The relationship between neurofilament light chain and depressive symptoms according to cognitive status

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-05-08 DOI:10.1002/trc2.70048

Federico Bellelli, Jeremy Raffin, Davide Angioni, Julie Romana, Maria Soto, Julien Delrieu, Philipe De Souto Barreto, for the MAPT/DSA study group

{"title":"The relationship between neurofilament light chain and depressive symptoms according to cognitive status","authors":"Federico Bellelli, Jeremy Raffin, Davide Angioni, Julie Romana, Maria Soto, Julien Delrieu, Philipe De Souto Barreto, for the MAPT/DSA study group","doi":"10.1002/trc2.70048","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Although recent studies have suggested a positive association between plasma neurofilament light chain (NfL) and depressive symptoms, the moderating effect of cognitive performance on this relationship remains unclear. The aim of this study was to investigate the association between NfL and depressive symptoms in a population of community-dwelling older adults and to determine whether cognitive status could modify this relationship.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 512 individuals (60.2% women) with a median age of 76 years (interquartile range [IQR]: 7) and with available data for plasmatic NfL levels. Depressive symptoms and cognitive status were assessed using the 15-item Geriatric Depression Scale (GDS-15) and the Clinical Dementia Rating (CDR) scale, respectively. Multivariable linear regression analyses were conducted to explore the cross-sectional association between GDS-15 (dependent variable) and plasma NfL levels (pg/mL). The interaction between CDR status (binary: 0 or 0.5) and NfL levels in relation to depressive symptoms was also examined, followed by exploratory simple-slope analyses according to CDR status.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>No significant association was observed between GDS-15 scores and plasma NfL levels (<i>B</i> = 0.002, standard error [SE] = 0.001, <i>p</i> = 0.08) in the entire sample. Although the CDR–NfL interaction was not significant (<i>B</i> = 0.003, SE = 0.002, <i>p</i> = 0.17), exploratory simple-slope analyses revealed that elevated NfL levels were associated with GDS-15 scores (<i>N</i> = 233, <i>B</i> = 0.004, SE = 0.002, <i>p</i> = 0.03) among individuals with a CDR 0.5, but not among those with a CDR 0 (<i>N</i> = 186, <i>p</i> = 0.81).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>NfL levels were not significantly associated with GDS-15 in a population of community-dwelling older adults without dementia. Although no significant CDR–NfL interaction was detected, exploratory analyses suggest that plasma NfL might be associated with GDS-15 scores only among people with a CDR 0.5 (indicative of mild cognitive impairment). Further studies with larger sample sizes are needed to elucidate the potential biological differences in depressive symptoms across different cognitive statuses.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>\n <p>Plasma neurofilament light (NfL) levels might be associated with 15-Geriatric Depression Scale (GDS-15) scores only among people with Clinical Dementia Rating (CDR) 0.5 (indicative of mild cognitive impairment [MCI]), but not among those with CDR 0 (normal cognition).</p>\n </li>\n \n <li>\n <p>Depressive symptoms arising in the context of cognitive impairment may represent a distinct clinical entity compared to those observed in individuals with normal cognitive functioning.</p>\n </li>\n \n <li>\n <p>Further research with larger sample sizes is needed to elucidate potential biological differences in depressive symptoms across varying cognitive statuses (unimpaired cognition, MCI, and dementia).</p>\n </li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70048","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70048","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

INTRODUCTION

Although recent studies have suggested a positive association between plasma neurofilament light chain (NfL) and depressive symptoms, the moderating effect of cognitive performance on this relationship remains unclear. The aim of this study was to investigate the association between NfL and depressive symptoms in a population of community-dwelling older adults and to determine whether cognitive status could modify this relationship.

METHODS

This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 512 individuals (60.2% women) with a median age of 76 years (interquartile range [IQR]: 7) and with available data for plasmatic NfL levels. Depressive symptoms and cognitive status were assessed using the 15-item Geriatric Depression Scale (GDS-15) and the Clinical Dementia Rating (CDR) scale, respectively. Multivariable linear regression analyses were conducted to explore the cross-sectional association between GDS-15 (dependent variable) and plasma NfL levels (pg/mL). The interaction between CDR status (binary: 0 or 0.5) and NfL levels in relation to depressive symptoms was also examined, followed by exploratory simple-slope analyses according to CDR status.

