van Gennip April C E, Satizabal Claudia L, Tracy Russell P, Sigurdsson Sigurdur, Gudnason Vilmundur, Launer Lenore J, van Sloten Thomas T
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, The Netherlands.
Geroscience. 2024 Feb;46(1):505-516. doi: 10.1007/s11357-023-00888-1. Epub 2023 Aug 2.
We investigated the associations of plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau (t-tau) with markers of cerebral small vessel disease (SVD) and with incident dementia. We also investigated whether associations of NfL, GFAP, and t-tau with incident dementia were explained by SVD. Data are from a random subsample (n = 1069) of the population-based AGES-Reykjavik Study who underwent brain MRI and in whom plasma NfL, GFAP, and t-tau were measured at baseline (76.1 ± 5.4 years/55.9% women/baseline 2002-2006/follow-up until 2015). A composite SVD burden score was calculated using white matter hyperintensity volume (WMHV), subcortical infarcts, cerebral microbleeds, and large perivascular spaces. Dementia was assessed in a 3-step process and adjudicated by specialists. Higher NfL was associated with a higher SVD burden score. Dementia occurred in 225 (21.0%) individuals. The SVD burden score significantly explained part of the association between NfL and incident dementia. WMHV mostly strongly contributed to the explained effect. GFAP was not associated with the SVD burden score, but was associated with WMHV, and WMHV significantly explained part of the association between GFAP and incident dementia. T-tau was associated with WMHV, but not with incident dementia. In conclusion, the marker most strongly related to SVD is plasma NfL, for which the association with WMHV appeared to explain part of its association with incident dementia. This study suggests that plasma NfL may reflect the contribution of co-morbid vascular disease to dementia. However, the magnitude of the explained effect was relatively small, and further research is required to investigate the clinical implications of this finding.
我们研究了血浆神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）和总tau蛋白（t-tau）与脑小血管病（SVD）标志物及新发痴呆之间的关联。我们还研究了NfL、GFAP和t-tau与新发痴呆之间的关联是否可由SVD来解释。数据来自基于人群的AGES-雷克雅未克研究的随机子样本（n = 1069），这些参与者接受了脑部MRI检查，并在基线时（76.1±5.4岁/55.9%为女性/基线时间为2002 - 2006年/随访至2015年）测量了血浆NfL、GFAP和t-tau。使用白质高信号体积（WMHV）、皮质下梗死、脑微出血和大的血管周围间隙计算了一个综合SVD负担评分。痴呆通过三步法进行评估并由专家判定。较高的NfL与较高的SVD负担评分相关。225名（21.0%）个体发生了痴呆。SVD负担评分显著解释了NfL与新发痴呆之间关联的一部分。WMHV对所解释的效应贡献最大。GFAP与SVD负担评分无关，但与WMHV相关，并且WMHV显著解释了GFAP与新发痴呆之间关联的一部分。T-tau与WMHV相关，但与新发痴呆无关。总之，与SVD最密切相关的标志物是血浆NfL，其与WMHV的关联似乎解释了其与新发痴呆之间关联的一部分。这项研究表明血浆NfL可能反映了合并存在的血管疾病对痴呆的影响。然而，所解释效应的大小相对较小，需要进一步研究来探讨这一发现的临床意义。
