Abstract
Original language | English |
---|---|
Pages (from-to) | 335-344 |
Number of pages | 10 |
Journal | Alzheimer's and Dementia |
Volume | 16 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2020 |
Keywords
- Alzheimer's disease
- Atrophy
- Cognition
- Dementia
- Subtypes
- Tau
- Thickness
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Alzheimer's and Dementia, Vol. 16, No. 2, 01.02.2020, p. 335-344.
Research output: Contribution to journal › Article › Academic › peer-review
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, Erik
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. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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.
KW - Alzheimer's disease
KW - Atrophy
KW - Cognition
KW - Dementia
KW - Subtypes
KW - Tau
KW - Thickness
UR - http://www.scopus.com/inward/record.url?scp=85074418989&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jalz.2019.08.201
DO - https://doi.org/10.1016/j.jalz.2019.08.201
M3 - Article
C2 - 31672482
SN - 1552-5260
VL - 16
SP - 335
EP - 344
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 2
ER -