Kern S, et al. - Researchers investigated the association of cerebrospinal fluid (CSF) neurofilament light protein (NfL) and neurogranin (Ng) levels with the risk of incident mild cognitive impairment (MCI). In addition, they compared these markers with CSF total (T-tau) or phosphorylated tau (P-tau) for risk of MCI in the general community. Outcomes revealed an association of elevated CSF NfL levels, but not of T-tau, P-tau, or Ng levels, with risk of MCI in a community population.

Methods

• For this work, researchers analyzed 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit.
• Follow up for a median of 3.8 years was done (interquartile range, 2.6-5.4 years).
• They used an in-house sandwich enzyme-linked immunosorbent assay to measure the CSF NfL and Ng levels.
• Automated electrochemiluminescence immunoassays were used to measure the CSF Aβ42, T-tau, and P-tau levels.
• They used Cox proportional hazards models, with age as the timescale, to determine the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index.
• They categorized CSF Aβ42 into tertiles to examine its value as an effect modifier; the bottom tertile was defined as having elevated brain amyloid.
• Risk of MCI was assessed as the main outcome measure.

Results

• Researchers included 648 participants without cognitive impairment; at baseline, the median age was 72.3 years (range, 50.7-95.3 years); 366 (56.5%) were men; 96 (14.8%) developed incident MCI.
• In multivariate models, a 3.1-fold increased risk of MCI was evident in association with the top quartile of CSF NfL compared with the bottom quartile (hazard ratio, 3.13; 95% CI, 1.36-7.18).
• CSF T-tau, P-tau, or Ng was not associated with risk of MCI.
• Aβ42 and CSF NfL displayed no interaction for risk of MCI.