Jansen Willemijn J, Ossenkoppele Rik, Tijms Betty M, Fagan Anne M, Hansson Oskar, Klunk William E, van der Flier Wiesje M, Villemagne Victor L, Frisoni Giovanni B, Fleisher Adam S, Lleó Alberto, Mintun Mark A, Wallin Anders, Engelborghs Sebastiaan, Na Duk L, Chételat Gäel, Molinuevo José Luis, Landau Susan M, Mattsson Niklas, Kornhuber Johannes, Sabri Osama, Rowe Christopher C, Parnetti Lucilla, Popp Julius, Fladby Tormod, Jagust William J, Aalten Pauline, Lee Dong Young, Vandenberghe Rik, Resende de Oliveira Catarina, Kapaki Elisabeth, Froelich Lutz, Ivanoiu Adrian, Gabryelewicz Tomasz, Verbeek Marcel M, Sanchez-Juan Páscual, Hildebrandt Helmut, Camus Vincent, Zboch Marzena, Brooks David J, Drzezga Alexander, Rinne Juha O, Newberg Andrew, de Mendonça Alexandre, Sarazin Marie, Rabinovici Gil D, Madsen Karine, Kramberger Milica G, Nordberg Agneta, Mok Vincent, Mroczko Barbara, Wolk David A, Meyer Philipp T, Tsolaki Magda, Scheltens Philip, Verhey Frans R J, Visser Pieter Jelle, Aarsland Dag, Alcolea Daniel, Alexander Myriam, Almdahl Ina S, Arnold Steven E, Baldeiras Inês, Barthel Henryk, van Berckel Bart N M, Blennow Kaj, van Buchem Mark A, Cavedo Enrica, Chen Kewei, Chipi Elena, Cohen Ann D, Förster Stefan, Fortea Juan, Frederiksen Kristian S, Freund-Levi Yvonne, Gkatzima Olymbia, Gordon Mark Forrest, Grimmer Timo, Hampel Harald, Hausner Lucrezia, Hellwig Sabine, Herukka Sanna-Kaisa, Johannsen Peter, Klimkowicz-Mrowiec Aleksandra, Köhler Sebastian, Koglin Norman, van Laere Koen, de Leon Mony, Lisetti Viviana, Maier Wolfgang, Marcusson Jan, Meulenbroek Olga, Møllergård Hanne M, Morris John C, Nordlund Arto, Novak Gerald P, Paraskevas George P, Perera Gayan, Peters Oliver, Ramakers Inez H G B, Rami Lorena, Rodríguez-Rodríguez Eloy, Roe Catherine M, Rot Uros, Rüther Eckart, Santana Isabel, Schröder Johannes, Seo Sang W, Soininen Hilkka, Spiru Luiza, Stomrud Erik, Struyfs Hanne, Teunissen Charlotte E, Vos Stephanie J B, van Waalwijk van Doorn Linda J C, Waldemar Gunhild, Wallin Åsa K, Wiltfang Jens, Zetterberg Henrik
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
JAMA Psychiatry. 2018 Jan 1;75(1):84-95. doi: 10.1001/jamapsychiatry.2017.3391.
Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.
To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.
Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.
Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.
Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
脑淀粉样β蛋白聚集是阿尔茨海默病（AD）的早期事件。了解无痴呆症人群中淀粉样蛋白聚集与认知表现之间的关联，对于更好地理解AD病程以及预防试验设计具有重要意义。
研究淀粉样β蛋白聚集是否与无痴呆症人群的认知功能相关。
设计、地点和参与者：这项横断面研究纳入了多中心淀粉样生物标志物研究中53项研究的2908名认知正常参与者和4133名轻度认知障碍（MCI）参与者。认知正常定义为无寻求医疗帮助的认知问题且认知测试分数在正常范围内。轻度认知障碍根据已发表标准进行诊断。研究纳入始于2013年且仍在进行中。数据分析于2017年1月进行。
通过简易精神状态检查表（MMSE）评估的总体认知表现，以及通过言语词汇学习测试评估的情景记忆表现。淀粉样蛋白聚集通过正电子发射断层扫描或脑脊液生物标志物进行测量，并根据研究特定的临界值分为阴性（正常）或阳性（异常）。使用广义估计方程来检验淀粉样蛋白聚集与低认知分数（MMSE分数≤27或记忆z分数≤ -1.28）之间的关联，并评估这种关联是否受年龄、性别、教育水平或载脂蛋白E基因型的影响。
在2908名认知正常者（平均[标准差]年龄，67.4[12.8]岁）中，70岁以后淀粉样蛋白阳性与低记忆分数相关（淀粉样蛋白阳性与阴性者的平均差异，72岁时为4%[95%置信区间，0% - 7%]，90岁时为21%[95%置信区间，10% - 33%]），但与低MMSE分数无关（平均差异，3%[95%置信区间， -1%至6%]，P = 0.16）。在4133名MCI患者（平均[标准差]年龄，70.2[8.5]岁）中，淀粉样蛋白阳性与低记忆（平均差异，16%[95%置信区间，12% - 20%]，P < 0.001）和低MMSE（平均差异，14%[95%置信区间，12% - 17%]，P < 0.001）分数相关，且这种关联随年龄降低。低认知分数在筛查认知正常者和MCI患者的淀粉样蛋白阳性方面效用有限。在认知正常者中，低记忆分数随年龄的增加与淀粉样蛋白阳性随年龄的增加平行，间隔期为10至15年。
尽管低记忆分数是淀粉样蛋白阳性的早期标志物，但其作为无痴呆症人群早期AD筛查指标的价值有限。
