Bellelli Federico, Raffin Jeremy, Angioni Davide, Romana Julie, Soto Maria, Delrieu Julien, Barreto Philipe De Souto
Institut du Vieillissement Gérontopôle de Toulouse Centre Hospitalo-Universitaire de Toulouse Toulouse France.
Fellowship in Geriatric and Gerontology University of Milan Milan Italy.
Alzheimers Dement (N Y). 2025 May 8;11(2):e70048. doi: 10.1002/trc2.70048. eCollection 2025 Apr-Jun.
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.
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.
No significant association was observed between GDS-15 scores and plasma NfL levels ( = 0.002, standard error [SE] = 0.001, = 0.08) in the entire sample. Although the CDR-NfL interaction was not significant ( = 0.003, SE = 0.002, = 0.17), exploratory simple-slope analyses revealed that elevated NfL levels were associated with GDS-15 scores ( = 233, = 0.004, SE = 0.002, = 0.03) among individuals with a CDR 0.5, but not among those with a CDR 0 ( = 186, = 0.81).
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.
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).
尽管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，但认知表现对这种关系的调节作用仍不清楚。本研究的目的是调查社区居住的老年人中NfL与抑郁症状之间的关联，并确定认知状态是否会改变这种关系。
这是对多领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），且有血浆NfL水平的可用数据。分别使用15项老年抑郁量表（GDS-15）和临床痴呆评定量表（CDR）评估抑郁症状和认知状态。进行多变量线性回归分析以探索GDS-15（因变量）与血浆NfL水平（pg/mL）之间的横断面关联。还检查了CDR状态（二分法：0或0.5）与NfL水平在抑郁症状方面的相互作用，随后根据CDR状态进行探索性简单斜率分析。
在整个样本中，未观察到GDS-15评分与血浆NfL水平之间存在显著关联（β = 0.002，标准误[SE] = 0.001，P = 0.08）。尽管CDR-NfL相互作用不显著（β = 0.003，SE = 0.002，P = 0.17），但探索性简单斜率分析显示，在CDR为0.5的个体中，NfL水平升高与GDS-15评分相关（β = 233，P = 0.004，SE = 0.002，P = 0.03），而在CDR为0（正常认知）的个体中则不然（β = 186，P = 0.81）。
在无痴呆的社区居住老年人中，NfL水平与GDS-15无显著关联。尽管未检测到显著的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。需要更大样本量的进一步研究来阐明不同认知状态下抑郁症状的潜在生物学差异。
血浆神经丝轻链（NfL）水平可能仅在临床痴呆评定量表（CDR）为0.5（表明轻度认知障碍[MCI]）的人群中与15项老年抑郁量表（GDS-15）评分相关，而在CDR为0（正常认知）的人群中则不然。与认知功能正常的个体中观察到的抑郁症状相比，认知障碍背景下出现的抑郁症状可能代表一种独特的临床实体。需要更大样本量的进一步研究来阐明不同认知状态（认知未受损、MCI和痴呆）下抑郁症状的潜在生物学差异。
