Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse (CHU Toulouse), Toulouse, France.
EA 2114, Département de Psychologie-Psychologie des Ages de la Vie et Adaptation, University of Tours, 3, Rue des Tanneurs, 37041, Tours Cedex 1, France.
J Neurol. 2019 Apr;266(4):835-843. doi: 10.1007/s00415-019-09203-5. Epub 2019 Jan 28.
Observational and interventional studies addressing the link between amyloid (Aβ) burden and cognitive decline are increasing, but a clear definition of amyloid positivity is still lacking. This may represent a great stake for therapeutic studies enrolling Aβ + patients only. The main objective of this study was to define a population with "equivocal" amyloid status, and evaluate their cognitive changes.
Sixty-five participants over 75 years old, from the Control group of the interventional MAPT study, at risk to develop Alzheimer's disease, were included. Participants were classified into three groups in terms of amyloid load: Aβ +, Aβ - and Equivocal participants (according to visual reading, global standardized uptake (SUVR) cut-offs, or a k-mean clustering method). The cognitive changes over time (memory, executive functions, attention and processing speed) of this Equivocal group were then compared to Aβ + and Aβ - participants.
When classified by visual read, Equivocal participants' memory scores were comparable to the Aβ- participants, and greater than in Aβ + participants over time. Secondary analyses, using SUVR cut-offs classification, showed different trajectories with Equivocal participants being comparable to the Aβ + participants, and lower than Aβ-, on executive performance over time.
This original work pointed out a population that may be of great interest for interventional studies, raising the question of how amyloid status should be defined and integrated in such studies. These findings should be replicated in future studies on larger datasets, to confirm what methodological approach would be the most suitable to highlight this specific neuroimaging entity.
越来越多的观察性和干预性研究探讨了淀粉样蛋白（Aβ）负担与认知能力下降之间的关系，但仍缺乏明确的淀粉样蛋白阳性定义。这对于仅招募 Aβ+患者的治疗性研究来说可能是一个巨大的挑战。本研究的主要目的是定义一个具有“不确定”淀粉样蛋白状态的人群，并评估其认知变化。
我们纳入了 65 名年龄在 75 岁以上、来自干预性 MAPT 研究对照组、有发展为阿尔茨海默病风险的参与者。根据淀粉样蛋白负荷将参与者分为三组：Aβ+、Aβ-和不确定组（根据视觉阅读、全局标准化摄取值比（SUVR）截断值或 k-均值聚类方法）。然后比较这个不确定组的认知变化（记忆、执行功能、注意力和处理速度）与 Aβ+和 Aβ-组。
当根据视觉阅读分类时，不确定组的记忆评分与 Aβ-组相当，且随着时间的推移，优于 Aβ+组。使用 SUVR 截断值分类的二次分析显示，随着时间的推移，不确定组与 Aβ+组的执行功能轨迹不同，且低于 Aβ-组。
这项原创工作指出了一个可能对干预性研究有很大兴趣的人群，提出了应该如何定义淀粉样蛋白状态并将其纳入此类研究的问题。这些发现应在未来的研究中使用更大的数据集进行复制，以确认哪种方法最适合突出这种特定的神经影像学实体。
