The Impact of Glucose on Cognition in Neurodegenerative Disease

Glucose dysregulation has been associated with poorer cognitive functioning in healthy adults with and without diabetes, as well as in individuals with neurodegenerative disease. In addition to cognitive changes, hyperglycemia has also been associated with brain atrophy, and this is especially true for those with the apolipoprotein E (ApoE) ε4 genotype. However, most of these studies rely on cognitive screening measures of dementia with vast variations in how cognition is assessed. This precludes the ability to make conclusive inferences from findings that have not assessed cognition consistently nor comprehensively.

In the present study, the effects of glucose on cognition were examined across healthy aging, and two neurodegenerative diseases, namely Alzheimer’s (AD) and Parkinson’s disease (PD), with the goal of assessing cognition in a detailed and standardized manner across cohorts. Data from the Ontario Neurodegenerative Disease Research Initiative was used to assess three cohorts of healthy adults and individuals with AD and PD. The primary interest was to analyze the effects of elevated glucose levels on cognition after controlling for related covariates of triglycerides, hypertension, and smoking. Secondary analyses examined the roles of genetics, and brain volume with glucose.

Higher glucose levels were differentially related to disease status and cognitive abilities after controlling for the effects of triglycerides, hypertension, and smoking. In healthy adults and those with PD, glucose levels were associated with poorer cognition, but not in those with AD. Among healthy adults, this effect was due to worse language and visuospatial abilities whereas widespread cognitive changes over domain-specific impairment was observed in those with PD. In AD, glucose levels were not associated with cognition. No significant interaction emerged between ApoE-ε4 carriers and glucose in neurodegenerative disease. An interaction between lower brain volume and poorer cognition was observed among those with higher glucose levels in the healthy adult group but not in the PD or AD groups.

Hyperglycemia appears to have a different relationship in those with and without neurodegenerative disease. In healthy adults, it may be possible that even glucose levels within the normal range may be exerting deleterious effects that manifest clinically, affecting both cognition and brain volume. In neurodegenerative disease, more research is needed to understand the complex relationship between hyperglycemia and specific disease pathology. With the consistent increase in both diabetes and dementia, close monitoring of glucose levels may be a potential modifiable risk factor that contributes to optimal brain health to reduce the risk of a dementia diagnosis.