Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia

被引：138

作者：

Bergeron, David ^{[1
,2
]}

Gorno-Tempini, Maria L. ^{[3
]}

Rabinovici, Gil D. ^{[3
]}

Santos-Santos, Miguel A. ^{[3
,4
,5
]}

Seeley, William ^{[3
]}

Miller, Bruce L. ^{[3
]}

Pijnenburg, Yolande ^{[2
]}

Keulen, M. Antoinette ^{[2
]}

Groot, Colin ^{[2
]}

van Berckel, Bart N. M. ^{[6
]}

van der Flier, Wiesje M. ^{[2
]}

Scheltens, Philip ^{[2
]}

Rohrer, Jonathan D. ^{[7
]}

Warren, Jason D. ^{[7
]}

Schott, Jonathan M. ^{[7
]}

Fox, Nick C. ^{[7
]}

Sanchez-Valle, Raquel ^{[8
]}

Grau-Rivera, Oriol ^{[8
]}

Gelpi, Ellen ^{[8
,9
]}

Seelaar, Harro ^{[10
]}

Papma, Janne M. ^{[10
]}

van Swieten, John C. ^{[10
]}

Hodges, John R. ^{[11
,12
,13
]}

Leyton, Cristian E. ^{[19
]}

Piguet, Olivier ^{[11
,12
,13
]}

Rogalski, Emily J. ^{[14
,15
,16
]}

Mesulam, Marsel M. ^{[16
]}

Koric, Lejla ^{[17
]}

Nora, Kristensen ^{[17
]}

Pariente, Jeereemie ^{[18
]}

Dickerson, Bradford ^{[19
]}

Mackenzie, Ian R. ^{[20
]}

Hsiung, Ging-Yuek R. ^{[20
]}

Belliard, Serge ^{[20
]}

Irwin, David J. ^{[21
]}

Wolk, David A. ^{[22
]}

Grossman, Murray ^{[22
,23
]}

Jones, Matthew ^{[24
,25
]}

Harris, Jennifer ^{[25
]}

Mann, David ^{[26
]}

Snowden, Julie S. ^{[25
]}

Chrem-Mendez, Patricio ^{[27
]}

Calandri, Ismael L. ^{[27
]}

Amengual, Alejandra A. ^{[27
]}

Miguet-Alfonsi, Carole ^{[28
]}

Magnin, Eloi ^{[28
]}

Magnani, Giuseppe ^{[29
,30
]}

Santangelo, Roberto ^{[29
,30
]}

Deramecourt, Vincent ^{[31
]}

Pasquier, Florence ^{[31
]}

机构：

[1] Laval Univ, Interdisciplinary Clin Memory Child Jesus, Quebec City, PQ, Canada

[2] Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands

[3] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA

[4] Llobregat Hosp, Bellvitge Biomed Res Inst, Cognit & Brain Plast Grp, Barcelona, Spain

[5] UIC Barcelona, Catalan Inst Appl Neurosci, ACE Fdn, Llobregat Hosp, Barcelona, Spain

[6] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands

[7] UCL, UCL Inst Neurol, Dementia Res Ctr, London, England

[8] August Pi & Sunyer Biomed Res Inst, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain

[9] Med Univ Vienna, Inst Neurol, Vienna, Austria

[10] Erasmus Univ, Med Ctr, Dept Neurol, Alzheimer Ctr, Rotterdam, Netherlands

[11] Univ Sydney, Sch Med Sci, Brain & Mind Ctr, Sydney, NSW, Australia

[12] Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia

[13] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia

[14] Australian Res Council, Ctr Excellence Cognit & Its Disorders, Sydney, NSW, Australia

[15] Rush Univ, Neurol Sci, Chicago, IL 60612 USA

[16] Northwestern Univ, Med Sch, Cognit Neurol & Alzheimer Dis Ctr, Chicago, IL 60611 USA

[17] La Timone Hosp, Dept Neurol & Neuropsychol, Marseille, France

[18] Univ Toulouse, INSERM, Toulouse Neuroimaging Ctr, Toulouse, France

[19] Harvard Med Sch, Massachusetts Alzheimers Dis Res Ctr, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA USA

[20] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC, Canada

[21] Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA

[22] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

[23] Univ Penn, Penn Frontotemporal Degenerat Ctr, Philadelphia, PA 19104 USA

[24] Greater Manchester Neurosci Ctr, Cerebral Funct Unit, Manchester, Lancs, England

[25] Univ Manchester, Sch Community Based Med, Manchester, Lancs, England

[26] Univ Manchester, Sch Biol Sci, Div Neurosci & Expt Psychol, Manchester, Lancs, England

[27] Neurol Res Inst, Ctr Aging & Memory, Buenos Aires, DF, Argentina

[28] Univ Bourgogne Franche Comte, Reg Memory Ctr, CHRU Besancon & Integrat & Clin Neurosci Lab, Dept Neurol, Besancon, France

[29] Univ Vita Salute San Raffaele, Dept Neurol, Milan, Italy

[30] Osped San Raffaele, IRCCS, INSPE, Milan, Italy

[31] Univ Lille Nord France, INSERM, DISTALZ, U1171, Lille, France

[32] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden

[33] Skane Univ Hosp, Neuropsychiat Clin, Malmo, Sweden

[34] Univ Toronto, Sunnybrook Hlth Sci Ctr, Anat Pathol, Toronto, ON, Canada

[35] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Neurol, Toronto, ON, Canada

[36] Univ Toronto, Sunnybrook Hlth Sci Ctr, Hurvitz Brain Sci Res Program, Toronto, ON, Canada

[37] Univ Complutense Madrid, San Carlos Hlth Res Inst, San Carlos Clin Hosp, Dept Neurol & Nucl Med, Madrid, Spain

[38] Lariboisiere Fernand Widal Hosp, Dept Neurol, Memory Ctr, Paris, France

[39] Lariboisiere Fernand Widal Hosp, Dept Pathol, Paris, France

[40] Hop La Pitie Salpetriere, AP HP, Natl Reference Ctr PPA & Rare Dementias, Dept Neurol, Paris, France

[41] CEA, CNRS, Frederic Joliot Hosp Serv, ERL 9218, Orsay, Ile De France, France

[42] Univ Paris Sud, CEA, INSERM, IMIV,UMR 1023, Orsay, Ile De France, France

[43] Pitie Salpetriere Univ Hosp, Ctr Cognit & Behav Dis, Paris, France

[44] Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia

[45] Univ Melbourne, Dept Med, Melbourne, Vic, Australia

[46] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium

[47] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

[48] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[49] Univ Calif Los Angeles, Dept Neurol, Neurobehav Serv, Los Angeles, CA 90024 USA

[50] West Angeles VA Med Ctr, Neurobehav Unit, Los Angeles, CA USA

来源：

ANNALS OF NEUROLOGY | 2018年 / 84卷 / 05期

基金：

加拿大健康研究院;

关键词：

ALZHEIMER-DISEASE; FRONTOTEMPORAL PATHOLOGY; NATIONAL INSTITUTE; PET; CONSENSUS; DEMENTIA; LANGUAGE; BIOMARKERS; DIAGNOSIS; HETEROGENEITY;

D O I：

10.1002/ana.25333

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective Methods To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-beta pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) epsilon 4 status was determined using generalized estimating equation models. Results Interpretation Amyloid-beta positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-beta positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE epsilon 4 carriers were more often amyloid-beta positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-beta biomarkers in PPA patients. Ann Neurol 2018;84:737-748

引用

页码：729 / 740

页数：12

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