# Long-term cystatin C trajectories and cognitive decline in diabetes and non-diabetes: evidence from a national Chinese cohort

## TL;DR

This study explores how changes in Cystatin C levels over time relate to cognitive decline in people with and without diabetes in a Chinese cohort.

## Contribution

The study identifies distinct Cystatin C trajectories and their differential impact on cognitive decline risk in diabetic and non-diabetic populations.

## Key findings

- Low Cystatin C levels were linked to lower cognitive decline risk in non-diabetic individuals.
- In older diabetic individuals, low Cystatin C levels were associated with higher cognitive decline risk.
- Cumulative Cystatin C exposure increased cognitive decline risk in non-diabetic and non-hypertensive individuals.

## Abstract

The relationship between Cystatin C levels and cognitive function remains unclear. This study aims to investigate the association between cumulative changes and trajectory patterns of Cystatin C and cognitive decline in diabetes and non-diabetes using a nationally representative cohort.

A total of 3,733 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included. Cumulative exposure was assessed based on repeated measurements from the first and third waves. K-means clustering was used to classify the longitudinal changes of Cystatin C. The long-term effects of Cystatin C on cognitive decline were evaluated, and subgroup analyses were performed in different populations. The mediating roles of glucose and HDL were also analyzed.

During the 3-year follow-up, cognitive decline occurred in 20.4% of the participants. In the non-DM (non-diabetes mellitus) group, cumulative Cystatin C increased the risk of cognitive decline. Compared with maintaining a medium level, maintaining a low level of Cystatin C was associated with a decreased risk of cognitive impairment. Subgroup analysis results showed that, in individuals with diabetes and aged ≥65 years, maintaining a low level of Cystatin C was associated with an increased risk of cognitive decline compared with maintaining a medium level. In non-diabetic individuals aged ≥65 years, cumulative Cystatin C increased the risk of cognitive decline. In non-diabetic and non-hypertensive individuals, maintaining a low level of Cystatin C was associated with a decreased risk of cognitive decline compared with maintaining a medium level.

This study found that maintaining a low level of Cystatin C is associated with a lower risk of cognitive decline in non-diabetic individuals, while in older individuals with diabetes, maintaining a low level of Cystatin C increases the risk of cognitive decline. These findings suggest that the long-term dynamic changes in Cystatin C can serve as a useful indicator for assessing the risk of cognitive decline and highlight the need for differentiated preventive strategies in different populations.