Fig. 3

Associations between baseline plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, or WMH volumes: stratified by the status of Aβ and cardiometabolic risk factors. Data show how the associations between plasma NfL and longitudinal changes in ADAS-Cog scores (left panel), hippocampal volumes (middle panel), and WMH volumes (right panel) were affected by the Aβ or cardiometabolic risk factors. A Aβ significantly moderated the association between plasma NfL and longitudinal ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004), not WMH volumes (p-value 0.160). Specifically, while higher baseline plasma NfL levels were associated with faster increases in ADAS-Cog scores and decreases in hippocampal volumes, the magnitude of these changes in slopes was more pronounced in Aβ ( +) status compared to Aβ ( −) status. B Similarly, hypertension significantly moderated the association between plasma NfL and longitudinal changes in all outcome variables (all p-values < 0.001). C DM significantly affected the association between plasma NfL and longitudinal ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. D Impaired kidney function did not affect the association between plasma NfL and any outcome variables (all p-values > 0.05). E Obesity significantly moderated the association between plasma NfL and longitudinal hippocampal volumes (p-value 0.026) without affecting ADAS-Cog scores (p-value 0.112) and WMH volumes (p-value 0.058). Of outcome variables, ADAS-Cog score and WMH volume were square root transformed due to non-normal distribution. Continuous variables, including plasma NfL level and outcome variables, were standardized to z-scores. The plotted lines represent estimated z-scores of ADAS-Cog scores, hippocampal volumes, or WMH volumes over time under the condition of baseline plasma NfL at mean -1SD, mean, and mean + 1SD. Interaction p-values were calculated to identify the significance of the three-way interaction term including baseline NfL, time, and the variable of interest (Aβ, hypertension, DM, impaired kidney function, or obesity). Abbreviations: Aβ, amyloid-β; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive subscale; DM, diabetes mellitus; NfL, neurofilament light chain; SD, standard deviation; WMH, white matter hyperintensity