Specifically, measuring biomarkers of neurodegeneration, including glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) protein, and of AD neuropathology, including phosphorylated Tau-181 (pTau-181), and amyloid beta (Aβ40 and Aβ42) in plasma is an efficient and non-invasive method to study the early pathologic risk of cognitive impairment and AD. The gene discussed is NEFL; the disease is Cognitive impairment.