Table 3.
Rates of Change in Normalized Whole-Brain Volume, Hippocampal Volume, and Entorhinal Thickness Measures as a Function of Cerebrospinal Fluid (CSF) Biomarker Measures in Alzheimer Diseasea
| CSF Biomarkerb | Mean (SE) | P Valuec | |
|---|---|---|---|
| Normalized Whole-Brain Volume, Points per Year | |||
| Lower 2 Terciles | Upper Tercile | ||
| VILIP-1 | −0.0048 (0.0017) | −0.0123 (0.0025) | .02d |
| tau | −0.0042 (0.0014) | −0.0092 (0.0018) | .03d |
| p-tau181 | −0.0044 (0.0018) | −0.0113 (0.0022) | .02d |
| Upper 2 Terciles | Lower Tercile | ||
| Aβ42 | −0.0061 (0.0011) | −0.0085 (0.0026) | .40 |
| Hippocampal Volume, mm3 per Year | |||
| Lower 2 Terciles | Upper Tercile | ||
| VILIP-1 | −220.2 (45.3) | −418.3 (76.6) | .03d |
| tau | −209.2 (44.3) | −423.3 (71.6) | .01d |
| p-tau181 | −202.4 (44.7) | −414.1 (67.9) | .02d |
| Upper 2 Terciles | Lower Tercile | ||
| Aβ42 | −236.7 (46.9) | −366.8 (85.1) | .18 |
| Entorhinal Cortical Thickness, mm per Year | |||
| Lower 2 Terciles | Upper Tercile | ||
| VILIP-1 | −0.083 (0.037) | −0.248 (0.051) | .01d |
| tau | −0.091 (0.039) | −0.220 (0.051) | .04d |
| p-tau181 | −0.088 (0.037) | −0.225 (0.051) | .03d |
| Upper 2 Terciles | Lower Tercile | ||
| Aβ42 | −0.124 (0.069) | −0.147 (0.039) | .77 |
Abbreviations: APOE, apolipoprotein E ε4; VILIP-1, visinin-like protein 1.
Mixed linear models were used to estimate rates of change in normalized whole-brain volume, hippocampal volume, and entorhinal thickness measures in Alzheimer disease (Clinical Dementia Rating 0.5) over time as a function of CSF biomarker measures (adjusting for age, sex, imaging system type, and APOE ε4 genotype). In these analyses, CSF biomarkers were examined as categorical variables (dichotomized at the 33rd or 66th percentile) to compare rates of brain atrophy between individuals in the upper tercile vs those in the lower 2 terciles for CSF biomarker measures (or the lower tercile vs the upper 2 terciles for Aβ42).
The 66th percentile cutoff values in the Alzheimer disease cohort were ≥595, ≥550, and ≥92 pg/mL for VILIP-1, tau, and p-tau181, respectively. Cerebrospinal fluid Aβ42 values were dichotomized at the 33rd percentile value of <320pg/mL.
P values reflect whether CSF biomarker measures (dichotomized at the 33rd or 66th percentile value) significantly predict rates of brain atrophy in Alzheimer disease (adjusting for age, sex, imaging system type, and APOE ε4 genotype).
P < .05.