Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease

INTRODUCTION: Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non‐dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking. METHODS: Associations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. RESULTS: We found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH−) or WMH (cut‐off for log‐transformed WMH volume at 50th percentile; N−WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH−, N−WMH+, and N−WMH− individuals. DISCUSSION: Plasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.