title: Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 2Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands 3Memory and Aging Center, University of Californ.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, the Netherlands.
authors.forename: Willemijn J
authors.initials: WJ
authors.lastname: Jansen
authors.affiliation: Memory and Aging Center, University of California, San Francisco4Helen Wills Neuroscience Institute, University of California, Berkeley.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 6Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 5Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, the Netherlan.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 2Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sander C J
authors.initials: SC
authors.lastname: Verfaillie
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 2Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Marissa D
authors.initials: MD
authors.lastname: Zwan
authors.affiliation: Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands 2Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sofie M
authors.initials: SM
authors.lastname: Adriaanse
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley7Lawrence Berkeley National Laboratory, University of California, Berkeley.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: Memory and Aging Center, University of California, San Francisco.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, University of California, San Francisco.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley7Lawrence Berkeley National Laboratory, University of California, Berkeley.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Landau
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: Department of Neuropsychiatry, College of Medicine, Seoul National University, South Korea.
authors.forename: Dong Y
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Sungkyunkwan University, Seoul, South Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Department of Neurology, Sungkyunkwan University, Seoul, South Korea.
authors.forename: Sang W
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Neurologie de la Mémoire et du Langage, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Université Paris Descartes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Sarazin
authors.affiliation: Department of Neurology, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany.
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany.
authors.forename: Henryk
authors.initials: H
authors.lastname: Barthel
authors.affiliation: Piramal Imaging, Berlin, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Koglin
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Hodges
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Leyton
authors.affiliation: Laboratory for Cognitive Neurology and Alzheimer Research Center, Katholieke Universiteit Leuven, Catholic University Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Laboratory for Cognitive Neurology and Alzheimer Research Center, Katholieke Universiteit Leuven, Catholic University Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: van Laere
authors.affiliation: Department of Nuclear Medicine, University of Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Forster
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: IFIMAV and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital, Cantabria, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
authors.affiliation: Department of Nuclear Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Carril
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, China.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mok
authors.affiliation: INSERM U930 and Université François Rabelais de Tours, Centre Hospitalier Régional Universitaire Hôpitaux de Tours, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Camus
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ann D
authors.initials: AD
authors.lastname: Cohen
authors.affiliation: Department of Nuclear Medicine, University Hospital Freiburg, Germany.
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Centre for Geriatrics and Gerontology, University Hospital Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hellwig
authors.affiliation: Myrna Brind Center of Integrative Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Newberg
authors.affiliation: Danish Dementia Research Center, Department of Neurology, Righospitalet, University of Copenhagen, Denmark.
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Frederiksen
authors.affiliation: The Banner Alzheimer's Institute, Phoenix, Arizona.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.affiliation: Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.affiliation: Turku PET Centre and Division of Clinical Neuroscience, Turku University Hospital, University of Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: Institut National de la Santé et de la Recherche Medicale, Caen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
authors.affiliation: Department of Neurology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleo
authors.affiliation: Department of Neurology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Department of Neurology, Universitat Autònoma de Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Denmark, Germany.
authors.forename: Karine
authors.initials: K
authors.lastname: Madsen
authors.affiliation: Center for Longevity, The University of Texas at Dallas.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Rodrigue
authors.affiliation: University of Texas Southwestern Medical Center, Dallas39Division of Neuroscience and Medical Research Council Clinical Sciences Centre, Imperial College London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000032:analysis*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D015995:Prevalence; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4