Abstract

Background:

Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established.

Objective:

In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance.

Methods:

309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline.

Results:

pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline.

Conclusion:

pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.

中文翻译：

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1Florida 阿尔茨海默病研究中心 (ADRC) 中血浆神经丝光的效用

摘要

背景：

血浆 NfL (pNfL) 水平在许多神经系统疾病中升高。然而，pNfL 在临床环境中的效用尚未确定。

客观的：

在一组不同的老年参与者中，我们检查了：1）pNfL 与年龄、性别、西班牙裔、诊断以及结构和淀粉样蛋白成像生物标志物的关联；2）它与基线和纵向认知和功能表现的关联。

方法：

309 名受试者在基线时被分类为认知正常 (CN) 或认知障碍。大多数受试者进行了结构 MRI 和淀粉样蛋白 PET 扫描。最常见的病因诊断是阿尔茨海默病 (AD)，但也有其他神经和神经精神疾病。我们评估了 pNfL 与认知和功能状态、原发性病因、成像生物标志物以及认知和功能衰退的关系。

结果：

pNfL 随着年龄、海马萎缩程度和淀粉样蛋白负荷的增加而增加，并且在 CN 受试者中的女性中更高，但与西班牙裔无关。与 CN 受试者相比，AD 或 FTLD 患者的 pNfL 升高，但神经精神或其他疾病患者的 pNfL 升高。海马萎缩、淀粉样蛋白阳性和更高的 pNfL 水平各自增加了预测基线 CDR-SB 更大功能障碍的独特差异。在考虑到基线时的海马萎缩和记忆评分后，较高的基线 pNfL 水平也预示着更大的认知和功能下降。

结论：

pNfL 可能对记忆障碍评估中的脑成像和认知测试具有补充和支持作用，尽管其作为独立测量的诊断敏感性和特异性是适度的。在没有昂贵的神经影像学检查的情况下，pNfL 可用于区分神经退行性疾病和神经精神疾病。