载脂蛋白E-ε4调节认知功能未受损的中年个体中区域淀粉样蛋白沉积与认知表现之间的关联。
APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals.
作者信息
Brugulat-Serrat Anna, Sánchez-Benavides Gonzalo, Cacciaglia Raffaele, Salvadó Gemma, Shekari Mahnaz, Collij Lyduine E, Buckley Christopher, van Berckel Bart N M, Perissinotti Andrés, Niñerola-Baizán Aida, Milà-Alomà Marta, Vilor-Tejedor Natàlia, Operto Grégory, Falcon Carles, Grau-Rivera Oriol, Arenaza-Urquijo Eider M, Minguillón Carolina, Fauria Karine, Molinuevo José Luis, Suárez-Calvet Marc, Gispert Juan Domingo
机构信息
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain.
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
出版信息
EJNMMI Res. 2023 Mar 1;13(1):18. doi: 10.1186/s13550-023-00967-6.
PURPOSE
To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants.
METHODS
The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer's Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume.
RESULTS
In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum.
CONCLUSION
CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer's disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD.
CLINICALTRIALS
gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969 .
目的
确定APOE-ε4等位基因是否会调节中年认知未受损（CU）参与者区域β淀粉样蛋白（Aβ）积累与认知变化之间的关系。
方法
352名CU参与者（平均年龄61.1[4.7]岁）完成了两项认知评估（平均间隔3.34年），接受了[F]氟代甲磺酸Aβ正电子发射断层扫描（PET）、T1加权磁共振成像（MRI）以及APOE基因分型。通过视觉阅读（VR）和区域Centiloids在五个感兴趣区域评估全球和区域Aβ PET阳性。在控制年龄、性别、教育程度、认知基线分数和海马体积后，建立线性回归模型，以检验区域和全球Aβ PET阳性与APOE-ε4状态之间的相互作用对使用临床前阿尔茨海默病认知综合量表（PACC）、情景记忆和执行功能评估的纵向认知变化的影响。
结果
共有57名参与者（16.2%）为VR阳性，其中41名（71.9%）为APOE-ε4携带者。对于任何认知测试，均未发现显著的APOE-ε4*全球Aβ PET相互作用与认知变化相关。然而，颞叶区域（n = 19[9.81%]，p = 0.04）和纹状体（n = 8[4.14%]，p = 0.01）VR阳性的APOE-ε4携带者在PACC上表现出更大幅度的下降。当用Centiloid值确定区域PET阳性时，颞叶区域的结果得到了重复。在区域上，纹状体VR阳性与更高的记忆下降相关。至于执行功能，在颞叶和顶叶区域以及纹状体中发现了APOE-ε4与区域VR阳性之间的相互作用。
结论
在已知在阿尔茨海默病（AD）连续体后期阶段积累淀粉样蛋白的区域中，Aβ PET VR呈阳性的CU APOE-ε4携带者表现出更陡峭的认知下降。这项工作支持了这样的观点，即Aβ PET的区域VR可能传达有关未来患AD风险较高个体未来认知下降的预后信息。
临床试验
gov标识符：NCT02485730。于2015年6月20日注册https://clinicaltrials.gov/ct2/show/NCT02485730 以及ClinicalTrials.gov标识符：NCT02685969。于2016年2月19日注册https://clinicaltrials.gov/ct2/show/NCT02685969 。
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