Plasma neurofilament light chain and risk of death and stroke in community-dwelling elderly individuals

Circulating neuroinjury biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have emerged as indicators of brain health. While NFL predicts stroke in patients with atrial fibrillation, its prognostic value in unselected elderly populations is uncertain. We investigated the associations of NFL and GFAP with cardiovascular events and death in community-dwelling older adults.

Baseline plasma NFL and GFAP concentrations were determined using high-sensitivity Simoa® assays in 806 participants aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Cox regression models with sequential adjustment for demographics, comorbidities, renal function, and NT-proBNP assessed associations with ischaemic stroke, myocardial infarction, cardiovascular death, all-cause death, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, and all-cause death). During a median follow-up of 10 years, 55 ischaemic strokes, 48 myocardial infarctions, 52 cardiovascular deaths, and 188 all-cause deaths occurred. Neurofilament light chain was not independently associated with ischaemic stroke or myocardial infarction and showed no independent association with cardiovascular death after adjustment including NT-proBNP. In contrast, higher NFL was independently associated with all-cause death (adjusted hazard ratio per doubling 1.91; 95% CI 1.49–2.46) and MACE (1.53; 95% CI 1.21–1.93), and improved discrimination for all-cause death beyond established risk factors. Glial fibrillary acidic protein was not associated with any outcome.

In community-dwelling elderly individuals, higher NFL was associated with increased risk of death but not with specific cardiovascular events. These findings suggest that NFL reflects overall physiological vulnerability rather than discrete vascular risk.