Prevalence of amyloid-beta pathology in distinct variants of primary progressive aphasia
Por:
Bergeron, D, Gorno-Tempini, ML, Rabinovici, GD, Santos-Santos, MA, Seeley, W, Miller, BL, Pijnenburg, Y, Keulen, MA, Groot, C, Berckel, BNM, Flier, WMD, Scheltens, P, Rohrer, JD, Warren, JD, Schott, JM, Fox, NC, Sanchez-Valle, R, Grau-Rivera, O, Gelpi, E, Seelaar, H, Papma, JM, Swieten, JC, Hodges, JR, Leyton, CE, Piguet, O, Rogalski, EJ, Mesulam, MM, Koric, L, Nora, K, Pariente, J, Dickerson, B, Mackenzie, IR, Hsiung, GYR, Belliard, S, Irwin, DJ, Wolk, DA, Grossman, M, Jones, M, Harris, J, Mann, D, Snowden, JS, Chrem-Mendez, P, Calandri, IL, Amengual, AA, Miguet-Alfonsi, C, Magnin, E, Magnani, G, Santangelo, R, Deramecourt, V, Pasquier, F, Mattsson, N, Nilsson, C, Hansson, O, Keith, J, Masellis, M, Black, SE, Matias-Guiu, JA, Cabrera-Martin, MN, Paquet, C, Dumurgier, J, Teichmann, M, Sarazin, M, Bottlaender, M, Dubois, B, Rowe, CC, Villemagne, VL, Vandenberghe, R, Granadillo, E, Teng, E, Mendez, M, Meyer, PT, Frings, L, Lleo, A, Blesa, R, Fortea, J, Seo, SW, Diehl-Schmid, J, Grimmer, T, Frederiksen, KS, Sanchez-Juan, P, Chetelat, G, Jansen, W, Bouchard, RW, Laforce, RJ, Visser, PJ, Ossenkoppele, R
Publicada:
1 nov 2018
Resumen:
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
Filiaciones:
Bergeron, D:
Laval Univ, Interdisciplinary Clin Memory Child Jesus, Quebec City, PQ, Canada
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Gorno-Tempini, ML:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA
Rabinovici, GD:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA
Santos-Santos, MA:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA
Llobregat Hosp, Bellvitge Biomed Res Inst, Cognit & Brain Plast Grp, Barcelona, Spain
UIC Barcelona, Catalan Inst Appl Neurosci, ACE Fdn, Llobregat Hosp, Barcelona, Spain
Seeley, W:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA
Miller, BL:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA
Pijnenburg, Y:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Keulen, MA:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Groot, C:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Berckel, BNM:
Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands
Flier, WMD:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Scheltens, P:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Rohrer, JD:
UCL, UCL Inst Neurol, Dementia Res Ctr, London, England
Warren, JD:
UCL, UCL Inst Neurol, Dementia Res Ctr, London, England
Schott, JM:
UCL, UCL Inst Neurol, Dementia Res Ctr, London, England
Fox, NC:
UCL, UCL Inst Neurol, Dementia Res Ctr, London, England
Sanchez-Valle, R:
August Pi & Sunyer Biomed Res Inst, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Grau-Rivera, O:
August Pi & Sunyer Biomed Res Inst, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Gelpi, E:
August Pi & Sunyer Biomed Res Inst, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Med Univ Vienna, Inst Neurol, Vienna, Austria
Seelaar, H:
Erasmus Univ, Med Ctr, Dept Neurol, Alzheimer Ctr, Rotterdam, Netherlands
Papma, JM:
Erasmus Univ, Med Ctr, Dept Neurol, Alzheimer Ctr, Rotterdam, Netherlands
Swieten, JC:
Erasmus Univ, Med Ctr, Dept Neurol, Alzheimer Ctr, Rotterdam, Netherlands
Hodges, JR:
Univ Sydney, Sch Med Sci, Brain & Mind Ctr, Sydney, NSW, Australia
Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia
Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
