Comparison of baseline characteristics between cognitively normal and mild cognitive impairment and association of white matter hyperintensity trajectories with diagnostic outcomes, cognition, and amyloid-β protein: A longitudinal study

Abstract

Background White matter hyperintensity (WMH) is linked to mild cognitive impairment (MCI) and vascular dementia, but its longitudinal change as an independent risk factor remains unclear. Objective This study aims to compare baseline WMH across diagnostic outcomes, and evaluate how WMH trajectory relates to outcomes, cognition, and amyloid-β (Aβ) deposition. Methods Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) included demographics, medical history, WMH, diagnosis, cognition, and amyloid-PET. A total of 857 participants (372 cognitively normal [CN], 485 MCI) were categorized by diagnostic outcome. Baseline WMH differences were analyzed. WMH trajectories (higher/lower) were used in logistic models to predict outcomes, and in linear models to assess cognitive and Aβ changes, adjusting for age, sex, hypertension, BMI, education level, total brain volume and APOE ε4. Results Baseline WMH was significantly higher in the CN-MCI group compared to the CN-CN group and lower in the MCI-CN group than in the MCI-MCI and MCI-AD dementia groups (p < 0.05). Controlling for covariates, regression models found that CN participants with higher WMH trajectories had higher odds of MCI (OR = 3.710, 95%CI [1.836,7.499], p < 0.001), and that participants with higher WMH trajectories had greater impairments in domains of memory (β=−0.331, 95%CI[−0.454,−0.208], p < 0.001), executive function (β=−0.275, 95%CI[−0.370,−0.179], p < 0.001), and language (β=−0.248, 95%CI[−0.344,−0.152], p < 0.001). In [18F] florbetapir (FBP) tracers, increased Aβ deposition was also observed in higher WMH groups (β = 0.056, 95% CI[0.018,0.095], p = 0.004). Conclusions WMH baseline and trajectory changes are key risk factors for CN cognitive decline. WMH trajectory changes are linked to cognitive function and brain Aβ deposition.