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

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 (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).

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).