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动脉僵硬度调节神经丝轻链(NfL)与认知之间的联系:点燃研究。

Arterial stiffness moderates the link between NfL and cognition: The IGNITE study.

作者信息

Norling Amani M, Lipsitz Lewis A, Dufour Alyssa B, Travison Thomas G, Sewell Kelsey R, Collins Audrey M, Wan Lu, Grove George, Huang Haiqing, Oberlin Lauren E, Jain Shivangi, Karikari Thomas K, Morris Jill K, Jakicic John M, McAuley Edward, Kramer Arthur F, Hillman Charles H, Vidoni Eric D, Billinger Sandra A, Burns Jeffrey M, Marsland Anna L, Kang Chaeryon, Erickson Kirk I

机构信息

The Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Alzheimers Dement. 2025 Aug;21(8):e70554. doi: 10.1002/alz.70554.

Abstract

INTRODUCTION

Arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and plasma neurofilament light (NfL), markers of vascular and neuroaxonal aging, are linked to cognitive decline. Whether higher cfPWV amplifies the NfL-cognition relationship remains unclear.

METHODS

Cognitively unimpaired older adults (N = 570) were assessed using composite cognitive scores from confirmatory factor analysis. cfPWV was dichotomized at the median. Plasma NfL was quantified on a Single Moleculte Array-High Definition, model X (SIMOA-HD X).

RESULTS

Higher NfL correlated with poorer performance across all cognitive domains (p < 0.05), and higher cfPWV was linked to worse episodic memory, working memory, and processing speed (p < 0.05). NfL× cfPWV interactions were significant for episodic (β = 0.289, p = 0.048) and working memory (β = 0.287, p = 0.025), with stronger NfL-cognition associations in the higher cfPWV group (episodic memory: β = -0.324, p < 0.01; working memory: β = -0.343, p < 0.01).

DISCUSSION

Greater cfPWV amplified the association between NfL-related axonal degeneration and cognitive decline.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT02875301 HIGHLIGHTS: Neurofilament light (NfL) and carotid-femoral pulse wave velocity (cfPWV) each correlate with poorer cognitive function in older adults. Higher cfPWV exacerbates the link between NfL and cognitive deficits. Arterial stiffness may worsen NfL-related cognitive decline. Findings reveal synergy between vascular and neurodegenerative aging markers. Examining NfL or cfPWV alone may miss their synergistic effects on cognition.

摘要

引言

动脉僵硬度(颈股脉搏波速度[cfPWV])和血浆神经丝轻链(NfL)作为血管和神经轴突衰老的标志物,与认知能力下降有关。较高的cfPWV是否会增强NfL与认知之间的关系尚不清楚。

方法

使用验证性因素分析得出的综合认知分数对认知未受损的老年人(N = 570)进行评估。cfPWV以中位数进行二分法划分。血浆NfL在单分子阵列高清X型(SIMOA-HD X)上进行定量。

结果

较高的NfL与所有认知领域的较差表现相关(p < 0.05),较高的cfPWV与较差的情景记忆、工作记忆和处理速度相关(p < 0.05)。NfL×cfPWV相互作用在情景记忆(β = 0.289,p = 0.048)和工作记忆(β = 0.287,p = 0.025)方面具有显著性,在较高cfPWV组中NfL与认知的关联更强(情景记忆:β = -0.324,p < 0.01;工作记忆:β = -0.343,p < 0.01)。

讨论

更高的cfPWV增强了与NfL相关的轴突退变和认知能力下降之间的关联。

试验注册

ClinicalTrials.gov:NCT02875301 要点:神经丝轻链(NfL)和颈股脉搏波速度(cfPWV)各自与老年人较差的认知功能相关。较高的cfPWV会加剧NfL与认知缺陷之间的联系。动脉僵硬度可能会使与NfL相关的认知能力下降恶化。研究结果揭示了血管和神经退行性衰老标志物之间的协同作用。单独检查NfL或cfPWV可能会忽略它们对认知的协同作用。

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