Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults

Abstract

Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer's Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β = - 0.007, 95% CI [- 0.013, - 0.001]; CCS: β = - 0.003, 95% CI [- 0.006, - 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β = - 0.003, 95% CI [- 0.005, - 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β = - 0.07, 95% CI [- 0.12, - 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.

Figure 1

Significant findings in mixed-effects models. (a) Correlation between MMSE and NfL in the whole population at the initial level. (b) Correlation between DSST-WAISR and NfL in the whole population at the initial level. (c) Correlation between CCS and NfL in the whole population at the initial level. (d) Correlation between DSST-WAISR and NfL in the MCI group at the initial level. (e) Correlation between CCS and NfL in the MCI group at the initial level. (f) DSST-WAISR comparison between quartile groups in the MCI group at the initial level. (g) CCS comparison between quartile groups in the MCI group at the initial level. (h) CCS trajectory in the MCI group over a 4-year period (standard errors are used as error bars).