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Ann Neurol. 2018 Sep 26. doi: 10.1002/ana.25333. [Epub ahead of print]

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

Author information

1
Université Laval, Clinique Interdisiplinaire de Mémoire de l'Enfant-Jésus, Quebec, QC, Canada.
2
VU University Medical Center, Alzheimer Center, Department of Neurology, Amsterdam, Netherlands.
3
University of California San Fransisco, Memory & Aging Center, Department of Neurology, San Fransisco, CA, USA.
4
L'Hospitalet de Llobregat, Cognition and brain plasticity group [Bellvitge biomedical research institute- IDIBELL], Barcelona, Spain.
5
L'Hospitalet de Llobregat, Fundació ACE. Institut Català de Neurociències Aplicades, UIC-Barcelona, Barcelona, ES.
6
VU University Medical Center, Department of Radiology and Nuclaer Medicine, Amsterdam, Netherlands.
7
University College London, Dementia Research Centre, UCL Institute of Neurology, London, UK.
8
Institut d'investigacions Biomèdiques August Pi i Sunyer, Alzheimer's disease and other cognitive disorders unit, Barcelona, Spain.
9
Medical University of Vienna, Institute of Neurology, Vienna, Austria.
10
Erasmus MC - University Medical Center, Alzheimer center, Department of Neurology, Rotterdam, Netherlands.
11
The University of Sydney, Brain and Mind Centre, School of Medical Sciences, Sydney, Australia.
12
The University of New South Wales, Neuroscience Research Australia and School of Medical Sciences, Sydney, Australia.
13
Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.
14
Rush University, Neurological Sciences, Chicago, IL, USA.
15
Northwestern University Medical School, Cognitive Neurology and Alzheimer Disease Center, Chicago, IL, USA.
16
Hopital de la Timone, Service de Neurologie et de Neuropsychologie, Marseille, France.
17
Université de Toulouse, Inserm, ToNIC, Toulouse NeuroImaging Center, Toulouse, France.
18
Harvard Medical School, Frontotemporal Dementia Unit, Department of Neurology, Massachusetts Alzheimer's Disease Research Center, Boston, MA, USA.
19
University of British Columbia, Division of Neurology, Department of Medicine, Vancouver, Canada.
20
University of Pennsylvania, Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA.
21
University of Pennsylvania, Department of Neurology, Philadelphia, PA, USA.
22
University of Pennsylvania, the Penn Frontotemporal Degeneration Center, Philadelphia, PA, USA.
23
Greater Manchester Neurosciences Centre, Cerebral Function Unit, Manchester, UK.
24
University of Manchester, School of Community-Based Medicine, Manchester, UK.
25
University of Manchester, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester, UK.
26
Neurological Research Institute (FLENI), Center of Aging and Memory, Buenos Aires, Argentina.
27
University of Bourgogne Franche-Comté (UBFC), Regional Memory Center (CMRR), Department of Neurology, CHRU Besançon and Integrative and clinical Neurosciences Lab, Besançon, France.
28
Vita-Salute University and IRCCS-San Raffaele Hospital, Department of Neurology, INSPE, Milan, Italy.
29
Université Lille Nord de France, INSERM U1171, Lille, France.
30
Lund University, Clinical Memory Research Unit, Department of Clinical Sciences, Lund, Sweden.
31
Skåne University Hospital, Neuropsychiatric Clinic, Malmö, Sweden.
32
Sunnybrook Health Sciences Centre, University of Toronto, Anatomical Pathology, Toronto, ON, Canada.
33
Sunnybrook Health Sciences Centre, University of Toronto, Department of Medicine (Neurology), Toronto, ON, Canada.
34
Sunnybrook Health Sciences Centre, University of Toronto, Hurvitz Brain Sciences Research Program, Toronto, ON, Canada.
35
Hospital Clinico San Carlos, San Carlos Health Research Institute, Universidad Complutense, Department of Neurology and Nuclear Medicine, Madrid, Spain.
36
Lariboisière-Fernand-Widal Hospital, Memory Center, Department of Neurology, Paris, France.
37
Lariboisière-Fernand-Widal Hospital, Department of Pathology, Paris, France.
38
Université Paris Descartes, Sorbonne Paris Cité, Centre Hospitalier Sainte Anne, Unit of Neurology of Memory and Language, Paris, France.
39
Service Hospitalier Frederic Joliot, ERL 9218 CNRS, CEA, Orsay, Île-de-France, France.
40
Universite Paris-Sud, IMIV, UMR 1023 Inserm, CEA, Orsay, Île-de-France, France.
41
Hôpital Universitaire de la Pitié Salpêtrière, Centre des Maladies Cognitives et Comportementales, Paris, France.
42
Austin Health, Department of Molecular Imaging & Therapy, Melbourne, VIC, Australia.
43
University of Melbourne, Department of Medicine, Melbourne, VIC, Australia.
44
University Hospital Leuven, Department of Neurology, Leuven, Belgium.
45
University of California Los Angeles, Department of Neurology, Los Angeles, CA, USA.
46
VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
47
University of California Los Angeles, Department of Neurology, Neurobehavior Service, Los Angeles, CA, USA.
48
West Los Angeles VA Medical Center, Neurobehavior Unit, Los Angeles, CA, USA.
49
University Hospital of Freiburg, Department of Nuclear Medicine, Faculty of Medicine, Freiburg, Germany.
50
Hospital de la Santa Creu i Sant Pau, Memory Unit, Department of Neurology, Barcelona, Spain.
51
Universitat Autónoma de Barcelona, Biomedical Research Institute Sant Pau, Barcelona, Spain.
52
Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas, Madrid, Madrid, Spain.
53
Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Neurology, Seoul, South-Korea.
54
Technische Universität München, Department of Psychiatry and Psychotherapy, München, Germany.
55
Danish Dementia Research Center, Department of Neurology, Copenhagen, Denmark.
56
Universitary Hospital Marqués de Valdecilla, Neurology Service, Santander, Spain.
57
Université de Caen-Normandie, Inserm UMR-S U1237, Caen, France.
58
Maastricht University, Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht, Netherlands.
59
Banner Alzheimer's Institute, Phoenix, AZ, USA.
60
Université Laval, Faculté de Médecine, Département des Sciences Neurologiques, Quebec, QC, Canada.

Abstract

OBJECTIVE:

To estimate the prevalence of amyloid-positivity, defined by PET/CSF biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.

METHODS:

We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n=443], non-fluent [nfvPPA, n=333], semantic [svPPA, n=401] and mixed/unclassifiable [PPA-M/U, n=74] variants of PPA) from 36 centers, with a measure of amyloid-β 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) ε4 status was determined using generalized estimating equation models.

RESULTS:

Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%) (p<0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 to 27% at age 80, p<0.01) and svPPA (from 6% at age 50 to 32% at age 80, p<0.001), but not in lvPPA (p=0.94). Across PPA variants, APOE ε4 carriers were more often amyloid-β positive (58.0%) than non-carriers (35.0%, p<0.001). Autopsy data revealed Alzheimer's disease (AD) 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%).

INTERPRETATION:

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 taken into account when interpreting Aβ biomarkers in PPA patients. This article is protected by copyright. All rights reserved.

PMID:
30255971
DOI:
10.1002/ana.25333

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