Plasma NfL, P-tau181, and P-tau181/Aβ42 Ratio in Predicting Mild Behavioral Impairment in Dementia-Free Multiethnic Asian Older Adults With Mixed Pathology in a 5-Year Clinical Cohort

• DOI: 10.4088/jcp.24m15558
• Publication Date: 2025-03-04T14:47:18Z
• Authors: Yingqi Liao; Joyce R. Chong; Cheuk Ni Kan; Xuhao Zhao; Yuek Ling Chai; Saima Hilal; Mitchell K. P. Lai; Christopher P. Chen; Xin Xu

Objective: The underlying mechanisms of mild behavioral impairment (MBI), a marker for cognitive and dementia, have remained unclear especially in multiethnic Asian population. study aimed to examine whether baseline Alzheimer disease biomarkers, including plasma neurofilament light (NfL) chain, phosphorylated tau-181 (p-tau181), the p-tau181-to-amyloid-β42 (p-tau181/Aβ42) ratio, could predict MBI incidence dementia-free older adults. Methods: Participants were recruited from community memory clinics August 2010 April 2022. All participants underwent cognitive, neuropsychiatric, clinical assessments annually neuroimaging scans biennially at over maximum 5 years. Neuropsychiatric symptoms (NPS) incident examined using Inventory. Plasma NfL, p-tau181, Aβ42 measured single molecule array assays. Neuroimaging measures hippocampal volume (HV) white matter hyperintensities (WMH) obtained. Results: A total 305 included (age 72.1 ± 7.8 years, 52.5% female, 27.9% no impairment). Among 248 MBI-free baseline, 55 (25.3%) developed Higher p-tau181/Aβ42 NfL predictive increased NPS severity longitudinally (P < .05). p-tau181 levels (hazard ratio [HR] [95% CI], 2.40 [1.00-5.75], P = .05) independently associated with an likelihood after accounting dementia NfL. This relationship significant when controlling HV WMH (HR 2.69 [1.08-6.70], .03). Conclusions: Our findings highlighted between amyloid burden neuroaxonal degeneration neurobehavioral changes adults mixed pathology.