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Metabolic profile association with white matter hyperintensity in patients with mild cognitive impairment
Armin Ariaei1,2, Raziyeh Zamiri3, Amirabbas Ghasemi4
1Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
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.
Insights
Specific metabolite levels are linked to white matter hyperintensity (WMH) in mild cognitive impairment (MCI). Altered amino acid metabolism may increase WMH risk in MCI patients.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Brain vasculopathy, particularly cerebral white matter hyperintensity (WMH), is strongly associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD).
- Understanding the mechanisms underlying WMH in MCI is crucial for early diagnosis and intervention.
- Metabolite profiles offer potential insights into the pathogenesis of WMH.
Purpose of the Study:
- To investigate the association between metabolite profiles and WMH in individuals with MCI.
- To explore potential mechanisms linking altered metabolite levels to WMH development in MCI.
Main Methods:
- Retrospective analysis of metabolite profiles and WMH data from MCI patients in the ADNI database.
- Inclusion of 189 subjects: 67 healthy controls, 112 MCI patients, and 10 AD patients, with three years of follow-up.
- Multivariate logistic regression and mixed model regression, adjusted for age, gender, education, and ADAS-Cog13 scores.
Main Results:
- Several metabolites, including methionine, deoxycholic acid, trimethylamine N-oxide, glutamic acid, alanine, palmitoylethanolamide, and arachidonic acid, showed a positive correlation with WMH.
- Conversely, tyrosine, proline, histidine, and beta-aminobutyric acid exhibited a negative correlation with WMH.
- The relationship between metabolite levels and WMH in the MCI group was found to be complex.
Conclusions:
- Specific metabolite alterations are significantly associated with WMH in MCI.
- A proposed mechanism involves amino acid overconsumption in MCI, leading to decreased serum levels and increased brain accumulation, thereby raising WMH risk.
- These findings highlight the potential of metabolite profiling for understanding WMH pathogenesis in cognitive decline.
