Metabolic Profile Association With White Matter Hyperintensity in Patients With Mild Cognitive Impairment Publisher



Ariaei A ; Zamiri R ; Ghasemi A ; Rezayani B ; Rezayani S ; Ezatpour A ; Farshidi N ; Sheikhi E A ; Roghanian A
Source: IBRO Neuroscience Reports Published:2026

Abstract

Brain vasculopathy, including cerebral white matter hyperintensity (WMH), is highly associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD) pathology. Metabolite levels provide clues to illuminate the mechanism of WMH in MCI. Therefore, the current study investigated the association between metabolite profile and WMH in MCI. Metabolite profiles and WMH data of MCI patients with three consecutive years of follow-up were retrospectively extracted from the ADNI database. Multivariate logistic regression and mixed model regression adjusted for age, gender, education, and ADAS-Cog13 were used to evaluate the association between metabolite levels and WMH. A total number of 189 subjects were included in this study, allocated into three groups of healthy individuals (n = 67), mild cognitive impairment (n = 112), and AD (n = 10). Based on the multivariate logistic regression, methionine, deoxycholic acid, trimethylamine N-oxide, glutamic acid, and alanine, palmitoylethanolamide, and arachidonic acid positively correlated with WMH (OR:4.014 [95% CI: 1.329–12.128]; OR: 1.272 [95% CI: 1.076–1.504]; OR: 1.839 [95% CI: 1.007–1.390]; OR: 8.474 [95% CI: 2.730–26.300]; OR: 3.532 [95% CI: 1.544–8.076]; OR: 2.486 [95% CI: 1.152–5.364]; OR:2.110 [95% CI: 1.003–4.440], respectively), while tyrosine, proline, histidine, and beta-aminobutyric acid negatively correlated with WMH (OR:0.287 [95% CI:0.092–0.894]; OR:0.381 [95% CI:0.162–0.894]; OR:0.240 [95% CI:0.059–0.982]; OR: 0.598 [95% CI: 0.382–0.939], respectively). The association of metabolite levels with WMH in the MCI group is complex. One of the suggested mechanisms is amino acid overconsumption in the MCI group, resulting in decreasing their detected level in the serum while accumulation of their metabolites in the brain increases the risk of WMH. © 2026 The Authors