High blood glucose accelerates cognitive decline in stroke survivors

High blood glucose levels in stroke survivors are associated with faster cognitive decline, according to an NIA-funded study. In contrast, the researchers found no evidence that post-stroke LDL cholesterol or high blood pressure levels accelerate cognitive decline. These findings, published in JAMA Network Open, suggest that glucose management in stroke survivors may help preserve cognition after stroke.

Previous research has shown that stroke accelerates cognitive decline and stroke survivors are up to 50 times more likely to develop dementia. Elevated blood pressure, glucose (blood sugar), and low-density lipoprotein (LDL) cholesterol levels are known risk factors for stroke and are also associated with cognitive decline in stroke-free adults. In this study, a scientific team led by researchers at the University of Michigan examined whether these modifiable risk factors, meaning they can be controlled or changed, are associated with faster cognitive decline in stroke survivors.

First, the researchers looked at health data collected over several years from four U.S. population studies and identified 982 stroke survivors ranging from age 44 to 96. The data set included information on cognitive function before and after stroke, along with post-stroke measures of blood pressure, LDL cholesterol, and glucose. Based on this data, the researchers developed multiple statistical models to estimate the individual and combined effects of post-stroke blood pressure, LDL cholesterol, and glucose levels on cognitive function over time.

Cognitive function declined over time in all the stroke survivors. However, higher post-stroke glucose levels — but not LDL cholesterol or blood pressure levels — were associated with faster overall cognitive decline. Specifically, the estimated difference in overall cognitive function between stroke survivors with the highest and lowest glucose levels at 12 years was 5% faster. This is roughly equivalent to aging 1.6 years faster for every 10 mg/dL increase in glucose levels in stroke survivors.

Interestingly, post-stroke declines in memory and executive function, which is the ability to plan ahead and meet goals, were not accelerated by high glucose levels. This suggests that different parts of the post-stroke brain may be more vulnerable to the effects of high glucose.

Since high glucose levels increase the risk for dementia, the study team explored whether APOE-ɛ4, a gene associated with Alzheimer’s disease, changes the effect of high glucose on post-stroke cognitive decline. Analyzing available genetic data for a subgroup of the stroke survivors, they found that it did not. This suggests that glucose-associated cognitive decline operates through different cellular pathways than Alzheimer’s, such as those linked to vascular disease.

This study presents new evidence that high glucose, but not LDL cholesterol or blood pressure, accelerates the cognitive decline in stroke survivors. Additional research to determine the pathways involved and to test the effectiveness of blood glucose control as a strategy to help protect cognition in stroke survivors and others is needed.

This research was supported in part by NIA grants AG068410, AG051827, AG024824, AG050699, AG072931, AG040282, AG023629, AG15928, AG20098, and U01-NS041588.

Reference:

Levine DA, et al. Associations between vascular risk factor levels and cognitive decline among stroke survivors. JAMA Network Open. 2023;6(5):e2313879. doi:10.1001/jamanetworkopen.2023.13879.