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Heterogeneity of cerebral atrophic rate in mild cognitive impairment and its interactive association with proteins
Jingyi Tang1, Zhiyu Cao2, Ming Lei1
1Department of Neurology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou City, Guangdong Province, MN 510120, China.
Background:
Heterogeneity of cerebral atrophic rate commonly exists in mild cognitive impairment (MCI), which may be associated with microglia-involved neuropathology and have an influence on cognitive outcomes.
Objective:
We aim to explore the heterogeneity of cerebral atrophic rate among MCI and its association with plasma proteins related to microglia activity, with further investigation of their interaction effects on long-term cognition.
Subjects:
A total of 630 MCI subjects in the ADNI database were included, of which 260 subjects were available with baseline data on plasma proteins.
Methods:
Group-based multi-trajectory modeling (GBMT) was used to identify the latent classes with heterogeneous cerebral atrophic rates. Associations between latent classes and plasma proteins related to microglia activity were investigated with generalized linear models. Linear mixed effect models (LME) were implemented to explore the interaction effects between proteins related to microglia activity and identified latent classes on longitudinal cognitive changes.
Results:
Two latent classes were identified and labeled as the slow-atrophy class and the fast-atrophy class. Associations were found between such heterogeneity of atrophic rates and plasma proteins related to microglia activity, especially AXL receptor tyrosine kinase (AXL), CD40 antigen (CD40), and tumor necrosis factor receptor-like 2 (TNF-R2). Interaction effects on longitudinal cognitive changes showed that higher CD40 was associated with faster cognitive decline in the slow-atrophy class and higher AXL or TNF-R2 was associated with slower cognitive decline in the fast-atrophy class.
Conclusions:
Heterogeneity of atrophic rates at the MCI stage is associated with several plasma proteins related to microglia activity, which show either protective or adverse effects on long-term cognition depending on the variability of atrophic rates.
Insights
Brain atrophy rates vary in mild cognitive impairment (MCI) and link to plasma proteins. These proteins influence long-term cognition, showing protective or adverse effects based on atrophy speed.
Area of Science:
- Neuroscience
- Biomarkers
- Neurology
Background:
- Cerebral atrophy rate heterogeneity is common in mild cognitive impairment (MCI).
- This heterogeneity may involve microglia-related neuropathology.
- It can impact cognitive outcomes in MCI patients.
Purpose of the Study:
- Explore cerebral atrophy rate heterogeneity in MCI.
- Investigate associations with plasma proteins linked to microglia activity.
- Examine interaction effects on long-term cognitive changes.
Main Methods:
- Utilized Group-Based Multi-Trajectory Modeling (GBMT) to identify atrophy rate classes.
- Employed generalized linear models to assess associations with plasma proteins.
- Applied Linear Mixed Effect Models (LME) for interaction effects on cognition.
Main Results:
- Identified two classes: slow-atrophy and fast-atrophy.
- Found associations between atrophy heterogeneity and plasma proteins (AXL, CD40, TNF-R2).
- Observed interaction effects: CD40 linked to faster decline in slow-atrophy; AXL/TNF-R2 to slower decline in fast-atrophy.
Conclusions:
- MCI brain atrophy rate heterogeneity correlates with plasma microglia-related proteins.
- These proteins exert differential effects on long-term cognition.
- Effects depend on the individual's rate of cerebral atrophy.
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