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

2017· article· en· W2768948569 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueJAMA Psychiatry · 2017
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersCilagJanssen PharmaceuticalsNational Center for Research ResourcesNational Institute of Biomedical Imaging and BioengineeringNational Institute on AgingKrajowy Naukowy Osrodek WiodacySahlgrenska AkademinMedizinische Fakultät der Albert-Ludwigs-Universität FreiburgNational Health and Medical Research CouncilMedical Research CouncilCharles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. LouisEuropean CommissionCanadian Institutes of Health ResearchUniversity of California, San FranciscoNational Institutes of HealthGöteborgs UniversitetMerz PharmaceuticalsAkershus UniversitetssykehusBiogenMarcus och Amalia Wallenbergs minnesfondIXICOTurun Yliopistollinen KeskussairaalaNational Research CentreAcademy of FinlandServierUniwersytet Medyczny im. Piastów Slaskich we WroclawiuRheinische Friedrich-Wilhelms-Universität BonnSahlgrenska UniversitetssjukhusetAristotle University of ThessalonikiFondation pour la Recherche sur AlzheimerRadboud Universitair Medisch CentrumEli Lilly and CompanyUniversidade de LisboaUniversität zu KölnBayer HealthCareInstitut National de la Santé et de la Recherche MédicaleH. Lundbeck A/SNational Institute for Health and Care ResearchUniversité Pierre et Marie CurieTurun YliopistoDeutsches Zentrum für Neurodegenerative ErkrankungenSouth London and Maudsley NHS Foundation TrustBelgian Federal Science Policy OfficeRigshospitaletNational and Kapodistrian University of AthensEisaiLeids Universitair Medisch CentrumSundhed og Sygdom, Det Frie ForskningsrådRégion NormandieVetenskapsrådetKuopion Yliopistollinen SairaalaKarolinska InstitutetFonds Wetenschappelijk OnderzoekDementia Collaborative Research Centres, AustraliaMedpaceBundesministerium für Bildung und ForschungRadboud UniversiteitYork UniversitySchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversiteit LeidenAlzheimer's Disease Neuroimaging InitiativeEuropean Regional Development FundKU LeuvenSeoul National UniversityUniversität HeidelbergTechnische Universität MünchenImperial College LondonKing's College LondonGentofte HospitalDeutsche ForschungsgemeinschaftMinistero della SaluteGenentechJanssen Research and DevelopmentAstraZenecaAvid RadiopharmaceuticalsPfizerCentre National de la Recherche ScientifiqueInstituto de Salud Carlos IIISynarcAustralian GovernmentVlaamse regeringLui Che Woo Institute of Innovative MedicineAgence Nationale de la RechercheInstituto de Investigación Marqués de ValdecillaEU Joint Programme – Neurodegenerative Disease ResearchUniversiteit AntwerpenNorthern California Institute for Research and EducationSungkyunkwan UniversityNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchAlzheimer's AssociationThomas Jefferson UniversityUniversità degli Studi di PerugiaUniversity of PittsburghUniversity of PennsylvaniaBioClinicaUniversity of California, San DiegoCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasU.S. Department of DefenseItä-Suomen YliopistoEdith Cowan UniversityLundbeckfondenAlbert-Ludwigs-Universität FreiburgAXA Research FundSamsungFoundation for the National Institutes of HealthUniversity of Southern CaliforniaBristol-Myers SquibbMeso Scale DiagnosticsScience and Industry Endowment FundNational Science Foundation
KeywordsDementiaAssociation (psychology)CognitionAmyloid (mycology)MedicineAlzheimer's diseaseNeurosciencePsychologyPsychiatryClinical psychologyInternal medicineDiseasePathologyPsychotherapist

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.027
Threshold uncertainty score0.411

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.298
Teacher spread0.285 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it