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

2018-01-01

Jansen, Willemijn J

Ossenkoppele, Rik

Tijms, Betty M

Fagan, Anne M

Hansson, Oskar

Klunk, William E

van der Flier, Wiesje M

Villemagne, Victor L

Frisoni, Giovanni B

Fleisher, Adam S

Lleó, Alberto

Morris, John C

Nordlund, Arto

Novak, Gerald P

Paraskevas, George P

Perera, Gayan

Peters, Oliver

Ramakers, Inez H G B

Rodríguez-Rodríguez, Eloy

Roe, Catherine M

Rot, Uros

Teunissen, Charlotte E

Rüther, Eckart

Santana, Isabel

Schröder, Johannes

Seo, Sang W

Soininen, Hilkka

Spiru, Luiza

Mintun, Mark A

Stomrud, Erik

Struyfs, Hanne

Vos, Stephanie J B

van Waalwijk van Doorn, Linda J C

Waldemar, Gunhild

Wallin, Åsa K

Wiltfang, Jens

Zetterberg, Henrik

Wallin, Anders

Engelborghs, Sebastiaan

Na, Duk L

Fladby, Tormod

Chételat, Gäel

Molinuevo, José Luis

Landau, Susan M

Mattsson, Niklas

Kornhuber, Johannes

Sabri, Osama

Rowe, Christopher C

Parnetti, Lucilla

Popp, Julius

Jagust, William J

Aalten, Pauline

Lee, Dong Young

Vandenberghe, Rik

Resende de Oliveira, Catarina

Kapaki, Elisabeth

Froelich, Lutz

Ivanoiu, Adrian

Gabryelewicz, Tomasz

de Mendonça, Alexandre

Verbeek, Marcel M

Sanchez-Juan, Páscual

Hildebrandt, Helmut

Camus, Vincent

Zboch, Marzena

Brooks, David J

Drzezga, Alexander

Rinne, Juha O

Newberg, Andrew

Sarazin, Marie

Rabinovici, Gil D

Madsen, Karine

Kramberger, Milica G

Nordberg, Agneta

Mok, Vincent

Mroczko, Barbara

Wolk, David A

Meyer, Philipp T

Baldeiras, Inês

Tsolaki, Magda

Scheltens, Philip

Verhey, Frans R J

Visser, Pieter Jelle

Aarsland, Dag

Alcolea, Daniel

Alexander, Myriam

Almdahl, Ina S

Arnold, Steven E

Barthel, Henryk

van Berckel, Bart N M

Blennow, Kaj

van Buchem, Mark A

Cavedo, Enrica

Chen, Kewei

Chipi, Elena

Cohen, Ann D

Förster, Stefan

Herukka, Sanna-Kaisa

Fortea, Juan

Frederiksen, Kristian S

Freund-Levi, Yvonne

Gkatzima, Olymbia

Gordon, Mark Forrest

Grimmer, Timo

Hampel, Harald

Hausner, Lucrezia

Hellwig, Sabine

Johannsen, Peter

Klimkowicz-Mrowiec, Aleksandra

Köhler, Sebastian

Koglin, Norman

van Laere, Koen

de Leon, Mony

Lisetti, Viviana

Maier, Wolfgang

Marcusson, Jan

Rami, Lorena

Meulenbroek, Olga

Møllergård, Hanne M

Journal Article

0000-0003-3910-2453

10.1001/jamapsychiatry.2017.3391

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. To investigate whether amyloid-β 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.

link

JAMA psychiatry 2018; 75(1): 84-95

JAMA psychiatry