Multicenter Study

. 2020 Dec 15;95(24):e3257-e3268.

doi: 10.1212/WNL.0000000000010943. Epub 2020 Sep 28.

β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies

Daniel Ferreira¹, Scott A Przybelski¹, Timothy G Lesnick¹, Afina W Lemstra¹, Elisabet Londos¹, Frederic Blanc¹, Zuzana Nedelska¹, Christopher G Schwarz¹, Jonathan Graff-Radford¹, Matthew L Senjem¹, Julie A Fields¹, David S Knopman¹, Rodolfo Savica¹, Tanis J Ferman¹, Neill R Graff-Radford¹, Val J Lowe¹, Clifford R Jack Jr¹, Ronald C Petersen¹, Brit Mollenhauer¹, Sara Garcia-Ptacek¹, Carla Abdelnour¹, Jakub Hort¹, Laura Bonanni¹, Ketil Oppedal¹, Milica G Kramberger¹, Bradley F Boeve¹, Dag Aarsland¹, Eric Westman¹, Kejal Kantarci²

Affiliations

¹ From the Division of Clinical Geriatrics (D.F., S.G.-P., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., Z.N., C.G.S., M.L.S., V.J.L., C.R.J., K.K.), Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Department of Neurology and Alzheimer Center (A.W.L.), VU University Medical Center, Amsterdam, the Netherlands; Clinical Memory Research Unit (E.L.), Department of Clinical Sciences, Lund University, Malmö, Sweden; Day Hospital of Geriatrics (F.B.), Memory Resource and Research Centre (CM2R) of Strasbourg; Department of Geriatrics (F.B.), Hopitaux Universitaires de Strasbourg; University of Strasbourg and French National Centre for Scientific Research (CNRS) (F.B.), ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg (FMTS), Team Imagerie Multimodale Integrative en Sante (IMIS)/ICONE, Strasbourg, France; Department of Neurology (Z.N., J.H.), Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Paracelsus-Elena-Klinik (B.M.), Kassel; and University Medical Center (B.M.), Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany; Fundació ACE (C.A.), Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain; International Clinical Research Center (J.H.), St. Anne's University Hospital Brno, Czech Republic; Department of Neuroscience Imaging and Clinical Sciences and CESI (L.B.), University G d'Annunzio of Chieti-Pescara, Chieti, Italy; Centre for Age-Related Medicine (K.O., D.A.), Stavanger University Hospital; Stavanger Medical Imaging Laboratory (SMIL) (K.O.), Department of Radiology, Stavanger University Hospital; Department of Electrical Engineering and Computer Science (K.O.), University of Stavanger, Norway; Department of Neurology (M.G.K.), University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Slovenia; Institute of Psychiatry, Psychology and Neuroscience (D.A.) and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
² From the Division of Clinical Geriatrics (D.F., S.G.-P., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., Z.N., C.G.S., M.L.S., V.J.L., C.R.J., K.K.), Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Department of Neurology and Alzheimer Center (A.W.L.), VU University Medical Center, Amsterdam, the Netherlands; Clinical Memory Research Unit (E.L.), Department of Clinical Sciences, Lund University, Malmö, Sweden; Day Hospital of Geriatrics (F.B.), Memory Resource and Research Centre (CM2R) of Strasbourg; Department of Geriatrics (F.B.), Hopitaux Universitaires de Strasbourg; University of Strasbourg and French National Centre for Scientific Research (CNRS) (F.B.), ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg (FMTS), Team Imagerie Multimodale Integrative en Sante (IMIS)/ICONE, Strasbourg, France; Department of Neurology (Z.N., J.H.), Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Paracelsus-Elena-Klinik (B.M.), Kassel; and University Medical Center (B.M.), Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany; Fundació ACE (C.A.), Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain; International Clinical Research Center (J.H.), St. Anne's University Hospital Brno, Czech Republic; Department of Neuroscience Imaging and Clinical Sciences and CESI (L.B.), University G d'Annunzio of Chieti-Pescara, Chieti, Italy; Centre for Age-Related Medicine (K.O., D.A.), Stavanger University Hospital; Stavanger Medical Imaging Laboratory (SMIL) (K.O.), Department of Radiology, Stavanger University Hospital; Department of Electrical Engineering and Computer Science (K.O.), University of Stavanger, Norway; Department of Neurology (M.G.K.), University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Slovenia; Institute of Psychiatry, Psychology and Neuroscience (D.A.) and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. kantarci.kejal@mayo.edu.

