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Does Diabetes Impact Long-Term Cognition?

Feb 17, 2018

Study in England links high HbA1c levels to long-term cognitive decline.

Previously, the link between dementia and diabetes was labeled as controversial.  However, the relationship between the two is now well-established owing to numerous studies that explored the connection. A systematic review completed by GJ Biessels et al., uncovered the incidence of any type of dementia, including Alzheimer’s disease and vascular dementia, to be higher in patients who had diabetes. Another study conducted by Paul Crane and colleagues showed higher glucose levels to be a risk factor for development of dementia, even for those individuals who did not have diabetes. But, are diabetes, high A1c levels, and cognitive decline also intertwined? In hopes of uncovering whether the long-term cognitive decline is linked to diabetes, researchers in England studied population from the English Longitudinal Study of Ageing (ELSA).


ELSA was a prospective cohort conducted on a national level that was representative of men and women living in England who were above 50 years of age. Subjects from the ELSA study who had complete clinical assessments including the HbA1c levels and cognitive evaluations were enrolled into this study. To assess the cognition, subjects were given a memory reassessment that consisted of an immediate and delayed recall of 10 unrelated words. A composite score was calculated by adding the scores of two individual memory tests. By naming names of animals during a period of 60 seconds, each individual’s executive function was evaluated. Lastly, participants were asked questions regarding orientation; subjects were asked four date-related questions, such as naming the day of the week, day of the month, or year. Better performance was correlated to higher scores in any of the tests performed. A composite z score was estimated for each participant in the study by averaging the scores of the above three tests.

The study enrolled 5,198 participants with average age of 65.6 +/- 9.4 years; enrolled subjects included 22.9% who had pre-diabetes and 8.6% of individuals with diabetes.  Cross-sectional analysis determined that baseline A1c levels were directly linked to cognitive and executive function, as well as the memory performance regardless of age or sex of the individual. For instance, individuals with diabetes had an average memory score of 9.4 +/- 3.3, compared to 10.5 +/- 3.4 score that was seen in patients without diabetes, p-value <0.001. However, orientation scores were not found to be related to HbA1c levels. Analysis of the 10-year long longitudinal effect of HbA1c to change in cognitive function showed that each increase in HbA1c by 1 mmol/mol led to further decline in cognitive function. Regardless of age or sex, the relationship was statistically significant for decline in cognition, memory and executive function, p-values 0.002, 0.019 and <0.001, respectively. Once again, orientation test was not related to increased HbA1c,, p-value 0.167. Over time, cognition, memory scores, and executive functions decreased more rapidly in patients with HbA1c levels greater than 7%.

Fanfan Zheng and colleagues observed a trend in cognitive decline over the period of 10 years in subjects with diabetes. Moreover, increased HbA1c  levels lead to a faster cognitive decline regardless of diabetes diagnosis. Memory and executive function were mostly affected during the period of 10 years; researchers argue that this decline could be related to high circulating glucose levels. By inducing amyloid accumulation, increasing microvascular disease in CNS, and by leading to depression, obesity and hyperlipidemia, diabetes can potentiate cognitive decline. Yet, true mechanisms by which diabetes affects cognitive decline are unknown. Early recognition of diabetes risk factors and proactive management of DM are important to prevent possible decline in cognition. But, can the cognitive decline be slowed by having optimized HbA1c levels? To answer this question, future studies need to be completed that focus on benefits of normalized HbA1c ranges and cognition.

Practice Pearls:

  • Higher baseline HbA1c  levels correlates with lower cognition, memory, and executive function regardless of age or gender of an individual.
  • Cognition, memory, and executive function decline more rapidly in patients with diabetes than they do in non-diabetic patients.
  • Orientation to day, month, and year is not affected by HbA1c


Fanfan Zheng, et al. “HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.” Diabetologia. 2017. https://link.springer.com/article/10.1007/s00125-017-4541-7.  Accessed Jan 2018.

GJ Biessels, et al. “Risk of dementia in diabetes mellitus: a systematic review.” Lancet Neurology. 2006. http://www.thelancet.com/retrieve/pii/S1474442205702842. Accessed Jan 2018.

Paul Crane, et al. “Glucose Levels and Risk of Dementia.” New England Journal of Medicine. 2013. http://www.nejm.org/doi/full/10.1056/NEJMoa1215740.  Accessed on Jan 2018.

Lamija Zimic, PharmD(c), University of South Florida, College of Pharmacy