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

Willemijn Jansen; Rik Ossenkoppele; Betty Tijms; Anne Fagan; Oskar Hansson; William Klunk; Wiesje van der Flier; Victor Villemagne; Giovanni Frisoni; Adam Fleisher; Alberto Lleó; Mark Mintun; Anders Wallin; Sebastiaan Engelborghs; Duk Na; Gäel Chételat; José Luis Molinuevo; Susan Landau; Niklas Mattsson; Johannes Kornhuber; 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; Marzena Zboch; David Brooks; Alexander Drzezga; Juha Rinne; Andrew Newberg; Alexandre de Mendonça; Marie Sarazin; 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; Kewei Chen; Elena Chipi; Ann Cohen; Stefan Förster; Juan Fortea; Kristian Frederiksen; Yvonne Freund-Levi; Olymbia Gkatzima; Mark Forrest Gordon; Timo Grimmer; Harald Hampel; 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

doi:10.1001/jamapsychiatry.2017.3391

Journal Articles JAMA Psychiatry Year : 2018

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

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Willemijn Jansen

Function : Author

School for Mental Health and Neuroscience - Alzheimer Center Limburg

Banner Alzheimer's Institute

Rik Ossenkoppele

Function : Author

Vrije Universiteit Amsterdam [Amsterdam]

Skane University Hospital [Lund]

Betty Tijms

Function : Author

Vrije Universiteit Amsterdam [Amsterdam]

Anne Fagan

Function : Author

Washington University School of Medicine in St. Louis

Oskar Hansson

Function : Author

Skane University Hospital [Lund]

Skane University Hospital [Malmo]

William Klunk

Function : Author

Department of Psychiatry [Pittsburgh]

Wiesje van der Flier

Function : Author

Alzheimercentre, department of Neurology, VU University Medical Center

Department of Clinical Epidemiology and Biostatistics, VU Medical Centre, Amsterdam

Victor Villemagne

Function : Author

University of Melbourne

Giovanni Frisoni

Function : Author

Centro San Giovanni di Dio, Fatebenefratelli, Brescia

Université de Genève = University of Geneva

Adam Fleisher

Function : Author

Alberto Lleó

Function : Author

Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona

Santa Cruz and Saint Paul Hospital [Barcelona]

Center for Biomedical Network Research on Neurodegenerative Diseases [Barcelona]

Mark Mintun

Function : Author

Anders Wallin

Function : Author

Göteborgs Universitet = University of Gothenburg

Sebastiaan Engelborghs

Function : Author

University of Antwerp

Hospital Network Antwerp Middelheim and Hoge Beuken

Duk Na

Function : Author

Gäel Chételat

Function : Author

Laboratoire de Neuropsychologie

José Luis Molinuevo

Function : Author

Institut d'Investigacions Biomèdiques August Pi i Sunyer

Pasqual Maragall Foundation

Susan Landau

Function : Author

University of California [Berkeley]

Niklas Mattsson

Function : Author

Skane University Hospital [Lund]

Johannes Kornhuber

Function : Author

Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg

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

Vincent Camus

Function : Author

Centre Hospitalier Régional Universitaire de Tours

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

Marie Sarazin

Function : Author

Université Paris Descartes - Paris 5

Hôpital Sainte-Anne [Paris]

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

Enrica Cavedo

Function : Author

Institut du Cerveau = Paris Brain Institute

Kewei Chen

Function : Author

Elena Chipi

Function : Author

Ann Cohen

Function : Author

Stefan Förster

Function : Author

Juan Fortea

Function : Author

Kristian Frederiksen

Function : Author

Yvonne Freund-Levi

Function : Author

Olymbia Gkatzima

Function : Author

Mark Forrest Gordon

Function : Author

Timo Grimmer

Function : Author

Harald Hampel

Function : Author

Institut du Cerveau = Paris Brain Institute

Lucrezia Hausner

Function : Author

Sabine Hellwig

Function : Author

Sanna-Kaisa Herukka

Function : Author

Peter Johannsen

Function : Author

Aleksandra Klimkowicz-Mrowiec

Function : Author

Sebastian Köhler

Function : Author

Norman Koglin

Function : Author

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

Function : Author

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

Function : Author

Charlotte Teunissen

Function : Author

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.

Domains

Human health and pathology

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https://hal.sorbonne-universite.fr/hal-04557184

Submitted on : Wednesday, April 24, 2024-9:18:38 AM

Last modification on : Thursday, April 25, 2024-2:00:53 PM

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

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HAL Id : hal-04557184 , version 1
DOI : 10.1001/jamapsychiatry.2017.3391
PUBMED : 29188296
PUBMEDCENTRAL : PMC5786156

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

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