PMID: 32989106
PMCID: PMC7836666
DOI: 10.1212/WNL.0000000000010943

Multicenter Study

β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies

Daniel Ferreira et al. Neurology. 2020.

. 2020 Dec 15;95(24):e3257-e3268.

doi: 10.1212/WNL.0000000000010943. Epub 2020 Sep 28.

Authors

Affiliations

¹ From the Division of Clinical Geriatrics (D.F., S.G.-P., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., Z.N., C.G.S., M.L.S., V.J.L., C.R.J., K.K.), Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Department of Neurology and Alzheimer Center (A.W.L.), VU University Medical Center, Amsterdam, the Netherlands; Clinical Memory Research Unit (E.L.), Department of Clinical Sciences, Lund University, Malmö, Sweden; Day Hospital of Geriatrics (F.B.), Memory Resource and Research Centre (CM2R) of Strasbourg; Department of Geriatrics (F.B.), Hopitaux Universitaires de Strasbourg; University of Strasbourg and French National Centre for Scientific Research (CNRS) (F.B.), ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg (FMTS), Team Imagerie Multimodale Integrative en Sante (IMIS)/ICONE, Strasbourg, France; Department of Neurology (Z.N., J.H.), Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Paracelsus-Elena-Klinik (B.M.), Kassel; and University Medical Center (B.M.), Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany; Fundació ACE (C.A.), Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain; International Clinical Research Center (J.H.), St. Anne's University Hospital Brno, Czech Republic; Department of Neuroscience Imaging and Clinical Sciences and CESI (L.B.), University G d'Annunzio of Chieti-Pescara, Chieti, Italy; Centre for Age-Related Medicine (K.O., D.A.), Stavanger University Hospital; Stavanger Medical Imaging Laboratory (SMIL) (K.O.), Department of Radiology, Stavanger University Hospital; Department of Electrical Engineering and Computer Science (K.O.), University of Stavanger, Norway; Department of Neurology (M.G.K.), University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Slovenia; Institute of Psychiatry, Psychology and Neuroscience (D.A.) and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
² From the Division of Clinical Geriatrics (D.F., S.G.-P., E.W.), Center for Alzheimer's Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Departments of Radiology (D.F., Z.N., C.G.S., M.L.S., V.J.L., C.R.J., K.K.), Health Sciences (S.A.P., T.G.L.), Neurology (J.G.-R., D.S.K., R.S., R.C.P., B.F.B.), Information Technology (M.L.S.), and Psychiatry and Psychology (J.A.F.), Mayo Clinic, Rochester, MN; Department of Neurology and Alzheimer Center (A.W.L.), VU University Medical Center, Amsterdam, the Netherlands; Clinical Memory Research Unit (E.L.), Department of Clinical Sciences, Lund University, Malmö, Sweden; Day Hospital of Geriatrics (F.B.), Memory Resource and Research Centre (CM2R) of Strasbourg; Department of Geriatrics (F.B.), Hopitaux Universitaires de Strasbourg; University of Strasbourg and French National Centre for Scientific Research (CNRS) (F.B.), ICube Laboratory and Federation de Medecine Translationnelle de Strasbourg (FMTS), Team Imagerie Multimodale Integrative en Sante (IMIS)/ICONE, Strasbourg, France; Department of Neurology (Z.N., J.H.), Charles University, 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic; Departments of Psychiatry and Psychology (T.J.F.) and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Paracelsus-Elena-Klinik (B.M.), Kassel; and University Medical Center (B.M.), Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany; Fundació ACE (C.A.), Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain; International Clinical Research Center (J.H.), St. Anne's University Hospital Brno, Czech Republic; Department of Neuroscience Imaging and Clinical Sciences and CESI (L.B.), University G d'Annunzio of Chieti-Pescara, Chieti, Italy; Centre for Age-Related Medicine (K.O., D.A.), Stavanger University Hospital; Stavanger Medical Imaging Laboratory (SMIL) (K.O.), Department of Radiology, Stavanger University Hospital; Department of Electrical Engineering and Computer Science (K.O.), University of Stavanger, Norway; Department of Neurology (M.G.K.), University Medical Centre Ljubljana, Medical Faculty, University of Ljubljana, Slovenia; Institute of Psychiatry, Psychology and Neuroscience (D.A.) and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. kantarci.kejal@mayo.edu.

