consortium, the Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, and the Alzheimer's Association. He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceu- ticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest.

Funding Information:
Work at Lund University was supported by the European Research Council , the Swedish Research Council , the Marianne and Marcus Wallenberg foundation , the Knut and Alice Wallenberg foundation , the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University , the Swedish Brain Foundation , the Swedish Alzheimer Foundation , The Parkinson Foundation of Sweden, The Parkinson Research Foundation , the Skåne University Hospital Foundation , and the Swedish federal government under the ALF agreement. Doses of 18 F-flutemetamol injection were sponsored by GE Healthcare . Work at UCSF was supported by National Institute on Aging grants ( R01-AG045611 , P50-AG023501 , P01-AG19724 , R01-AG038791 , and U54-NS092089 ), the Alzheimer's Association ( AARF-16-443577 ), Tau Consortium, and the Michael J Fox foundation . Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MSIP , 2015R1C1A2A01054507 ) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning ( 2017R1A2B2006694 ). C.H.S. is funded by the Alzheimer's Society ( AS-JF-17-011 ). For UCSF and the BioFINDER study, the precursor of [ 18 F]flortaucipir was provided by AVID radiopharmaceuticals.

Funding Information:
Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare , Biogen , AVID Radiopharmaceuticals , Fujirebio , and Euroimmun . In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089 , R01AG031278 , R01AG038791 , R01AG032306 , R01AG022983 , the Tau Research Consortium , the Bluefield Project to Cure Frontotemporal Dementia , Corticobasal Degeneration Solutions , and the Alzheimer's Association . He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest.

Publisher Copyright:
© 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

All Science Journal Classification (ASJC) codes

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jalz.2019.08.201

Cite this

Ossenkoppele, R., Lyoo, C. H., Sudre, C. H., van Westen, D., Cho, H., Ryu, Y. H., Choi, J. Y., Smith, R., Strandberg, O., Palmqvist, S., Westman, E., Tsai, R., Kramer, J., Boxer, A. L., Gorno-Tempini, M. L., La Joie, R., Miller, B. L., Rabinovici, G. D., & Hansson, O. (2020). Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease. Alzheimer's and Dementia, 16(2), 335-344. https://doi.org/10.1016/j.jalz.2019.08.201

@article{cca8a88c317541df8903c66537ce84d1,

title = "Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease",

abstract = "Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.",

author = "Rik Ossenkoppele and Lyoo, {Chul Hyoung} and Sudre, {Carole H.} and {van Westen}, Danielle and Hanna Cho and Ryu, {Young Hoon} and Choi, {Jae Yong} and Ruben Smith and Olof Strandberg and Sebastian Palmqvist and Eric Westman and Richard Tsai and Joel Kramer and Boxer, {Adam L.} and Gorno-Tempini, {Maria L.} and {La Joie}, Renaud and Miller, {Bruce L.} and Rabinovici, {Gil D.} and Oskar Hansson",

note = "Funding Information: Work at Lund University was supported by the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg foundation, the Knut and Alice Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skfine University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of 18F-flutemetamol injection were sponsored by GE Healthcare. Work at UCSF was supported by National Institute on Aging grants (R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, and U54-NS092089), the Alzheimer's Association (AARF-16-443577), Tau Consortium, and the Michael J Fox foundation. Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP, 2015R1C1A2A01054507) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2017R1A2B2006694). C.H.S. is funded by the Alzheimer's Society (AS-JF-17-011). For UCSF and the BioFINDER study, the precursor of [18F]flortaucipir was provided by AVID radiopharmaceuticals. Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983, the Tau Research Consortium, the Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, and the Alzheimer's Association. He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceu- ticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest. Funding Information: Work at Lund University was supported by the European Research Council , the Swedish Research Council , the Marianne and Marcus Wallenberg foundation , the Knut and Alice Wallenberg foundation , the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University , the Swedish Brain Foundation , the Swedish Alzheimer Foundation , The Parkinson Foundation of Sweden, The Parkinson Research Foundation , the Sk{\aa}ne University Hospital Foundation , and the Swedish federal government under the ALF agreement. Doses of 18 F-flutemetamol injection were sponsored by GE Healthcare . Work at UCSF was supported by National Institute on Aging grants ( R01-AG045611 , P50-AG023501 , P01-AG19724 , R01-AG038791 , and U54-NS092089 ), the Alzheimer's Association ( AARF-16-443577 ), Tau Consortium, and the Michael J Fox foundation . Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MSIP , 2015R1C1A2A01054507 ) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning ( 2017R1A2B2006694 ). C.H.S. is funded by the Alzheimer's Society ( AS-JF-17-011 ). For UCSF and the BioFINDER study, the precursor of [ 18 F]flortaucipir was provided by AVID radiopharmaceuticals. Funding Information: Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare , Biogen , AVID Radiopharmaceuticals , Fujirebio , and Euroimmun . In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089 , R01AG031278 , R01AG038791 , R01AG032306 , R01AG022983 , the Tau Research Consortium , the Bluefield Project to Cure Frontotemporal Dementia , Corticobasal Degeneration Solutions , and the Alzheimer's Association . He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.",

year = "2020",

month = feb,

day = "1",

doi = "10.1016/j.jalz.2019.08.201",

language = "English",

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journal = "Alzheimer's and Dementia",

