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JAMA. 2015 May 19;313(19):1939-49. doi: 10.1001/jama.2015.4669.

Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis.

Author information

1
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.
2
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, the Netherlands.
3
Memory and Aging Center, University of California, San Francisco4Helen Wills Neuroscience Institute, University of California, Berkeley.
4
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
5
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.
6
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
7
Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
8
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.
9
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.
10
Helen Wills Neuroscience Institute, University of California, Berkeley7Lawrence Berkeley National Laboratory, University of California, Berkeley.
11
Memory and Aging Center, University of California, San Francisco.
12
Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
13
Department of Neuropsychiatry, College of Medicine, Seoul National University, South Korea.
14
Department of Neurology, Sungkyunkwan University, Seoul, South Korea.
15
Neurologie de la Mémoire et du Langage, Sorbonne Paris Cité, INSERM UMR S894, Centre Hospitalier Sainte Anne, Université Paris Descartes, France.
16
Department of Neurology, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri.
17
Department of Nuclear Medicine, University of Leipzig, Germany.
18
Piramal Imaging, Berlin, Germany.
19
Neuroscience Research Australia, Sydney, Australia.
20
Laboratory for Cognitive Neurology and Alzheimer Research Center, Katholieke Universiteit Leuven, Catholic University Leuven, Belgium.
21
Department of Nuclear Medicine, University of Cologne, Germany.
22
Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich, Germany.
23
Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technische Universitaet Muenchen, Munich, Germany.
24
IFIMAV and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital, Cantabria, Spain.
25
Department of Nuclear Medicine, Marqués de Valdecilla University Hospital, University of Cantabria, Spain.
26
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, China.
27
INSERM U930 and Université François Rabelais de Tours, Centre Hospitalier Régional Universitaire Hôpitaux de Tours, France.
28
Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
29
Department of Nuclear Medicine, University Hospital Freiburg, Germany.
30
Centre for Geriatrics and Gerontology, University Hospital Freiburg, Germany.
31
Myrna Brind Center of Integrative Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania.
32
Danish Dementia Research Center, Department of Neurology, Righospitalet, University of Copenhagen, Denmark.
33
The Banner Alzheimer's Institute, Phoenix, Arizona.
34
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
35
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania.
36
Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
37
Turku PET Centre and Division of Clinical Neuroscience, Turku University Hospital, University of Turku, Finland.
38
Institut National de la Santé et de la Recherche Medicale, Caen, France.
39
Department of Neurology, Universitat Autònoma de Barcelona, Spain.
40
Neurobiology Research Unit, Copenhagen University Hospital, Denmark, Germany.
41
Center for Longevity, The University of Texas at Dallas.
42
University of Texas Southwestern Medical Center, Dallas39Division of Neuroscience and Medical Research Council Clinical Sciences Centre, Imperial College London, United Kingdom.

Abstract

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.

PMID:
25988463
PMCID:
PMC4517678
DOI:
10.1001/jama.2015.4669
[Indexed for MEDLINE]
Free PMC Article

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