性别和教育程度会改变主观认知衰退与淀粉样蛋白病理学之间的关联。

Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology.

作者信息

Bolton Corey J, Khan Omair A, Liu Dandan, Wilhoite Sydney, Dumitrescu Logan, Peterson Amalia, Blennow Kaj, Zetterberg Henrik, Hohman Timothy J, Jefferson Angela L, Gifford Katherine A

出版信息

medRxiv. 2023 Nov 4:2023.11.03.23297795. doi: 10.1101/2023.11.03.23297795.

DOI:10.1101/2023.11.03.23297795

PMID:37961115

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10635270/

Abstract

BACKGROUND

Subjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer's disease (AD) biomarkers in non-demented older adults.

METHOD

Vanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=156, 72±6 years, 37% mild cognitive impairment, 33% female) completed fasting lumbar puncture, SCD assessment, and Wide Range Achievement Test-III Reading subtest to assess reading level at baseline as a a proxy for educational quality. Cerebrospinal fluid (CSF) biomarkers for AD (β-amyloid (Aβ42), Aβ42/40 ratio, phosphorylated tau (p-tau), tau, and neurofilament light (NfL)) were analyzed in batch. Linear mixed effects models related SCD to CSF AD biomarkers and follow-up models assessed , and interactions on AD biomarkers.

RESULT

In main effect models, higher SCD was associated with lower Aβ42 and Aβ42/40 ratio (p-values<0.004). SCD was not associated with tau, p-tau, or NfL levels ( values>0.38). SCD score interacted with sex on Aβ42/40 ratio ( =0.03) but no other biomarkers ( -values>0.10). In stratified models, higher SCD was associated with lower Aβ42/40 ratio in men ( =0.0003) but not in women ( =0.48). SCD score interacted with education on Aβ42 ( =0.005) and Aβ42/40 ratio ( =0.001) such that higher education was associated with a stronger negative association between SCD and amyloid levels. No interaction was found (p-values> 0.51) though significant associations between SCD and amyloid markers were seen in the higher reading level group (p-values<0.004) but not the lower reading level group (p-values>0.12) when stratified by a median split in reading level.

CONCLUSION

Among community-dwelling older adults free of clinical dementia, higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD-related brain changes in men and individuals with higher quantity and quality of education. SCD was not associated with CSF markers of tau pathology or neurodegeneration. These findings suggest that considering sex and education is important when assessing SCD in older adults.

摘要

背景

主观认知衰退（SCD）可能是痴呆症的早期风险因素，在高学历人群和女性中尤为如此。本研究探讨了教育程度和性别对非痴呆老年人中SCD与阿尔茨海默病（AD）生物标志物之间关联的影响。

方法

范德比尔特记忆与衰老项目的参与者，无临床痴呆或中风（n = 156，72±6岁，37%为轻度认知障碍，33%为女性），在基线时完成空腹腰椎穿刺、SCD评估以及广泛成就测验第三版阅读子测验以评估阅读水平，作为教育质量的替代指标。对脑脊液（CSF）中AD的生物标志物（β-淀粉样蛋白（Aβ42）、Aβ42/40比值、磷酸化tau蛋白（p-tau）、tau蛋白和神经丝轻链（NfL））进行批量分析。线性混合效应模型将SCD与CSF AD生物标志物相关联，后续模型评估性别和教育程度对AD生物标志物的交互作用。

结果

在主效应模型中，较高的SCD与较低的Aβ42和Aβ42/40比值相关（p值<0.004）。SCD与tau蛋白、p-tau蛋白或NfL水平无关（p值>0.38）。SCD评分与性别在Aβ42/40比值上存在交互作用（p = 0.03），但与其他生物标志物无交互作用（p值>0.10）。在分层模型中，较高SCD与男性较低的Aβ42/40比值相关（p = 0.0003），而与女性无关（p = 0.48）。SCD评分与教育程度在Aβ42（p = 0.005）和Aβ42/40比值（p = 0.001）上存在交互作用，即较高的教育程度与SCD和淀粉样蛋白水平之间更强的负相关有关。未发现性别与教育程度的交互作用（p值>0.51），尽管按阅读水平中位数分割分层时，在较高阅读水平组中可见SCD与淀粉样蛋白标志物之间存在显著关联（p值<0.004），而在较低阅读水平组中未发现（p值>0.12）。

结论

在无临床痴呆的社区居住老年人中，较高的SCD与更大程度的脑淀粉样蛋白积累相关，这是AD最早的病理变化之一。SCD在检测男性以及教育数量和质量较高的个体中与AD相关的早期脑变化时似乎最有用。SCD与tau蛋白病理学或神经退行性变的CSF标志物无关。这些发现表明，在评估老年人的SCD时，考虑性别和教育程度很重要。