Jansen, Willemijn J., Ossenkoppele, Rik, Tijms, Betty M. ORCID: 0000-0002-2612-1797, Fagan, Anne M., Hansson, Oskar ORCID: 0000-0001-8467-7286, Klunk, William E., van der Flier, Wiesje M., Villemagne, Victor L., Frisoni, Giovanni B., Fleisher, Adam S., Lleo, Alberto, Mintun, Mark A., Wallin, Anders, Engelborghs, Sebastiaan, Na, Duk L., Chetelat, Gael, Molinuevo, Jose Luis ORCID: 0000-0003-0485-6001, Landau, Susan M., Mattsson, Niklas, Kornhuber, Johannes ORCID: 0000-0002-8096-3987, Sabri, Osama, Rowe, Christopher C., Parnetti, Lucilla ORCID: 0000-0001-5722-3967, Popp, Julius ORCID: 0000-0002-0068-0312, Fladby, Tormod ORCID: 0000-0002-9984-9797, Jagust, William J., Aalten, Pauline, Lee, Dong Young, Vandenberghe, Rik ORCID: 0000-0001-6237-2502, de Oliveira, Catarina Resende, Kapaki, Elisabeth, Froelich, Lutz, Ivanoiu, Adrian, Gabryelewicz, Tomasz, Verbeek, Marcel M., Sanchez-Juan, Pascual, Hildebrandt, Helmut, Camus, Vincent, Zboch, Marzena, Brooks, David J., Drzezga, Alexander, Rinne, Juha O., Newberg, Andrew, de Mendonca, Alexandre ORCID: 0000-0002-0488-1453, Sarazin, Marie, Rabinovici, Gil D., Madsen, Karine, Kramberger, Milica G., Nordberg, Agneta ORCID: 0000-0001-7345-5151, Mok, Vincent ORCID: 0000-0002-8102-8835, Mroczko, Barbara ORCID: 0000-0002-4075-8479, Wolk, David A., Meyer, Philipp T., Tsolaki, Magda ORCID: 0000-0002-2072-8010, Scheltens, Philip ORCID: 0000-0002-1046-6408, Verhey, Frans R. J. and Visser, Pieter Jelle ORCID: 0000-0001-8008-9727 (2018). Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry, 75 (1). S. 84 - 96. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6238

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Abstract

IMPORTANCE Cerebral amyloid-beta 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-beta 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jansen, Willemijn J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ossenkoppele, RikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tijms, Betty M.UNSPECIFIEDorcid.org/0000-0002-2612-1797UNSPECIFIED
Fagan, Anne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansson, OskarUNSPECIFIEDorcid.org/0000-0001-8467-7286UNSPECIFIED
Klunk, William E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Flier, Wiesje M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villemagne, Victor L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frisoni, Giovanni B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fleisher, Adam S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lleo, AlbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mintun, Mark A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wallin, AndersUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engelborghs, SebastiaanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Na, Duk L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chetelat, GaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molinuevo, Jose LuisUNSPECIFIEDorcid.org/0000-0003-0485-6001UNSPECIFIED
Landau, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattsson, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kornhuber, JohannesUNSPECIFIEDorcid.org/0000-0002-8096-3987UNSPECIFIED
Sabri, OsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rowe, Christopher C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parnetti, LucillaUNSPECIFIEDorcid.org/0000-0001-5722-3967UNSPECIFIED
Popp, JuliusUNSPECIFIEDorcid.org/0000-0002-0068-0312UNSPECIFIED
Fladby, TormodUNSPECIFIEDorcid.org/0000-0002-9984-9797UNSPECIFIED
Jagust, William J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aalten, PaulineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Dong YoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vandenberghe, RikUNSPECIFIEDorcid.org/0000-0001-6237-2502UNSPECIFIED
de Oliveira, Catarina ResendeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kapaki, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froelich, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ivanoiu, AdrianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabryelewicz, TomaszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verbeek, Marcel M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Juan, PascualUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hildebrandt, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camus, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zboch, MarzenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rinne, Juha O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Newberg, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Mendonca, AlexandreUNSPECIFIEDorcid.org/0000-0002-0488-1453UNSPECIFIED
Sarazin, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rabinovici, Gil D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madsen, KarineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramberger, Milica G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordberg, AgnetaUNSPECIFIEDorcid.org/0000-0001-7345-5151UNSPECIFIED
Mok, VincentUNSPECIFIEDorcid.org/0000-0002-8102-8835UNSPECIFIED
Mroczko, BarbaraUNSPECIFIEDorcid.org/0000-0002-4075-8479UNSPECIFIED
Wolk, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, Philipp T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsolaki, MagdaUNSPECIFIEDorcid.org/0000-0002-2072-8010UNSPECIFIED
Scheltens, PhilipUNSPECIFIEDorcid.org/0000-0002-1046-6408UNSPECIFIED
Verhey, Frans R. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Visser, Pieter JelleUNSPECIFIEDorcid.org/0000-0001-8008-9727UNSPECIFIED
URN: urn:nbn:de:hbz:38-200602
DOI: 10.1001/jamapsychiatry.2017.3391
Journal or Publication Title: JAMA Psychiatry
Volume: 75
Number: 1
Page Range: S. 84 - 96
Date: 2018
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ALZHEIMERS-DISEASE; MEMORY PERFORMANCE; APOE; DECLINE; AGE; BURDEN; INDIVIDUALS; PREVALENCE; DEPOSITION; PATHOLOGYMultiple languages
PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20060

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