Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v₁ (2004-2009) and v₂ (2009-2013) plasma NfL exposure and ancillary sMRI data at v_scan (2011-2015, n = 179, mean v₁ to v_scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL_(v1) was associated with larger WMLV (both Log_e transformed), after 5-6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv₂ was linked to a 125 mm³ lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL_bayes). Among African American adults, NfL_v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.