Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia
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Abstract
IMPORTANCE: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
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The record
- Venue
- JAMA
- Topic
- Dementia and Cognitive Impairment Research
- Field
- Medicine
- Canadian institutions
- —
- Funders
- CilagJanssen PharmaceuticalsNational Institute of Biomedical Imaging and BioengineeringNational Institute on AgingKrajowy Naukowy Osrodek WiodacySahlgrenska AkademinNational Health and Medical Research CouncilMedical Research CouncilCharles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. LouisUniversity of California, San DiegoGenentechChinese University of Hong KongNational Institutes of HealthVlaamse regeringNational Research CentreAcademy of FinlandServierInnovative Medicines InitiativeUniwersytet Medyczny im. Piastów Slaskich we WroclawiuIndian Council of Medical ResearchRheinische Friedrich-Wilhelms-Universität BonnUniversität zu KölnSundhed og Sygdom, Det Frie ForskningsrådRégion NormandieUniversitatea de Medicină şi Farmacie "Carol Davila" BucureştiFondation pour la Recherche sur AlzheimerRadboud Universitair Medisch CentrumCenter for Translational Molecular MedicineEli Lilly and CompanyUniversidade de LisboaMerz PharmaceuticalsGöteborgs UniversitetEuropean Federation of Pharmaceutical Industries and AssociationsBayer HealthCareInstitut National de la Santé et de la Recherche MédicaleH. Lundbeck A/SUniversité Pierre et Marie CurieUniversidade de CoimbraTurun YliopistoDeutsches Zentrum für Neurodegenerative ErkrankungenBelgian Federal Science Policy OfficeRigshospitaletNational and Kapodistrian University of AthensEisaiLeids Universitair Medisch CentrumKuopion Yliopistollinen SairaalaKarolinska InstitutetLunds UniversitetFonds Wetenschappelijk OnderzoekDementia Collaborative Research Centres, AustraliaF. Hoffmann-La RocheUniversité de GenèveVrije Universiteit AmsterdamRadboud UniversiteitUniversität HeidelbergUniversiteit van AmsterdamYork UniversityUniversiteit LeidenSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungTechnische Universität MünchenImperial College LondonGentofte HospitalDeutsche ForschungsgemeinschaftU.S. Department of DefenseSamsungCommonwealth Scientific and Industrial Research OrganisationMinistero della SaluteJanssen Research and DevelopmentAstraZenecaCanadian Institutes of Health ResearchEuropean CommissionLui Che Woo Institute of Innovative MedicineAristotle University of ThessalonikiZonMwIXICOTurun Yliopistollinen KeskussairaalaPostgraduate Institute of Medical Education and Research, ChandigarhInstituto de Investigación Marqués de ValdecillaAvid RadiopharmaceuticalsPfizerEU Joint Programme – Neurodegenerative Disease ResearchSorbonne UniversitéUniversiteit AntwerpenNorthern California Institute for Research and EducationAlzheimer's AssociationScience and Industry Endowment FundUniversità degli Studi di PerugiaEuropean Regional Development FundSeoul National UniversityKU LeuvenUniversity of PittsburghUniversity of PennsylvaniaAgence Nationale de la RechercheBiogenBioClinicaCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasItä-Suomen YliopistoEdith Cowan UniversityBundesministerium für Bildung und ForschungMedpaceSungkyunkwan UniversityEmory UniversityInstituto de Salud Carlos IIISynarcFoundation for the National Institutes of HealthUniversity of Southern CaliforniaGlaxoSmithKlineBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeLundbeckfondenAXA Research FundMeso Scale DiagnosticsMenzies Centre for Australian Studies, King's College London, University of LondonThomas Jefferson UniversityNational Science Foundation
- Keywords
- MedicineDementiaAmyloid (mycology)PathologyDisease
- Has abstract in OpenAlex
- yes