Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

Daniel Ferreira; Zuzana Nedelska; Jonathan Graff-Radford; Scott A. Przybelski; Timothy G. Lesnick; Christopher G. Schwarz; Hugo Botha; Matthew L. Senjem; Julie A. Fields; David S. Knopman; Rodolfo Savica; Tanis J. Ferman; Neill R. Graff-Radford; Val J. Lowe; Clifford R. Jack; Ronald C. Petersen; Afina W. Lemstra; Marleen van de Beek; Frederik Barkhof; Frederic Blanc; Paulo Loureiro de Sousa; Nathalie Philippi; Benjamin Cretin; Catherine Demuynck; Jakub Hort; Ketil Oppedal; Bradley F. Boeve; Dag Aarsland; Eric Westman; Kejal Kantarci

doi:https://doi.org/10.1016/j.neurobiolaging.2021.04.029

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

Daniel Ferreira, Zuzana Nedelska, Jonathan Graff-Radford, Scott A. Przybelski, Timothy G. Lesnick, Christopher G. Schwarz, Hugo Botha, Matthew L. Senjem, Julie A. Fields, David S. Knopman, Rodolfo Savica, Tanis J. Ferman, Neill R. Graff-Radford, Val J. Lowe, Clifford R. Jack, Ronald C. Petersen, Afina W. Lemstra, Marleen van de Beek, Frederik Barkhof, Frederic BlancPaulo Loureiro de Sousa, Nathalie Philippi, Benjamin Cretin, Catherine Demuynck, Jakub Hort, Ketil Oppedal, Bradley F. Boeve, Dag Aarsland, Eric Westman, Kejal Kantarci

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

16 Citations (Scopus)

Abstract

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

Original language	English
Pages (from-to)	252-261
Number of pages	10
Journal	Neurobiology of aging
Volume	105
Early online date	14 May 2021
DOIs	https://doi.org/10.1016/j.neurobiolaging.2021.04.029
Publication status	Published - 1 Sept 2021

Keywords

Cerebrovascular disease
Dementia with Lewy bodies (DLB)
Magnetic resonance imaging
Neurodegeneration
White matter hyperintensities
infarcts

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https://doi.org/10.1016/j.neurobiolaging.2021.04.029

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Ferreira, D., Nedelska, Z., Graff-Radford, J., Przybelski, S. A., Lesnick, T. G., Schwarz, C. G., Botha, H., Senjem, M. L., Fields, J. A., Knopman, D. S., Savica, R., Ferman, T. J., Graff-Radford, N. R., Lowe, V. J., Jack, C. R., Petersen, R. C., Lemstra, A. W., van de Beek, M., Barkhof, F., ... Kantarci, K. (2021). Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies. Neurobiology of aging, 105, 252-261. https://doi.org/10.1016/j.neurobiolaging.2021.04.029

@article{9091355aefa44669aff6498810533fc0,

title = "Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies",

abstract = "We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.",

keywords = "Cerebrovascular disease, Dementia with Lewy bodies (DLB), Magnetic resonance imaging, Neurodegeneration, White matter hyperintensities, infarcts",

author = "Daniel Ferreira and Zuzana Nedelska and Jonathan Graff-Radford and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Schwarz, {Christopher G.} and Hugo Botha and Senjem, {Matthew L.} and Fields, {Julie A.} and Knopman, {David S.} and Rodolfo Savica and Ferman, {Tanis J.} and Graff-Radford, {Neill R.} and Lowe, {Val J.} and Jack, {Clifford R.} and Petersen, {Ronald C.} and Lemstra, {Afina W.} and {van de Beek}, Marleen and Frederik Barkhof and Frederic Blanc and {Loureiro de Sousa}, Paulo and Nathalie Philippi and Benjamin Cretin and Catherine Demuynck and Jakub Hort and Ketil Oppedal and Boeve, {Bradley F.} and Dag Aarsland and Eric Westman and Kejal Kantarci",

