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Journal Articles JAMA Psychiatry Year : 2018

Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia

Willemijn Jansen (1, 2) , Rik Ossenkoppele (3, 4) , Betty Tijms (3) , Anne Fagan (5) , Oskar Hansson (4, 6) , William Klunk (7) , Wiesje van der Flier (8, 9) , Victor Villemagne (10) , Giovanni Frisoni (11, 12) , Adam Fleisher , Alberto Lleó (13, 14, 15) , Mark Mintun , Anders Wallin (16) , Sebastiaan Engelborghs (17, 18) , Duk Na , Gäel Chételat (19) , José Luis Molinuevo (20, 21) , Susan Landau (22) , Niklas Mattsson (4) , Johannes Kornhuber (23) , Osama Sabri , Christopher Rowe , Lucilla Parnetti , Julius Popp , Tormod Fladby , William Jagust , Pauline Aalten , Dong Young Lee , Rik Vandenberghe , Catarina Resende de Oliveira , Elisabeth Kapaki , Lutz Froelich , Adrian Ivanoiu , Tomasz Gabryelewicz , Marcel Verbeek , Páscual Sanchez-Juan , Helmut Hildebrandt , Vincent Camus (24) , Marzena Zboch , David Brooks , Alexander Drzezga , Juha Rinne , Andrew Newberg , Alexandre de Mendonça , Marie Sarazin (25, 26) , Gil Rabinovici , Karine Madsen , Milica Kramberger , Agneta Nordberg , Vincent Mok , Barbara Mroczko , David Wolk , Philipp Meyer , Magda Tsolaki , Philip Scheltens , Frans Verhey , Pieter Jelle Visser , Dag Aarsland , Daniel Alcolea , Myriam Alexander , Ina Almdahl , Steven Arnold , Inês Baldeiras , Henryk Barthel , Bart N.M. van Berckel , Kaj Blennow , Mark van Buchem , Enrica Cavedo (27) , Kewei Chen , Elena Chipi , Ann Cohen , Stefan Förster , Juan Fortea , Kristian Frederiksen , Yvonne Freund-Levi , Olymbia Gkatzima , Mark Forrest Gordon , Timo Grimmer , Harald Hampel (27) , Lucrezia Hausner , Sabine Hellwig , Sanna-Kaisa Herukka , Peter Johannsen , Aleksandra Klimkowicz-Mrowiec , Sebastian Köhler , Norman Koglin , Koen van Laere , Mony de Leon , Viviana Lisetti , Wolfgang Maier , Jan Marcusson , Olga Meulenbroek , Hanne Møllergård , John Morris , Arto Nordlund , Gerald Novak , George Paraskevas , Gayan Perera , Oliver Peters , Inez Ramakers , Lorena Rami , Eloy Rodríguez-Rodríguez , Catherine Roe , Uros Rot , Eckart Rüther , Isabel Santana , Johannes Schröder , Sang Seo , Hilkka Soininen , Luiza Spiru , Erik Stomrud , Hanne Struyfs , Charlotte Teunissen , Stephanie Vos , Linda van Waalwijk van Doorn , Gunhild Waldemar , Åsa Wallin , Jens Wiltfang , Henrik Zetterberg
1 MUMC - School for Mental Health and Neuroscience - Alzheimer Center Limburg
2 Banner Alzheimer's Institute
3 VU - Vrije Universiteit Amsterdam [Amsterdam]
4 Skane University Hospital [Lund]
5 Washington University School of Medicine in St. Louis
6 Skane University Hospital [Malmo]
7 Department of Psychiatry [Pittsburgh]
8 Alzheimercentre, department of Neurology, VU University Medical Center
9 Department of Clinical Epidemiology and Biostatistics, VU Medical Centre, Amsterdam
10 University of Melbourne
11 IRCCS - Centro San Giovanni di Dio, Fatebenefratelli, Brescia
12 UNIGE - Université de Genève = University of Geneva
13 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
14 Santa Cruz and Saint Paul Hospital [Barcelona]
15 Center for Biomedical Network Research on Neurodegenerative Diseases [Barcelona]
16 GU - Göteborgs Universitet = University of Gothenburg
17 UA - University of Antwerp
18 Hospital Network Antwerp Middelheim and Hoge Beuken
19 Laboratoire de Neuropsychologie
20 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
21 Pasqual Maragall Foundation
22 UC Berkeley - University of California [Berkeley]
23 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
24 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
25 UPD5 - Université Paris Descartes - Paris 5
26 Hôpital Sainte-Anne [Paris]
27 ICM - Institut du Cerveau = Paris Brain Institute
Adam Fleisher
  • Function : Author
Mark Mintun
  • Function : Author
Duk Na
  • Function : Author
Osama Sabri
  • Function : Author
Christopher Rowe
  • Function : Author
Lucilla Parnetti
  • Function : Author
Julius Popp
  • Function : Author
Tormod Fladby
  • Function : Author
William Jagust
  • Function : Author
Pauline Aalten
  • Function : Author
Dong Young Lee
  • Function : Author
Rik Vandenberghe
  • Function : Author
Catarina Resende de Oliveira
  • Function : Author
Elisabeth Kapaki
  • Function : Author
Lutz Froelich
  • Function : Author
Adrian Ivanoiu
