Background:Cognitive dispersion, variation in performance across cognitive domains, is posited as a non-invasive and cost-effective marker of early neurodegeneration. Little work has explored associations between cognitive dispersion and Alzheimer’s disease (AD) biomarkers in healthy older adults.Even less is known about the influence or interaction of biomarkers reflecting brain pathophysiology or other risk factors on cognitive dispersion scores. Objective:The main aim of this study was to examine whether higher cognitive dispersion was associated with cerebrospinal fluid (CSF) levels of amyloid-β (Aβ 42), total tau (t-tau), phosphorylated tau (p-tau), and amyloid positivity in a cohort of older adults at various severities of AD. A secondary aim was to explore which AD risk factors were associated with cognitive dispersion scores. Methods:Linear and logistic regression analyses explored the associations between dispersion and CSF levels of Aβ 42, t-tau, and p-tau and amyloid positivity (Aβ 42 < 1000 pg/ml). Relationships between sociodemographics, APOE ɛ4 status, family history of dementia, and levels of depression and dispersion were also assessed. Results:Dispersion did not emerge as associated with any of the analytes nor amyloid positivity. Older (β= –0.007, SE = 0.002, p = 0.001) and less educated (β= –0.009, SE = 0.003, p = 0.009) individuals showed greater dispersion. Conclusion:Dispersion was not associated with AD pathology, but was associated with age and years of education, highlighting individual differences in cognitive aging. The use of this metric as a screening tool for existing AD pathology is not supported by our analyses. Follow-up work will determine if dispersion scores can predict changes in biomarker levels and/or positivity status longitudinally.

中文翻译：

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认知分散与阿尔茨海默病的脑脊液生物标志物无关：欧洲预防阿尔茨海默病 (EPAD) v500.0 队列的结果。

背景：认知分散，即跨认知领域的表现差异，被认为是早期神经退行性疾病的一种非侵入性且具有成本效益的标志物。很少有研究探索健康老年人中认知分散与阿尔茨海默病 (AD) 生物标志物之间的关联。对反映大脑病理生理学或其他风险因素对认知分散评分的生物标志物的影响或相互作用知之甚少。目的：本研究的主要目的是检查较高的认知分散是否与脑脊液 (CSF) 的淀粉样蛋白 β (Aβ 42)、总 tau (t-tau)、磷酸化 tau (p-tau) 和一组不同严重程度 AD 的老年人的淀粉样蛋白阳性。次要目的是探索哪些 AD 风险因素与认知分散评分相关。方法：线性和逻辑回归分析探讨了 Aβ 42、t-tau 和 p-tau 的分散与 CSF 水平与淀粉样蛋白阳性（Aβ 42 < 1000 pg/ml）之间的关联。还评估了社会人口统计学、APOE ɛ4 状态、痴呆家族史以及抑郁和分散程度之间的关系。结果：分散不与任何分析物或淀粉样蛋白阳性相关。年龄较大（β= –0.007，SE = 0.002，p = 0.001）和受教育程度较低（β= –0.009，SE = 0.003，p = 0.009）的个体表现出更大的分散性。结论：离散与 AD 病理无关，但与年龄和受教育年限有关，突出了认知衰老的个体差异。我们的分析不支持将该指标用作现有 AD 病理的筛选工具。