note = "Funding Information: D Ferreira, SA Przybelski, TG Lesnick, AW Lemstra, Z Nedelska, CG Schwarz, H Botha, ML Senjem, JA Fields, DS Knopman, R Savica, NR Graff-Radford, RC Petersen, J Hort, K Oppedal, and E Westman report no disclosures relevant to the manuscript. J Graff-Radford receives research support from NIH. T Ferman receives funding from the Mangurian Foundation for Lewy body research and NIH. VJ Lowe serves as a consultant for AVID Radiopharmaceuticals, Bayer Schering Pharma, Eisai Inc, Philips Molecular Imaging, and Piramal Imaging and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, the NIH (NIA, NCI), and the MN Partnership for Biotechnology and Medical Genomics. CR Jack has consulted for Lily, serves on an independent data monitoring board for Roche, and as a speaker for Eisai, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. F Blanc, has served as national coordinator and principal investigator for clinical trials sponsored by Biogen, Roche, Axovant and Eisai. BF Boeve has served as an investigator for clinical trials sponsored by Biogen and Alector. He receives royalties from the publication of a book entitled Behavioral Neurology Of Dementia (Cambridge Medicine, 2017). He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program and the Little Family Foundation. D Aarsland has received research support and/or honoraria from AstraZeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and served as paid consultant for H. Lundbeck, Eisai and Evonik. K Kantarci serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc.; receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from NIH and Alzheimer's Drug Discovery Foundation. Funding Information: The authors particularly thank the patients and their family members for participating in this research. This work was supported by the National Institutes of Health ( U01- NS100620, P50-AG016574, U01-AG006786, R37-AG011378, R01-AG041851, R01-AG040042, C06-RR018898 and R01-NS080820 ), Foundation Dr. Corinne Schuler, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, the Little Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Western Norway Regional Health Authority, the Swedish Foundation for Strategic Research (SSF), the Swedish Research Council (VR), Karolinska Institutet travel grants, Center for Innovative Medicine (CIMED), the Foundation for Geriatric Diseases at Karolinska Institutet, the NIHR biomedical research centre at UCLH, and the Projet Hospitalier de Recherche Clinique ( PHRC, IDCRB 2012-A00992-41 ) and fondation Universit{\'e} de Strasbourg. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Funding Information: The authors particularly thank the patients and their family members for participating in this research. This work was supported by the National Institutes of Health (U01- NS100620, P50-AG016574, U01-AG006786, R37-AG011378, R01-AG041851, R01-AG040042, C06-RR018898 and R01-NS080820), Foundation Dr. Corinne Schuler, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, the Little Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Western Norway Regional Health Authority, the Swedish Foundation for Strategic Research (SSF), the Swedish Research Council (VR), Karolinska Institutet travel grants, Center for Innovative Medicine (CIMED), the Foundation for Geriatric Diseases at Karolinska Institutet, the NIHR biomedical research centre at UCLH, and the Projet Hospitalier de Recherche Clinique (PHRC, IDCRB 2012-A00992-41) and fondation Universit? de Strasbourg. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = sep,

day = "1",

doi = "https://doi.org/10.1016/j.neurobiolaging.2021.04.029",

language = "English",

volume = "105",

pages = "252--261",

journal = "Neurobiology of aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

Ferreira, D, Nedelska, Z, Graff-Radford, J, Przybelski, SA, Lesnick, TG, Schwarz, CG, Botha, H, Senjem, ML, Fields, JA, Knopman, DS, Savica, R, Ferman, TJ, Graff-Radford, NR, Lowe, VJ, Jack, CR, Petersen, RC, Lemstra, AW, van de Beek, M, Barkhof, F, Blanc, F, Loureiro de Sousa, P, Philippi, N, Cretin, B, Demuynck, C, Hort, J, Oppedal, K, Boeve, BF, Aarsland, D, Westman, E & Kantarci, K 2021, 'Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies', Neurobiology of aging, vol. 105, pp. 252-261. https://doi.org/10.1016/j.neurobiolaging.2021.04.029

TY - JOUR

T1 - Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

AU - Ferreira, Daniel

AU - Nedelska, Zuzana

AU - Graff-Radford, Jonathan

AU - Przybelski, Scott A.

AU - Lesnick, Timothy G.

AU - Schwarz, Christopher G.

AU - Botha, Hugo

AU - Senjem, Matthew L.

AU - Fields, Julie A.

AU - Knopman, David S.

AU - Savica, Rodolfo

AU - Ferman, Tanis J.

AU - Graff-Radford, Neill R.

AU - Lowe, Val J.

AU - Jack, Clifford R.

AU - Petersen, Ronald C.

