Figure 3.

Forest plot of the association between baseline WMH volume and cognitive function slopes. (A) The association between baseline WMH volume and ΔMemory. (B) The association between baseline WMH volume and ΔEF. The cognitive function slopes were calculated by using linear mixed-effects models among non-dementia participants with at least one follow-up ADNI_MEM/EF score within the next 48 months (n = 1,056, see Supplementary Table S5). In model 1, baseline WMH volume, plus age, sex, education, APOE ε4 status, and cognitive status were used as predictors of cognitive function slopes. In model 2, hypertension and smoking status were used as additional predictors on the basis of model 1. In model 3, CSF core biomarkers, including Aβ₄₂ and p-tau levels, were used as additional predictors on the basis of model 2. In model 4, the interaction term of CSF Aβ₄₂ and WMH were used as additional predictors on the basis of model 3. The WMH volume was total intracranial volume-normalized and log-transformed. CSF t-tau was not included due to its extremely high correlation with p-tau (R > 0.900, p < 0.001). For effect estimates with exact 95% CI and statistical significance values, see Supplementary Table S9. MCI, mild cognitive impairment; WMH, white matter hyperintensity; CSF, cerebrospinal fluid; Aβ, β-amyloid; p-tau, phosphorylated tau; t-tau, total tau; APOE, apolipoprotein E; MEM, memory sub-domain; EF, executive function; ADNI, Alzheimer’s Disease Neuroimaging Initiative; CI, confidence interval.