Table 2. Variables Associated With Longitudinal Plasma Neurofilament Light Measuresa.
Measure | Continuous Variables | Dichotomous Variablesb | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline NfL Level | NfL Rate | R2 | Baseline NfL Level | NfL Rate | R2 | |||||
β | P Valuec | β | P Valuec | β | P Valuec | β | P Valuec | |||
Aβ42 level | −3.11 | <.001 (<.001) | −0.64 | <.001 (.001) | 0.22 | 5.35 | <.001 (<.001) | 0.98 | .007 (.01) | 0.21 |
t-tau Level | 2.99 | <.001 (<.001) | 0.49 | .01 (.02) | 0.21 | 5.29 | <.001 (<.001) | 1.25 | .001 (.004) | 0.21 |
p-tau Level | 2.70 | <.001 (.002) | 0.52 | .009 (.02) | 0.21 | 5.34 | <.001 (<.001) | 1.37 | <.001 (.003) | 0.21 |
Hippocampus volume | −4.56 | <.001 (<.001) | −0.74 | <.001 (<.001) | 0.26 | 7.66 | <.001 (<.001) | 1.22 | <.001 (.001) | 0.24 |
Entorhinal cortex | −3.79 | <.001 (<.001) | −0.78 | .001 (.002) | 0.23 | 5.81 | <.001 (<.001) | 1.05 | .006 (.01) | 0.22 |
Temporal composite | −4.35 | <.001 (<.001) | −0.62 | .005 (.009) | 0.24 | 7.75 | <.001 (<.001) | 0.86 | .04 (.06) | 0.23 |
Ventricular volume | 3.55 | <.001 (<.001) | 0.55 | <.001 (.002) | 0.22 | 3.90 | .002 (.006) | 0.60 | .06 (.08) | 0.20 |
FDG-PET composite | −3.79 | <.001 (<.001) | −0.51 | .008 (.01) | 0.23 | 6.78 | <.001 (<.001) | 1.01 | .004 (.01) | 0.24 |
White matter lesions | 0.99 | .11 (.15) | 0.36 | .09 (.10) | 0.18 | 2.28 | .13 (.15) | 1.18 | .02 (.03) | 0.19 |
MMSE score | −4.35 | <.001 (<.001) | −0.4 | .04 (.04) | 0.22 | 10.38 | <.001 (<.001) | 0.95 | .07 (.08) | 0.22 |
CDR-SB score | 4.46 | <.001 (<.001) | 0.65 | .002 (.004) | 0.22 | 22 | <.001 (<.001) | 1.47 | .78 (.78) | 0.21 |
ADAS-Cog score | 4.59 | <.001 (<.001) | 0.74 | <.001 (<.0001) | 0.24 | 17.79 | <.001 (<.001) | 4.65 | .23 (.25) | 0.23 |
Abbreviations: Aβ, amyloid β; ADAS-Cog, Alzheimer Disease Assessment Scale-Cognitive Subscale; CDR-SB, Clinical Dementia Rating Scale Sum of Boxes; CSF, cerebrospinal fluid; FDG-PET, fluorodeoxyglucose-positron emission tomography; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; NfL, neurofilament light; p-tau, phosphorylated tau; and t-tau, total tau.
Variables associated with longitudinal NfL measures were tested in linear mixed-effects models adjusted for age and sex. All predictors were scaled to have zero mean and unit variance so that effect sizes are directly comparable with the additional change in NfL levels per year (or additional baseline NfL levels) expected with a 1-SD increase in the variable’s value. For dichotomous variables, normal is always represented as zero and pathological as 1; therefore, all dichotomous coefficients are positive, indicating the effect of being pathological for the given measure.
Cut points were a priori (CSF) or 90% sensitivity for Alzheimer disease (MRI and cognition).
P values in parentheses are corrected for multiple comparisons using the Benjamini-Hochberg procedure.