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Ossenkoppele, R, Lyoo, CH, Sudre, CH, van Westen, D, Cho, H, Ryu, YH, Choi, JY, Smith, R, Strandberg, O, Palmqvist, S, Westman, E, Tsai, R, Kramer, J, Boxer, AL, Gorno-Tempini, ML, La Joie, R, Miller, BL, Rabinovici, GD & Hansson, O 2020, 'Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease', Alzheimer's and Dementia, vol. 16, no. 2, pp. 335-344. https://doi.org/10.1016/j.jalz.2019.08.201

TY - JOUR

T1 - Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

AU - Ossenkoppele, Rik

AU - Lyoo, Chul Hyoung

AU - Sudre, Carole H.

AU - van Westen, Danielle

AU - Cho, Hanna

AU - Ryu, Young Hoon

AU - Choi, Jae Yong

AU - Smith, Ruben

AU - Strandberg, Olof

AU - Palmqvist, Sebastian

AU - Westman, Eric

AU - Tsai, Richard

AU - Kramer, Joel

AU - Boxer, Adam L.

AU - Gorno-Tempini, Maria L.

AU - La Joie, Renaud

AU - Miller, Bruce L.

AU - Rabinovici, Gil D.

AU - Hansson, Oskar

N1 - Funding Information: Work at Lund University was supported by the European Research Council, the Swedish Research Council, the Marianne and Marcus Wallenberg foundation, the Knut and Alice Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, The Parkinson Foundation of Sweden, The Parkinson Research Foundation, the Skfine University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of 18F-flutemetamol injection were sponsored by GE Healthcare. Work at UCSF was supported by National Institute on Aging grants (R01-AG045611, P50-AG023501, P01-AG19724, R01-AG038791, and U54-NS092089), the Alzheimer's Association (AARF-16-443577), Tau Consortium, and the Michael J Fox foundation. Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP, 2015R1C1A2A01054507) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning (2017R1A2B2006694). C.H.S. is funded by the Alzheimer's Society (AS-JF-17-011). For UCSF and the BioFINDER study, the precursor of [18F]flortaucipir was provided by AVID radiopharmaceuticals. Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983, the Tau Research Consortium, the Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, and the Alzheimer's Association. He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceu- ticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest. Funding Information: Work at Lund University was supported by the European Research Council , the Swedish Research Council , the Marianne and Marcus Wallenberg foundation , the Knut and Alice Wallenberg foundation , the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University , the Swedish Brain Foundation , the Swedish Alzheimer Foundation , The Parkinson Foundation of Sweden, The Parkinson Research Foundation , the Skåne University Hospital Foundation , and the Swedish federal government under the ALF agreement. Doses of 18 F-flutemetamol injection were sponsored by GE Healthcare . Work at UCSF was supported by National Institute on Aging grants ( R01-AG045611 , P50-AG023501 , P01-AG19724 , R01-AG038791 , and U54-NS092089 ), the Alzheimer's Association ( AARF-16-443577 ), Tau Consortium, and the Michael J Fox foundation . Work at Gangnam Severance Hospital was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MSIP , 2015R1C1A2A01054507 ) and Basic Science Research Program through the NRF funded by the Ministry of Science, ICT & Future Planning ( 2017R1A2B2006694 ). C.H.S. is funded by the Alzheimer's Society ( AS-JF-17-011 ). For UCSF and the BioFINDER study, the precursor of [ 18 F]flortaucipir was provided by AVID radiopharmaceuticals. Funding Information: Disclosures: O.H. has acquired research support (for the institution) from Roche, GE Healthcare , Biogen , AVID Radiopharmaceuticals , Fujirebio , and Euroimmun . In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche, and Fujirebio. A.L.B. receives research support from NIH U54NS092089 , R01AG031278 , R01AG038791 , R01AG032306 , R01AG022983 , the Tau Research Consortium , the Bluefield Project to Cure Frontotemporal Dementia , Corticobasal Degeneration Solutions , and the Alzheimer's Association . He has served as a consultant for Abbvie, Amgen, Celgene, Ionis, Janssen, Merck, UCB, and Toyama and received research support from Avid, Biogen, BMS, C2N, Cortice, Forum, Genentech, Janssen, Pfizer, Eli Lilly, Roche, and TauRx, He holds stock options in Aeton, Alector, and Delos. G.D.R. receives research support from Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, and Piramal. He has received speaking honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche. B.L.M. is the Medical Director for John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation. The other authors report no conflicts of interest. Publisher Copyright: © 2019 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

AB - Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.

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U2 - 10.1016/j.jalz.2019.08.201

DO - 10.1016/j.jalz.2019.08.201

M3 - Article

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AN - SCOPUS:85074418989

SN - 1552-5260

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JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 2

ER -

Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease

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