• Rik Ossenkoppele, Willemijn J Jansen, Gil D Rabinovici, Dirk L Knol, Wiesje M van der Flier, Bart N M van Berckel, Philip Scheltens, Pieter Jelle Visser, Amyloid PET Study Group, Sander C J Verfaillie, Marissa D Zwan, Sofie M Adriaanse, Adriaan A Lammertsma, Frederik Barkhof, William J Jagust, Bruce L Miller, Howard J Rosen, Susan M Landau, Victor L Villemagne, Christopher C Rowe, Dong Y Lee, Duk L Na, Sang W Seo, Marie Sarazin, Catherine M Roe, Osama Sabri, Henryk Barthel, Norman Koglin, John Hodges, Cristian E Leyton, Rik Vandenberghe, Koen van Laere, Alexander Drzezga, Stefan Forster, Timo Grimmer, Pascual Sánchez-Juan, Jose M Carril, Vincent Mok, Vincent Camus, William E Klunk, Ann D Cohen, Philipp T Meyer, Sabine Hellwig, Andrew Newberg, Kristian S Frederiksen, Adam S Fleisher, Mark A Mintun, David A Wolk, Agneta Nordberg, Juha O Rinne, Gaël Chételat, Alberto Lleo, Rafael Blesa, Juan Fortea, Karine Madsen, Karen M Rodrigue, and David J Brooks.
• 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.
• JAMA. 2015 May 19; 313 (19): 193919491939-49.

ImportanceAmyloid-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.ObjectiveTo use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.Data SourcesThe MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.Study SelectionCase 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 SynthesisData 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 MeasuresEstimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.ResultsThe 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 RelevanceAmong 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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