Ossenkoppele Rik, Jansen Willemijn J, Rabinovici Gil D, Knol Dirk L, van der Flier Wiesje M, van Berckel Bart N M, Scheltens Philip, Visser Pieter Jelle, Verfaillie Sander C J, Zwan Marissa D, Adriaanse Sofie M, Lammertsma Adriaan A, Barkhof Frederik, Jagust William J, Miller Bruce L, Rosen Howard J, Landau Susan M, Villemagne Victor L, Rowe Christopher C, Lee Dong Y, Na Duk L, Seo Sang W, Sarazin Marie, Roe Catherine M, Sabri Osama, Barthel Henryk, Koglin Norman, Hodges John, Leyton Cristian E, Vandenberghe Rik, van Laere Koen, Drzezga Alexander, Forster Stefan, Grimmer Timo, Sánchez-Juan Pascual, Carril Jose M, Mok Vincent, Camus Vincent, Klunk William E, Cohen Ann D, Meyer Philipp T, Hellwig Sabine, Newberg Andrew, Frederiksen Kristian S, Fleisher Adam S, Mintun Mark A, Wolk David A, Nordberg Agneta, Rinne Juha O, Chételat Gaël, Lleo Alberto, Blesa Rafael, Fortea Juan, Madsen Karine, Rodrigue Karen M, Brooks David J
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.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, the Netherlands.
JAMA. 2015 May 19;313(19):1939-49. doi: 10.1001/jama.2015.4669.
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.
To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.
The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.
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 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).
Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.
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.
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.
淀粉样蛋白β正电子发射断层扫描（PET）成像能够在体内检测到纤维状斑块，这是阿尔茨海默病（AD）的一项核心神经病理学特征。其诊断效用仍不明确，因为淀粉样斑块也会出现在非AD痴呆患者中。
使用个体参与者数据荟萃分析来估计各种痴呆综合征患者PET淀粉样蛋白阳性的患病率。
检索了MEDLINE和科学网数据库，时间跨度为2004年1月至2015年4月，以查找淀粉样PET研究。
排除病例报告以及关于痴呆以外的神经或精神疾病的研究。邀请符合条件队列的通讯作者提供个体参与者数据。
为1359名临床诊断为AD的参与者和538名非AD痴呆参与者提供了数据。参照组为1849名健康对照参与者（基于淀粉样PET）和1369名AD参与者的独立样本（基于尸检）。
使用广义估计方程法，根据诊断、年龄和载脂蛋白E（APOE）ε4状态估计淀粉样PET扫描阳性的患病率。
淀粉样蛋白阳性的可能性与年龄和APOE ε4状态相关。在AD痴呆中，APOE ε4非携带者中淀粉样蛋白阳性的患病率从50岁时的86%[95%CI，73%-94%]降至90岁时的68%[95%CI，57%-77%]（n = 377）；APOE ε4携带者中患病率下降程度较小，从50岁时的97%[95%CI，92%-99%]降至90岁时的90%[95%CI，83%-94%]（n = 593；P < 0.01）。在尸检确诊为AD痴呆的参与者中也观察到年龄和APOE ε4与淀粉样蛋白阳性有类似关联。在大多数非AD痴呆中，淀粉样蛋白阳性率随年龄（从60岁到80岁）和APOE ε4携带者状态而增加（路易体痴呆：携带者[n = 16]，60岁时为63%[95%CI，48%-80%]，80岁时为83%[95%CI，67%-92%]；非携带者[n = 18]，60岁时为29%[95%CI，15%-50%]，80岁时为54%[95%CI，30%-77%]；额颞叶痴呆：携带者[n = 48]，60岁时为19%[95%CI，12%-28%]，80岁时为43%[95%CI，35%-50%]；非携带者[n = 160]，60岁时为5%[95%CI，3%-8%]，80岁时为14%[95%CI，11%-18%]；血管性痴呆：携带者[n = 30]，60岁时为25%[95%CI，9%-52%]，80岁时为64%[95%CI，49%-77%]；非携带者[n = 77]，60岁时为7%[95%CI，3%-18%]，80岁时为29%[95%CI，17%-43%]）。
在痴呆参与者中，淀粉样蛋白阳性的患病率与临床诊断、年龄和APOE基因型相关。这些发现表明淀粉样蛋白成像在早发性痴呆鉴别诊断中的潜在临床效用，以及支持对70岁以上且APOE ε4非携带者状态的AD痴呆参与者进行临床诊断。