PMID: 32989106
PMCID: PMC7836666
DOI: 10.1212/WNL.0000000000010943

Abstract

Objective: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype.

Methods: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid_1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+.

Results: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype.

Conclusions: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB.

Classification of evidence: This study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.

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Figures

**Figure 1. Percentage of the AT groups (A) in the whole sample and (B) by center and (C) deviation from cut points**
Center A = Fundació ACE Barcelona (Spain); Center B = University G d'Annunzio of Chieti-Pescara (Italy); Center C = Center for Age-Related Medicine, Stavanger University Hospital, Stavanger (Norway); Center D = Memory Clinic, Karolinska University Hospital, Huddinge (Sweden); Center E = University of Ljubljana (Slovenia); Center F = Clinical Memory Research Unit, Lund University (Sweden); Center G = Mayo Clinic at Rochester, MN (United States); Center H = Paracelsus-Elena-Klinik, Kassel (Germany); Center I = Motol University Hospital, Prague (Czech Republic); Center J = Neuropsychology Unit and Geriatric Day Hospital, University Hospital of Strasbourg, Strasbourg (France); Center K = VUMC Amsterdam (the Netherlands). (C) AT groups with the deviation of each individual from cut points (zero value), specific to center and biomarker modality (CSF or PET). A = β-amyloid; T = tau; + = abnormal values; − = normal values.

**Figure 2. Predicted percentages of AT groups by age**
A = β-amyloid; T = tau; + = abnormal values; − = normal values.

**Figure 3. Percentage of AT groups by sex and *APOE* ε4 status**
A = β-amyloid; T = tau; + = abnormal values; − = normal values.

See this image and copyright information in PMC

Comment in

Alzheimer disease biomarker profiles in dementia with Lewy bodies: Does A plus T spell D-L-B?
Koyama AK, Irwin DJ. Koyama AK, et al. Neurology. 2020 Dec 15;95(24):1076-1077. doi: 10.1212/WNL.0000000000010958. Epub 2020 Sep 28. Neurology. 2020. PMID: 32989112 No abstract available.

References

1. Irwin DJ, Grossman M, Weintraub D, et al. Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol 2017;16:55–65. - PMC - PubMed
1. Schoonenboom NS, Reesink FE, Verwey NA, et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 2012;78:47–54. - PubMed
1. Sarro L, Senjem ML, Lundt ES, et al. Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies. Brain 2016;139:2740–2750. - PMC - PubMed
1. Gomperts SN, Locascio JJ, Marquie M, et al. Brain amyloid and cognition in Lewy body diseases. Mov Disord 2012;27:965–973. - PMC - PubMed
1. Lee SH, Cho H, Choi JY, et al. Distinct patterns of amyloid-dependent tau accumulation in Lewy body diseases. Mov Disord 2018;33:262–272. - PubMed

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β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies

Affiliations

β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous