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Link Between Insulin Resistance and Cognitive Dysfunction

Apr 29, 2017

Could diabetes cause increased rates of dementia?

With both the prevalence of diabetes and dementia increasing, many scientists have begun to question whether there could be a link between the two. The long prodromal phase of both dementia and diabetes mellitus has made establishing a relationship difficult. New research has shown that the brain, previously thought to be an insulin insensitive organ, acts on receptors that affect cognition and memory. Additionally, metabolic syndrome (MetS), known to be a precursor for diabetes, central obesity, and insulin resistance, may be a potential precursor for dementia as well.

Researchers designed an observational cohort study of postmenopausal Danish women called the Prospective Epidemiological Risk Factor (PERF) Study to examine age-related diseases. The study population was made of participants who completed valid cognitive baseline examinations and the follow-up examination. Cognitive dysfunction at baseline and missing data on confounders on any examination led to exclusion from the final analysis. To assess cognitive dysfunction, patients were given the six-item Short Blessed Test at baseline and follow up, with scores ranging from 0-28 and a score greater than or equal to 10 being indicative of impairment. The second test given was the category fluency test with animal naming (CFT), with a score less than than or equal to 14 being consistent with dementia. Metabolic syndrome was defined as being overweight and having two or more of the following conditions:  high triglycerides >1.7 mmol/L, low HDL cholesterol <1.29 mmol/L, high fasting plasma glucose >5.6 mmol/L, or previously diagnosed type 2 diabetes mellitus or hypertension. Subjects without MetS were divided into three groups based on an obese BMI, presence of 1-4 MetS risk factors with a non-obese BMI, or having no risk factors. The homeostasis model assessment risk index (HOMA-IR) was used to calculate the degree of insulin resistance (IR) by multiplying fasting plasma glucose by the concentration of insulin and dividing that number by 22.5.

A total of 1,759 women, with an average age of 68 years at baseline, were included in the final analysis and followed over a 15-year total period. The cognitive test determined that 80 women had cognitive dysfunction on both the SBT and CFT, while 136 women had cognitive dysfunction only on the SBT and 326 women had cognitive dysfunction on the CFT. Increased fasting plasma glucose was associated with 44% increased risk of developing cognitive dysfunction (OR 1.33, 95% CI 1.09-1.91), and having all five MetS risk factors was associated with a 3-times increased risk of cognitive dysfunction (OR 3.09, 95% CI 1.09-8.69) when compared to subjects with no risk factors. Having 1-4 MetS risk factors or MetS was not associated with increased risk of cognitive dysfunction at follow-up. For every unit of increase on the HOMA-I scale, the risk of cognitive dysfunction increased by 8-10% and subjects above the HOMA-IR threshold of 2.6 had a 47% increased risk of cognitive dysfunction compared to patients below the threshold (OR 1.47, 95% CI 1.09-1.99).

This study showed a strong association between fasting blood glucose and increased risk of cognitive dysfunction. There was also an increased risk of cognitive dysfunction in women who had a higher insulin resistance score, and women with a very poor metabolic profile. This test is limited in application due to exclusion of men and no statistics of the racial diversity of the study, and the influence of genetics on the development of dementia is not assessed. Further study needed in a larger and more diverse population could potentially be achieved via an observational cause-series study

Practice Pearls:

  • Risk of cognitive dysfunction increases with poor control of glucose in postmenopausal women.
  • Having a very poor metabolic profile may increase the risk of developing cognitive dysfunction.
  • Insulin resistance may be one factor in the development of diseases like dementia.


Neergaard, Jesper S., Katrine Dragsbæk, Claus Christiansen, Henning B. Nielsen, Susanne Brix, Morten A. Karsdal, and Kim Henriksen. “Metabolic Syndrome, Insulin Resistance and Cognitive Dysfunction: Does your metabolic profile affect your brain?” Diabetes (2017) Web.


Priscilla Rettman, BS, PharmD Candidate 2017, Philadelphia College of Osteopathic Medicine- GA Campus