TY - JOUR
T1 - Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study
AU - Wolters, E. E.
AU - van de Beek, M.
AU - Ossenkoppele, R.
AU - Golla, S. S. V.
AU - Verfaillie, S. C. J.
AU - Coomans, E. M.
AU - Timmers, T.
AU - Visser, D.
AU - Tuncel, H.
AU - Barkhof, F.
AU - Boellaard, R.
AU - Windhorst, A. D.
AU - van der Flier, W. M.
AU - Scheltens, Ph.
AU - Lemstra, A. W.
AU - van Berckel, B. N. M.
N1 - Funding Information: We kindly thank all participants for their contribution. Research of Amsterdam Alzheimer Center is part of the Neurodegeneration program of Amsterdam Neuroscience. The Amsterdam Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc funds. [18F]Flortaucipir PET scans were made possible by Avid Radiopharmaceuticals Inc. Financial disclosure: This research was funded by a ZonMW Memorabel grant. FB is supported by the NIHR biomedical research centre at UCLH. Funding Information: Van der Flier received grant support from ZonMW, NWO, EU-FP7, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Stichting Dioraphte, Gieskes-Strijbis Fonds, Boehringer Ingelheim, Piramal Neuroimaging, Roche BV, Janssen Stellar, Combinostics. All funding is paid to the institution. WvdF holds the Pasman chair. Funding Information: Barkhof is editorial board member of Brain, European Radiology, Neurology®, Multiple Sclerosis Journal, and Radiology; performed consultancy and received personal compensation and honoraria from Bayer-Schering Pharma and Genzyme; received compensation (personal and to institution) and honoraria from Biogen-IDEC, TEVA, Merck-Serono, Novartis, Roche, Synthon BV, and Jansen Research; received payment for development of educational presentations from IXICO and Biogen-IDEC (to institution); is funded by a Dutch MS Society grant, EU-FP7/H2020; and is supported by the NIH Research Biomedical Research Center at University College London Hospital. Funding Information: We kindly thank all participants for their contribution. Research of Amsterdam Alzheimer Center is part of the Neurodegeneration program of Amsterdam Neuroscience. The Amsterdam Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc funds. [ 18 F]Flortaucipir PET scans were made possible by Avid Radiopharmaceuticals Inc. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose: Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [ 18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. Methods: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [ 18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BP ND) and R 1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [ 18F]flortaucipir BP ND and R 1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [ 18F]flortaucipir BP ND, R 1 and performance on ten neuropsychological tests. Results: Regional [ 18F]flortaucipir BP ND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R 1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R 1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R 1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R 1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05. Conclusion: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.
AB - Purpose: Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [ 18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. Methods: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [ 18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BP ND) and R 1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [ 18F]flortaucipir BP ND and R 1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [ 18F]flortaucipir BP ND, R 1 and performance on ten neuropsychological tests. Results: Regional [ 18F]flortaucipir BP ND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R 1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R 1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R 1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R 1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05. Conclusion: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.
KW - Cognition
KW - Dementia with Lewy bodies
KW - FDG PET
KW - Relative cerebral blood flow
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=85097206186&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nicl.2020.102504
DO - https://doi.org/10.1016/j.nicl.2020.102504
M3 - Article
C2 - 33395993
SN - 2213-1582
VL - 28
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102504
ER -