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

Jansen WJ, Ossenkoppele R, Tijms BM, Fagan AM, Hansson O, Klunk WE, Van Der Flier WM, Villemagne VL, Frisoni GB, Fleisher AS, Lleo A, Mintun MA, Wallin A, Engelborghs S, Na DL, Chetelat G, Molinuevo JL, Landau SM, Mattsson N, Kornhuber J, Sabri O, Rowe CC, Parnetti L, Popp J, Fladby T, Jagust WJ, Aalten P, Lee DY, Vandenberghe R, De Oliveira CR, Kapaki E, Froelich L, Ivanoiu A, Gabryelewicz T, Verbeek MM, Sanchez-Juan P, Hildebrandt H, Camus V, Zboch M, Brooks DJ, Drzezga A, Rinne JO, Newberg A, De Mendonca A, Sarazin M, Rabinovici GD, Madsen K, Kramberger MG, Nordberg A, Mok V, Mroczko B, Wolk DA, Meyer PT, Tsolaki M, Scheltens P, Verhey FRJ, Visser PJ (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 75

Pages Range: 84-95

Journal Issue: 1

DOI: 10.1001/jamapsychiatry.2017.3391

Abstract

Cerebral amyloid-? 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.To investigate whether amyloid-? aggregation is associated with cognitive functioning in persons without dementia.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.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.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.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.

Authors with CRIS profile

Involved external institutions

Lund University / Lunds universitet Sweden (SE) Centre Hospitalier Universitaire de Caen France (FR) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH) National and Kapodistrian University of Athens Greece (GR) Universität zu Köln Germany (DE) Ljubljana University Medical Centre (Ljubljana UMC) / Univerzitetni klinični center Ljubljana Slovenia (SI) Thomas Jefferson University United States (USA) (US) Centre Hospitalier Régional Universitaire de Tours France (FR) Universitätsklinikum Freiburg Germany (DE) Maastricht University Netherlands (NL) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) University of Pennsylvania United States (USA) (US) University of California, Berkeley United States (USA) (US) University of Lisbon / Universidade de Lisboa (ULisboa) Portugal (PT) University of Antwerp / Universiteit Antwerpen Belgium (BE) University of Paris 5 - René Descartes / Université Paris V René Descartes France (FR) Klinikum Bremen-Ost Germany (DE) Sungkyunkwan University (SKKU) Korea, Republic of (KR) Akershus University Hospital / Akershus universitetssykehus (Ahus) Norway (NO) Polska Akademia Nauk (PAN) / Polish Academy of Sciences Poland (PL) University of Pittsburgh United States (USA) (US) Copenhagen University Hospital Denmark (DK) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Universidade de Coimbra Portugal (PT) Aristotle University of Thessaloniki Greece (GR) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) Spain (ES) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Banner Sun Health Research Institute United States (USA) (US) Università degli Studi di Perugia Italy (IT) Austin Health Australia (AU) University of Gothenburg / Göteborgs universitet Sweden (SE) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) University of Turku / Turun yliopisto Finland (FI) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Université Catholique de Louvain (UCL) Belgium (BE) University of Białystok Poland (PL) Washington University in St. Louis United States (USA) (US) Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Spain (ES) Hospital de la Santa Creu i Sant Pau Spain (ES) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universität Leipzig Germany (DE) IRCCS Fatebenefratelli - Brescia Italy (IT) Avid Radiopharmaceuticals, Inc., United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE)

How to cite

APA:

Jansen, W.J., Ossenkoppele, R., Tijms, B.M., Fagan, A.M., Hansson, O., Klunk, W.E.,... Visser, P.J. (2018). Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry, 75(1), 84-95. https://doi.org/10.1001/jamapsychiatry.2017.3391

MLA:

Jansen, Willemijn J., et al. "Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia." JAMA Psychiatry 75.1 (2018): 84-95.

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