Prevalence of Amyloid PET Positivity in Dementia Syndromes

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Résumé

IMPORTANCE: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes. DATA SOURCES: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies. STUDY SELECTION: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data. DATA EXTRACTION AND SYNTHESIS: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy). MAIN OUTCOMES AND MEASURES: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method. RESULTS: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years. CONCLUSIONS AND RELEVANCE: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years.

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La notice

Revue

JAMA

Thématique

Dementia and Cognitive Impairment Research

Domaine

Medicine

Établissements canadiens

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Organismes subventionnaires

National Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Neurological Disorders and StrokeNational Institute on AgingHealth and Health Services Research FundCharles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. LouisCanadian Institutes of Health ResearchUniversity of California, San DiegoPfizerUniversity of California, Los AngelesAstraZenecaEuropean CommissionGenentechNational Institutes of HealthRégion NormandieUniversity of Texas at DallasIXICOTurun Yliopistollinen KeskussairaalaMedical Research CouncilServierUniversitat Autònoma de BarcelonaUniversidad de CantabriaTurun YliopistoKarolinska InstitutetEisaiDementia Collaborative Research Centres, AustraliaTechnische Universität MünchenDeutsche ForschungsgemeinschaftGentofte HospitalCommonwealth Scientific and Industrial Research OrganisationInstitut National de la Santé et de la Recherche MédicaleBayer HealthCareCenter for Translational Molecular MedicineAvid RadiopharmaceuticalsUniversity of PittsburghWashington University in St. LouisSynarcImperial College LondonLui Che Woo Institute of Innovative MedicineNorthern California Institute for Research and EducationEuropean Federation of Pharmaceutical Industries and AssociationsAlzheimer's AssociationF. Hoffmann-La RocheAmorfix Life SciencesThomas Jefferson UniversityBiogenBioClinicaUniversity of PennsylvaniaBristol-Myers SquibbAmerican Parkinson Disease AssociationJanssen Alzheimer Immunotherapy Research And DevelopmentScience and Industry Endowment FundNational Health and Medical Research CouncilEdith Cowan UniversityMedpaceEli Lilly and CompanyAlzheimer's Disease Neuroimaging InitiativeMeso Scale Diagnostics

Mots-clés

MedicineDementiaAmyloid (mycology)PathologyDisease

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