Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
Neurobiol Aging. 2023 Oct;130:124-134. doi: 10.1016/j.neurobiolaging.2023.06.016. Epub 2023 Jun 29.
Spatial cognition is associated with Alzheimer's disease (AD) biomarkers in the symptomatic stages of the disease. We investigated whether cerebrospinal fluid (CSF) biomarkers (phosphorylated-tau [p-tau] and β-amyloid) are associated with poorer spatial cognition in clinically normal older adults. Participants were 1875 clinically normal adults (age 67.8 [8.5] years) from the European Prevention of Alzheimer's Dementia Consortium. Mixed effect models assessed the cross-sectional association between p-tau, β-amyloid (Aβ) and p-tau/Aβ ratio and spatial cognition measured using semi-automated Supermarket Task and the 4 Mountains Task. Levels of p-tau, Aβ and p-tau/Aβ ratio were significantly associated with spatial cognition scores on both tasks. The p-tau/Aβ ratio showed the largest effect sizes (β = -0.04/0.05, p < 0.001). Lower entorhinal cortical volume was associated with poorer outcomes on both tasks (β = 0.06, p < 0.002) and accounted for 18%-22% of the direct association between p-tau and spatial cognition scores. In conclusion, degeneration of the entorhinal cortex mediates a significant proportion of the association between p-tau and spatial assessments in cognitively normal adults. Future studies should focus on increasing the sensitivity of digital spatial assessments.
空间认知与阿尔茨海默病（AD）生物标志物在疾病的有症状阶段有关。我们研究了脑脊液（CSF）生物标志物（磷酸化tau [p-tau]和β-淀粉样蛋白）是否与临床正常的老年人群中较差的空间认知有关。参与者是来自欧洲预防阿尔茨海默病痴呆症联盟的 1875 名临床正常的成年人（年龄 67.8 [8.5]岁）。混合效应模型评估了 p-tau、β-淀粉样蛋白（Aβ）和 p-tau/Aβ 比值与使用半自动超市任务和 4 山任务测量的空间认知之间的横断面关联。在这两项任务中，p-tau、Aβ 和 p-tau/Aβ 比值与空间认知评分显著相关。p-tau/Aβ 比值显示出最大的效应量（β=-0.04/0.05，p<0.001）。内嗅皮层体积较低与这两项任务的表现较差（β=0.06，p<0.002）有关，并且解释了 p-tau 与空间认知评分之间直接关联的 18%-22%。总之，内嗅皮层的退化介导了 p-tau 与认知正常成年人的空间评估之间的显著比例的关联。未来的研究应侧重于提高数字空间评估的敏感性。