AU - Lemstra, Afina W.

AU - van de Beek, Marleen

AU - Barkhof, Frederik

AU - Blanc, Frederic

AU - Loureiro de Sousa, Paulo

AU - Philippi, Nathalie

AU - Cretin, Benjamin

AU - Demuynck, Catherine

AU - Hort, Jakub

AU - Oppedal, Ketil

AU - Boeve, Bradley F.

AU - Aarsland, Dag

AU - Westman, Eric

AU - Kantarci, Kejal

N1 - Funding Information: D Ferreira, SA Przybelski, TG Lesnick, AW Lemstra, Z Nedelska, CG Schwarz, H Botha, ML Senjem, JA Fields, DS Knopman, R Savica, NR Graff-Radford, RC Petersen, J Hort, K Oppedal, and E Westman report no disclosures relevant to the manuscript. J Graff-Radford receives research support from NIH. T Ferman receives funding from the Mangurian Foundation for Lewy body research and NIH. VJ Lowe serves as a consultant for AVID Radiopharmaceuticals, Bayer Schering Pharma, Eisai Inc, Philips Molecular Imaging, and Piramal Imaging and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, the NIH (NIA, NCI), and the MN Partnership for Biotechnology and Medical Genomics. CR Jack has consulted for Lily, serves on an independent data monitoring board for Roche, and as a speaker for Eisai, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. F Blanc, has served as national coordinator and principal investigator for clinical trials sponsored by Biogen, Roche, Axovant and Eisai. BF Boeve has served as an investigator for clinical trials sponsored by Biogen and Alector. He receives royalties from the publication of a book entitled Behavioral Neurology Of Dementia (Cambridge Medicine, 2017). He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program and the Little Family Foundation. D Aarsland has received research support and/or honoraria from AstraZeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and served as paid consultant for H. Lundbeck, Eisai and Evonik. K Kantarci serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc.; receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from NIH and Alzheimer's Drug Discovery Foundation. Funding Information: The authors particularly thank the patients and their family members for participating in this research. This work was supported by the National Institutes of Health ( U01- NS100620, P50-AG016574, U01-AG006786, R37-AG011378, R01-AG041851, R01-AG040042, C06-RR018898 and R01-NS080820 ), Foundation Dr. Corinne Schuler, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, the Little Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Western Norway Regional Health Authority, the Swedish Foundation for Strategic Research (SSF), the Swedish Research Council (VR), Karolinska Institutet travel grants, Center for Innovative Medicine (CIMED), the Foundation for Geriatric Diseases at Karolinska Institutet, the NIHR biomedical research centre at UCLH, and the Projet Hospitalier de Recherche Clinique ( PHRC, IDCRB 2012-A00992-41 ) and fondation Université de Strasbourg. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Funding Information: The authors particularly thank the patients and their family members for participating in this research. This work was supported by the National Institutes of Health (U01- NS100620, P50-AG016574, U01-AG006786, R37-AG011378, R01-AG041851, R01-AG040042, C06-RR018898 and R01-NS080820), Foundation Dr. Corinne Schuler, the Mangurian Foundation for Lewy Body Research, the Elsie and Marvin Dekelboum Family Foundation, the Little Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the Western Norway Regional Health Authority, the Swedish Foundation for Strategic Research (SSF), the Swedish Research Council (VR), Karolinska Institutet travel grants, Center for Innovative Medicine (CIMED), the Foundation for Geriatric Diseases at Karolinska Institutet, the NIHR biomedical research centre at UCLH, and the Projet Hospitalier de Recherche Clinique (PHRC, IDCRB 2012-A00992-41) and fondation Universit? de Strasbourg. The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: © 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

AB - We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

KW - Cerebrovascular disease

KW - Dementia with Lewy bodies (DLB)

KW - Magnetic resonance imaging

KW - Neurodegeneration

KW - White matter hyperintensities

KW - infarcts

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85107763909&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/34130107

U2 - https://doi.org/10.1016/j.neurobiolaging.2021.04.029

DO - https://doi.org/10.1016/j.neurobiolaging.2021.04.029

M3 - Article

C2 - 34130107

SN - 0197-4580

VL - 105

SP - 252

EP - 261

JO - Neurobiology of aging

JF - Neurobiology of aging

ER -

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

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Keywords

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