Leyton, CE:
Harvard Med Sch, Massachusetts Alzheimers Dis Res Ctr, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA USA
Piguet, O:
Univ Sydney, Sch Med Sci, Brain & Mind Ctr, Sydney, NSW, Australia
Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia
Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
Rogalski, EJ:
Australian Res Council, Ctr Excellence Cognit & Its Disorders, Sydney, NSW, Australia
Rush Univ, Neurol Sci, Chicago, IL 60612 USA
Northwestern Univ, Med Sch, Cognit Neurol & Alzheimer Dis Ctr, Chicago, IL 60611 USA
Mesulam, MM:
Northwestern Univ, Med Sch, Cognit Neurol & Alzheimer Dis Ctr, Chicago, IL 60611 USA
Koric, L:
La Timone Hosp, Dept Neurol & Neuropsychol, Marseille, France
Nora, K:
La Timone Hosp, Dept Neurol & Neuropsychol, Marseille, France
Pariente, J:
Univ Toulouse, INSERM, Toulouse Neuroimaging Ctr, Toulouse, France
Dickerson, B:
Harvard Med Sch, Massachusetts Alzheimers Dis Res Ctr, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA USA
Mackenzie, IR:
Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC, Canada
Hsiung, GYR:
Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC, Canada
Belliard, S:
Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC, Canada
Irwin, DJ:
Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
Wolk, DA:
Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
Grossman, M:
Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
Univ Penn, Penn Frontotemporal Degenerat Ctr, Philadelphia, PA 19104 USA
Jones, M:
Greater Manchester Neurosci Ctr, Cerebral Funct Unit, Manchester, Lancs, England
Univ Manchester, Sch Community Based Med, Manchester, Lancs, England
Harris, J:
Univ Manchester, Sch Community Based Med, Manchester, Lancs, England
Mann, D:
Univ Manchester, Sch Biol Sci, Div Neurosci & Expt Psychol, Manchester, Lancs, England
Snowden, JS:
Univ Manchester, Sch Community Based Med, Manchester, Lancs, England
Chrem-Mendez, P:
Neurol Res Inst, Ctr Aging & Memory, Buenos Aires, DF, Argentina
Calandri, IL:
Neurol Res Inst, Ctr Aging & Memory, Buenos Aires, DF, Argentina
Amengual, AA:
Neurol Res Inst, Ctr Aging & Memory, Buenos Aires, DF, Argentina
Miguet-Alfonsi, C:
Univ Bourgogne Franche Comte, Reg Memory Ctr, CHRU Besancon & Integrat & Clin Neurosci Lab, Dept Neurol, Besancon, France
Magnin, E:
Univ Bourgogne Franche Comte, Reg Memory Ctr, CHRU Besancon & Integrat & Clin Neurosci Lab, Dept Neurol, Besancon, France
Magnani, G:
Univ Vita Salute San Raffaele, Dept Neurol, Milan, Italy
Osped San Raffaele, IRCCS, INSPE, Milan, Italy
Santangelo, R:
Univ Vita Salute San Raffaele, Dept Neurol, Milan, Italy
Osped San Raffaele, IRCCS, INSPE, Milan, Italy
Deramecourt, V:
Univ Lille Nord France, INSERM, DISTALZ, U1171, Lille, France
Pasquier, F:
Univ Lille Nord France, INSERM, DISTALZ, U1171, Lille, France
Mattsson, N:
Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
Nilsson, C:
Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
Hansson, O:
Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Neuropsychiat Clin, Malmo, Sweden
Keith, J:
Univ Toronto, Sunnybrook Hlth Sci Ctr, Anat Pathol, Toronto, ON, Canada
Masellis, M:
Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Neurol, Toronto, ON, Canada
Univ Toronto, Sunnybrook Hlth Sci Ctr, Hurvitz Brain Sci Res Program, Toronto, ON, Canada
Black, SE:
Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Neurol, Toronto, ON, Canada
