High glucose levels associated with increased risk of dementia

Image: PD 

1. In patients without diabetes there was a monotonically increasing association between glucose level and risk of dementia; the same association between higher glucose level and risk of dementia was seen in patients with diabetes in the higher range of glucose levels. 

2. The study controlled for variables such as age, gender, educational level, level of exercise, and coincident diseases such as stroke and heart disease, but the prospective cohort study design could not exclude the potential for unmeasured confounding variables. 

Evidence Rating Level: 2 (Good)

Study Rundown: This prospective, community-based cohort study showed that in patients with and without diabetes, increasing levels of blood glucose are associated with an increased risk of developing dementia. The results provide high-quality epidemiological evidence suggesting a link between glucose metabolism and the incidence of dementia.   Strengths of the study include the large, prospective sample size with minimal attrition and efforts to control for a number of reasonable confounding factors.

Limitations include the inability to control for unmeasured confounding variables, which is inherent in the prospective cohort study design; the self-reported nature of many co-variates; limited generalizability given a largely white cohort; and definitional issues, such as how dementia was not broken into pathological subtypes and how diabetes status was determined in the database on the basis of whether an individual had filled prescriptions for diabetes-related drugs.  Furthermore, the direction of causality could not be definitively determined in this study.  It is possible that the development of dementia in patients with diabetes led to a decline in self-care, but this direction of association is less likely given the similar association seen in patients without diabetes, who also experienced an increased risk of incident dementia in association with higher glucose levels.  Overall, these findings provide grounding for future studies investigating the specific mechanisms underlying the association between higher blood glucose levels and risk of dementia in patients with and without diabetes.

Click to read the study, published today in NEJM

Relevant Reading: Diabetes and other risk factors for dementia

In-Depth [prospective cohort study]: This study included 839 men and 1228 women without dementia and a median baseline age of 76 years who were followed for a median of 6.8 years. There were 232 patients with diabetes, defined as having two diabetes-related prescriptions filled per year. Average glucose levels for each subject were represented in an aggregate measure including both fasting and random glucose levels (35,246 samples) and glycolated hemoglobin levels (10,208 samples); participants were assessed for incident dementia through cognitive screening every 2 years.

Among participants without diabetes, the risk of dementia increased with increasing glucose levels over the preceding five-year period (P=0.01). For an average glucose level of 115 mg/dl, as compared with 100 mg/dl, the adjusted hazard ratio for dementia was 1.18 (95% confidence interval, 1.04 to 1.33); this association strengthened with higher levels of average blood glucose, suggesting a monotonic relationship.  Among participants with diabetes, those with the highest levels of glucose had an increased risk of incident dementia (P=0.002).

By Matthew Growdon and Mitalee Patil

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