  • Function : Author
Tomasz Gabryelewicz
  • Function : Author
Marcel Verbeek
  • Function : Author
Páscual Sanchez-Juan
  • Function : Author
Helmut Hildebrandt
  • Function : Author
Marzena Zboch
  • Function : Author
David Brooks
  • Function : Author
Alexander Drzezga
  • Function : Author
Juha Rinne
  • Function : Author
Andrew Newberg
  • Function : Author
Alexandre de Mendonça
  • Function : Author
Gil Rabinovici
  • Function : Author
Karine Madsen
  • Function : Author
Milica Kramberger
  • Function : Author
Agneta Nordberg
  • Function : Author
Vincent Mok
  • Function : Author
Barbara Mroczko
  • Function : Author
David Wolk
  • Function : Author
Philipp Meyer
  • Function : Author
Magda Tsolaki
  • Function : Author
Philip Scheltens
  • Function : Author
Frans Verhey
  • Function : Author
Pieter Jelle Visser
  • Function : Author
Dag Aarsland
  • Function : Author
Daniel Alcolea
  • Function : Author
Myriam Alexander
  • Function : Author
Ina Almdahl
  • Function : Author
Steven Arnold
  • Function : Author
Inês Baldeiras
  • Function : Author
Henryk Barthel
  • Function : Author
Bart N.M. van Berckel
  • Function : Author
Kaj Blennow
  • Function : Author
Mark van Buchem
  • Function : Author
Kewei Chen
  • Function : Author
Elena Chipi
  • Function : Author
Ann Cohen
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Stefan Förster
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Juan Fortea
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Kristian Frederiksen
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Yvonne Freund-Levi
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Olymbia Gkatzima
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Mark Forrest Gordon
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Timo Grimmer
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Lucrezia Hausner
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Sabine Hellwig
  • Function : Author
Sanna-Kaisa Herukka
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Peter Johannsen
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Aleksandra Klimkowicz-Mrowiec
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Sebastian Köhler
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Norman Koglin
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Koen van Laere
  • Function : Author
Mony de Leon
  • Function : Author
Viviana Lisetti
  • Function : Author
Wolfgang Maier
  • Function : Author
Jan Marcusson
  • Function : Author
Olga Meulenbroek
  • Function : Author
Hanne Møllergård
  • Function : Author
John Morris
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Arto Nordlund
  • Function : Author
Gerald Novak
  • Function : Author
George Paraskevas
  • Function : Author
Gayan Perera
  • Function : Author
Oliver Peters
  • Function : Author
Inez Ramakers
  • Function : Author
Lorena Rami
  • Function : Author
Eloy Rodríguez-Rodríguez
  • Function : Author
Catherine Roe
  • Function : Author
Uros Rot
  • Function : Author
Eckart Rüther
  • Function : Author
Isabel Santana
  • Function : Author
Johannes Schröder
  • Function : Author
Sang Seo
  • Function : Author
Hilkka Soininen
  • Function : Author
Luiza Spiru
  • Function : Author
Erik Stomrud
  • Function : Author
Hanne Struyfs
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Charlotte Teunissen
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Stephanie Vos
  • Function : Author
Linda van Waalwijk van Doorn
  • Function : Author
Gunhild Waldemar
  • Function : Author
Åsa Wallin
  • Function : Author
Jens Wiltfang
  • Function : Author
Henrik Zetterberg
  • Function : Author

Abstract

Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. Design, setting, and participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main outcomes and measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype. Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years. Conclusions and relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

Dates and versions

hal-04557184 , version 1 (24-04-2024)

Identifiers

Cite

Willemijn Jansen, Rik Ossenkoppele, Betty Tijms, Anne Fagan, Oskar Hansson, et al.. Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry, 2018, 75 (1), pp.84. ⟨10.1001/jamapsychiatry.2017.3391⟩. ⟨hal-04557184⟩
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