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Normalizing Glucose Prevents Cognitive Decline

Jul 28, 2020
Editor: Steve Freed, R.PH., CDE

Author: Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy

Type 2 diabetes damages brain regions that govern memory, movement, and visual processing; normalizing glucose levels can help.

Older adults can often experience cognitive decline—more progressively, they can develop dementia or even Alzheimer’s disease. There are a variety of causes that can lead to cognitive decline as well, with obesity and diabetes having been shown to be among the highest risks associated. An endocrinologist at CentraState Medical Center reports that “studies show that in addition to [the] loss of nerve cells, there is also a change in the way brain cells work when someone has diabetes.” Brain regions relating to memory, movement, and visual processing are all altered in patients with type 2 diabetes. This study examines the underlying connection between obesity, diabetes, and cognitive decline in older adults.

Indicators of diabetes, insulin resistance, and blood pressure were evaluated with the rate of cognitive decline in this prospective population-based study. The association of these factors with cognitive decline was observed in patients with and without obesity. To assess cognitive function at baseline, participants were given neuropsychological tests that looked at processing speed, behavioral control function, memory, language, and ability to identify a stimulus and its location. Composite scores were calculated after the study from the tests’ average, and a slope was created that defined each participant’s cognitive decline over time. Using the modified Center for Epidemiologic Studies Depression scale (mCESD), data on body mass index (BMI), waist-hip ratio (WHR), blood pressure, and depressive symptoms were collected. To determine obesity’s overall influence on cognitive decline, researchers used only the WHR instead of BMI since it was capable of measuring central or abdominal obesity.

Additionally, researchers collected fasting blood glucose samples to observe glucose, insulin resistance, HbA1c, adiponectin, and APOE genotyping, which assess susceptibility for Alzheimer’s Disease. HbA1c levels had shown to be the strongest metabolic predictor, which prompted researchers to solely use HbA1c to represent glycemia for all of the other multivariable analyses. Linear regression models further examined the connections between all of the individual components identified and cognitive deterioration.

Adjusted analysis of cognitive outcome revealed that out of all the individual predictors, only the association of higher HbA1c levels was seen with a decline in cognitive function. After examining possible connections with the components inspected from the fasting blood glucose, Age (coefficient= -0.26; SE= 0.04; P < 0.001) and APOE*4 carriage (coefficient= -0.25; SE= 0.1; P = 0.023) also demonstrated strong significance with declining cognitive outcome. Within the lower WHR group, age (coefficient= -0.32; SE= 0.07; P < 0.001) and APOE*4 carriage (coefficient= -0.49; SE= 0.16; P= 0.002) were the most significant covariates. In contrast to the higher WHR group, higher HbA1c and blood glucose levels were seen to have links to faster decline in cognition in both unadjusted (coefficient= -0.11; SE= 0.05; P= 0.32) and adjusted models (coefficient= -0.15; SE= 0.05; P= 0.006). Furthermore, in a separate analysis, the participants who were 88 years and older only had age as the leading explanation—for participants who were aged younger than 88 years old, HbA1c levels of 6.2%, or higher predicted quicker cognitive decline. 

This study proved that the mechanism of chronic hyperglycemia was one of the most fundamental pathophysiologic links to cognitive decline. HbA1c levels were the only variable within participants with abdominal obesity that was significantly associated with cognitive decay as well. A limitation of the study was not having neuroimaging data available. From this, researchers were unable to determine how much the decline in cognitive function was due to neurodegenerative damage. Also, since inflammation, oxidative stress, and mitochondrial dysfunction occur in both diabetes and cognitive decline, further studies could see if these factors are linked between diabetes and neurodegeneration. 

Practice Pearls:

  • Hyperglycemia is evident as being a pathophysiologic link between type 2 diabetes and a decline in cognitive function.
  • Individuals younger than 88 years old with central obesity are shown to have a higher association with cognitive decline.
  • Out of all the individual predictors, only the association of higher HbA1c levels was seen with a decline in cognitive ability.


References for “Normalizing Glucose Prevents Cognitive Decline”:
Ganguli, Mary, et al. “Aging, Diabetes, Obesity, and Cognitive Decline: A Population‐Based Study.” The Journal of the American Geriatrics Society, 2020, doi: https://doi.org/10.1111/jgs.16321.

Caceres, Vanessa. “Why Cognitive Impairment Is More Common When You Have Diabetes.” US News & World Report, US News & World Report, Jul 13, 2017, health.usnews.com/health-care/patient-advice/articles/2017-07-13/why-cognitive-impairment-is-more-common-when-you-have-diabetes


Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy



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