Circulating Amyloid-β and Methionine-Related Metabolites to Predict the Risk of Mild Cognitive Impairment: A Nested
Jingzhu Fu1,2, Yun Zhu3,2, Yue Sun1,2
1Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.
Background:
The high cost, limited availability, and perceived invasiveness of amyloid PET and cerebrospinal fluid biomarkers limit their use for the diagnosis of Alzheimer's disease.
Objective:
The present study aimed to assess the associations of mild cognitive impairment (MCI) with circulating amyloid-β (Aβ), methionine circulating metabolites (MCMs), and their downstream products, and to develop a nomogram based on these easily accessible blood indexes for the individualized prediction of MCI risk in older adults.
Methods:
In this nested case-control study, we recruited 74 MCI patients and, for each, 3 matched controls (n = 222) within the context of the Tianjin Elderly Nutrition and Cognition (TENC) cohort, a population-based prospective study in China. Concentrations of Aβ, MCMs, and their circulating downstream factors (i.e., leukocyte telomere length and inflammatory cytokines) were evaluated in fasting blood sample using standard procedures. We constructed a nomogram for MCI harnessed multivariable logistic models incorporating variables selected in the Lasso regression.
Results:
Among the many biomarkers examined, the final prediction nomogram retained only 3 factors: Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio. The model achieved favorable discrimination, with a C-statistic of 0.75 (95% confidence interval 0.69-0.81) in internal validation after adjustment of optimism. The calibration accuracy was satisfactory; the Brier score of the model was 0.161 in internal validation after adjustment of optimism.
Conclusion:
his study presents an individualized prediction nomogram incorporating only three blood biomarkers (i.e., Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio), which can be conveniently utilized to facilitate early identification and the development of high-risk prevention strategies for MCI in older adults.
Insights
This study developed a simple blood test to predict mild cognitive impairment (MCI) risk in older adults. The nomogram uses amyloid-beta ratio, homocysteine, and SAM/SAH ratio for early MCI identification.
Area of Science:
- Gerontology
- Neurology
- Biomarker Discovery
Background:
- Amyloid PET and CSF biomarkers for Alzheimer's diagnosis are costly and invasive.
- There is a need for accessible, non-invasive biomarkers for early disease detection.
Purpose of the Study:
- To assess associations between mild cognitive impairment (MCI) and circulating amyloid-beta (Aβ), methionine circulating metabolites (MCMs), and their downstream products.
- To develop a predictive nomogram for MCI risk in older adults using easily accessible blood biomarkers.
Main Methods:
- A nested case-control study within the Tianjin Elderly Nutrition and Cognition (TENC) cohort.
- Measured Aβ, MCMs, leukocyte telomere length, and inflammatory cytokines in blood samples.
- Constructed a nomogram using multivariable logistic models and Lasso regression.
Main Results:
- A prediction nomogram was developed using Aβ42/Aβ40 ratio, homocysteine (Hcy), and SAM/SAH ratio.
- The model demonstrated favorable discrimination (C-statistic = 0.75) and satisfactory calibration (Brier score = 0.161).
Conclusions:
- An individualized prediction nomogram using three blood biomarkers (Aβ42/Aβ40 ratio, Hcy, SAM/SAH ratio) was developed.
- This nomogram facilitates convenient early identification of MCI risk in older adults.
- The findings support the development of high-risk prevention strategies for MCI.
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