RESULTS

No significant association was observed between GDS-15 scores and plasma NfL levels (B = 0.002, standard error [SE] = 0.001, p = 0.08) in the entire sample. Although the CDR–NfL interaction was not significant (B = 0.003, SE = 0.002, p = 0.17), exploratory simple-slope analyses revealed that elevated NfL levels were associated with GDS-15 scores (N = 233, B = 0.004, SE = 0.002, p = 0.03) among individuals with a CDR 0.5, but not among those with a CDR 0 (N = 186, p = 0.81).

DISCUSSION

NfL levels were not significantly associated with GDS-15 in a population of community-dwelling older adults without dementia. Although no significant CDR–NfL interaction was detected, exploratory analyses suggest that plasma NfL might be associated with GDS-15 scores only among people with a CDR 0.5 (indicative of mild cognitive impairment). Further studies with larger sample sizes are needed to elucidate the potential biological differences in depressive symptoms across different cognitive statuses.

Highlights

Plasma neurofilament light (NfL) levels might be associated with 15-Geriatric Depression Scale (GDS-15) scores only among people with Clinical Dementia Rating (CDR) 0.5 (indicative of mild cognitive impairment [MCI]), but not among those with CDR 0 (normal cognition).
Depressive symptoms arising in the context of cognitive impairment may represent a distinct clinical entity compared to those observed in individuals with normal cognitive functioning.
Further research with larger sample sizes is needed to elucidate potential biological differences in depressive symptoms across varying cognitive statuses (unimpaired cognition, MCI, and dementia).

Abstract Image

查看原文本刊更多论文

认知状态下神经丝轻链与抑郁症状的关系

虽然最近的研究表明血浆神经丝轻链（NfL）与抑郁症状之间存在正相关，但认知表现在这一关系中的调节作用尚不清楚。本研究的目的是在社区居住的老年人中调查NfL与抑郁症状之间的关系，并确定认知状态是否可以改变这种关系。方法：这是对多域阿尔茨海默病预防试验（MAPT）的二次分析，包括512名个体（60.2%为女性），中位年龄为76岁（四分位间距[IQR]: 7），并提供血浆NfL水平的可用数据。抑郁症状和认知状态分别采用15项老年抑郁量表（GDS-15）和临床痴呆评分（CDR）量表进行评估。采用多变量线性回归分析探讨GDS-15（因变量）与血浆NfL水平（pg/mL）的横断面相关性。CDR状态（二值值：0或0.5）与NfL水平与抑郁症状之间的相互作用也被检查，随后根据CDR状态进行探索性单斜率分析。结果在整个样本中，GDS-15评分与血浆NfL水平无显著相关性（B = 0.002，标准误差[SE] = 0.001, p = 0.08）。虽然CDR - NfL相互作用不显著（B = 0.003, SE = 0.002, p = 0.17），但探索性单斜率分析显示，在CDR为0.5的个体中，NfL水平升高与GDS-15评分相关（N = 233, B = 0.004, SE = 0.002, p = 0.03），而在CDR为0的个体中则无关（N = 186, p = 0.81）。在无痴呆的社区老年人中，NfL水平与GDS-15无显著相关。虽然没有发现显著的CDR - NfL相互作用，但探索性分析表明血浆NfL可能仅在CDR为0.5（表明轻度认知障碍）的人群中与GDS-15评分相关。需要进一步的更大样本量的研究来阐明不同认知状态下抑郁症状的潜在生物学差异。血浆神经丝光（NfL）水平可能仅在临床痴呆评分（CDR） 0.5（轻度认知障碍[MCI]）的人群中与15-老年抑郁量表（GDS-15）评分相关，而与CDR 0（正常认知）的人群无关。与在认知功能正常的个体中观察到的抑郁症状相比，在认知障碍的背景下出现的抑郁症状可能代表一种不同的临床实体。需要更大样本量的进一步研究来阐明不同认知状态（未受损认知、轻度认知障碍和痴呆）抑郁症状的潜在生物学差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.