Univ Toronto, Sunnybrook Hlth Sci Ctr, Hurvitz Brain Sci Res Program, Toronto, ON, Canada
Matias-Guiu, JA:
Univ Complutense Madrid, San Carlos Hlth Res Inst, San Carlos Clin Hosp, Dept Neurol & Nucl Med, Madrid, Spain
Cabrera-Martin, MN:
Univ Complutense Madrid, San Carlos Hlth Res Inst, San Carlos Clin Hosp, Dept Neurol & Nucl Med, Madrid, Spain
Paquet, C:
Lariboisiere Fernand Widal Hosp, Dept Neurol, Memory Ctr, Paris, France
Lariboisiere Fernand Widal Hosp, Dept Pathol, Paris, France
Dumurgier, J:
Lariboisiere Fernand Widal Hosp, Dept Neurol, Memory Ctr, Paris, France
Teichmann, M:
Hop La Pitie Salpetriere, AP HP, Natl Reference Ctr PPA & Rare Dementias, Dept Neurol, Paris, France
Sarazin, M:
CEA, CNRS, Frederic Joliot Hosp Serv, ERL 9218, Orsay, Ile De France, France
Univ Paris Sud, CEA, INSERM, IMIV,UMR 1023, Orsay, Ile De France, France
Bottlaender, M:
CEA, CNRS, Frederic Joliot Hosp Serv, ERL 9218, Orsay, Ile De France, France
Univ Paris Sud, CEA, INSERM, IMIV,UMR 1023, Orsay, Ile De France, France
Dubois, B:
Pitie Salpetriere Univ Hosp, Ctr Cognit & Behav Dis, Paris, France
Rowe, CC:
Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia
Univ Melbourne, Dept Med, Melbourne, Vic, Australia
Villemagne, VL:
Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia
Univ Melbourne, Dept Med, Melbourne, Vic, Australia
Vandenberghe, R:
Univ Hosp Leuven, Dept Neurol, Leuven, Belgium
Granadillo, E:
Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA
VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA
Teng, E:
Univ Calif Los Angeles, Dept Neurol, Neurobehav Serv, Los Angeles, CA 90024 USA
Mendez, M:
West Angeles VA Med Ctr, Neurobehav Unit, Los Angeles, CA USA
Meyer, PT:
Univ Hosp Freiburg, Fac Med, Dept Nucl Med, Freiburg, Germany
Frings, L:
Univ Hosp Freiburg, Fac Med, Dept Nucl Med, Freiburg, Germany
Lleo, A:
Santa Cruz & St Paul Hosp, Dept Neurol, Memory Unit, Barcelona, Spain
Autonomous Univ Barcelona, St Paul Biomed Res Inst, Barcelona, Spain
Ctr Biomed Network Res Neurodegenerat Dis, Madrid, Spain
Blesa, R:
Santa Cruz & St Paul Hosp, Dept Neurol, Memory Unit, Barcelona, Spain
Autonomous Univ Barcelona, St Paul Biomed Res Inst, Barcelona, Spain
Fortea, J:
Santa Cruz & St Paul Hosp, Dept Neurol, Memory Unit, Barcelona, Spain
Autonomous Univ Barcelona, St Paul Biomed Res Inst, Barcelona, Spain
Seo, SW:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea
Diehl-Schmid, J:
Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany
Grimmer, T:
Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany
Frederiksen, KS:
Danish Dementia Res Ctr, Dept Neurol, Copenhagen, Denmark
Sanchez-Juan, P:
Marques Valdecilla Univ Hosp, Neurol Serv, Santander, Spain
Chetelat, G:
Univ Caen Normandy, INSERM, UMRS, U1237, Caen, France
Jansen, W:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Banner Alzheimers Inst, Phoenix, AZ USA
Bouchard, RW:
Laval Univ, Interdisciplinary Clin Memory Child Jesus, Quebec City, PQ, Canada
Laforce, RJ:
Laval Univ, Interdisciplinary Clin Memory Child Jesus, Quebec City, PQ, Canada
Univ Laval, CHU Quebec, Clin Interdisciplinaire Memoire Enfant Jesus, Quebec City, PQ, Canada
Visser, PJ:
UIC Barcelona, Catalan Inst Appl Neurosci, ACE Fdn, Llobregat Hosp, Barcelona, Spain
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Ossenkoppele, R:
Vrije Univ Amsterdam, Amsterdam Neurosci, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden
Green Accepted, Green Published
|