Association of cerebral amyloid-β aggregation with cognitive functioning in persons without dementia

Association of cerebral amyloid-β aggregation with cognitive functioning in persons without dementia

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 trial...

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Veröffentlicht in:JAMA Psychiatry 2018, Vol.75 (1), p.84-95
Hauptverfasser: Jansen, Willemijn, Ossenkoppele, Rik, Tijms, Betty, Fagan, Anne, Hansson, Oskar, Klunk, William, van der Flier, Wiesje, Villemagne, Victor, Frisoni, Giovanni, Fleisher, Adam, Lleo, Alberto, Mintun, Mark, Wallin, Anders, Engelborghs, Sebastiaan, Na, Duk, Chételat, Gael, Molinuevo, José, Landau, Susan, Mattsson, Niklas, Kornhuber, Johannes, Sabri, Osama, Rowe, Christopher, Parnetti, Lucilla, Popp, Julius, Fladby, Tormod, Jagust, William, Aalten, Pauline, Lee, Dong, Vandenberghe, Rik, Resende de Oliveira, Catarina, Kapaki, Elisabeth, Froelich, Lutz, Ivanoiu, Adrian, Gabryelewicz, Tomasz, Verbeek, Marcel, Sanchez-Juan, Pascual, Hildebrandt, Helmut, Camus, Vincent, Zboch, Marzena, Brooks, David, Drzezga, Alexander, Rinne, Juha, Newberg, Andrew, de Mendonça, Alexandre, Sarazin, Marie, Rabinovici, Gil, Madsen, Karine, Kramberger, Milica, Nordberg, Agneta, Mok, Vincent, Mroczko, Barbara, Wolk, David, Meyer, Philipp, Tsolaki, Magda, Scheltens, Philip, Verhey, Frans, Visser, Pieter, Alcolea, Daniel, Alexander, Myriam, Aarsland, Dag, Arnold, Steven, Baldeiras, Ines, Barthel, Henryk, van Berckel, Bart, Blennow, Kaj, van Buchem, Mark, Cavedo, Enrica, Chen, Kewei, Chipi, Elena, Cohen, Ann, Forster, Stefan, Fortea, Juan, Frederiksen, Kristian, Freund-Levi, Yvonne, Gkatzima, Olymbia, Gordon, Mark, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna Kaisa, Johannsen, Peter, Klimkowicz-Mrowiec, Aleksandra, Kohler, Sebastian, Koglin, Norman, Van Laere, Koen, de Leon, Mony, Lisetti, Viviana, Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Mollergard, Hanne, Morris, John, Nordlund, Arto, Novak, Gerald, Paraskevas, George, Perera, Gayan, Peters, Oliver, Ramakers, Inez, Rami, Lorena
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Zusammenfassung: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 
ISSN:2168-622X