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Cognitive Impairments from Microvascular Damage

By Jenn Cook

As of 2017, type-2 diabetes (T2D) accounted for 91.2% of individuals diagnosed with diabetes in America. It is the more common diagnosis for adults over the age of 65 with a greater body mass index (Xu et al., 2018). Type-2 diabetes differs from type-1 due to the initial inability for the pancreas to produce enough insulin, the hormone that breaks down glucose to use as energy. Due to the increased glucose concentration, the pancreas then tries to then produce more insulin and blood sugar becomes increased (Deshpande et al., 2008). A hormone typically released alongside insulin is amylin, which is responsible for regulating blood sugar, preventing fatty acid release, and invoking the feeling of fullness after eating. With increased insulin, more amylin is produced and can lead to brain damage. Its neurotoxic effects are observed within damaged cells in the temporal lobe, the cortical lobe known for memory, along with disrupted blood vessels throughout the central nervous system (Pruzin et al., 2018).

A study using rat models discovered cortical injury as a result of complications from T2D, specifically when amylin is involved (Ly et al., 2017). Three groups of rats were observed: a control group with no manipulations, one with amylin administered from human pancreatic cells (HIP), and the last group having the amylin gene removed while receiving amyling injections (AKO). All groups were tested on their behavior before undergoing magnetic resonance imaging (MRI) and tissue collection to observe any changes in blood vessels throughout their brains. The behavioral tests consisted of an inclined plane to observe muscle tone. When they would begin free-falling at increasing angles, a cylinder test was administered to observe any abnormalities in their forepaws when touching a vertical wall. Lastly, a Morris water maze (MWM) was used to assess memory and locomotor activity as rats swam to locate a platform. Afterwards, MRI data was collected to identify any structural abnormalities in the brain alongside tissue collection to identify blood flow.

The results from this study exhibited vast differences between the groups through severity in cognitive impairment which presented similarities to dementia. Ly and colleagues (2017) discovered cognitive dysfunction in the rats with increased amylin expression. Whereas the purpose of the AKO rats was to depict any similar proteins that lead to the onset of dementia, HIP rats allowed the researchers to draw conclusions about vascular damage and cognitive impairment. Despite the WT rats showing no behavioral changes and performed as expected, HIP rats exhibited impairments in balance and locomotor activity. When in the MWM, the HIP and WT rats swam at similar speeds, though it took longer for the HIP rats to discover the platform. When tested 24 hours later, there were no differences in the time it took to remember the location, suggesting that amylin affects short-term memory and not long-term. This is supported by identifying volume expansion of cerebrospinal fluid and a reduction in hippocampal size, the structure within the temporal lobe responsible for learning and memory. Examining the tissues showed myelin reduction, along with a rise in microhemorrhages and disrupted blood vessels among the HIP rats. This indicates that vascular amylin deposition indirectly destroys the connection between two neurons, as signals cannot be sent through the cells without fast communication.

Along with other severe medical complications as a result of microvascular injury, adults living with untreated T2D for a period of time are shown to have a gradual decline in cognitive function. This is particularly due to complications from microvascular injury located in the brain, which can cause reduced cortical volume and obstructed blood vessels in tissue (Biessels & Despa, 2018). These damages present as impairments in processing speed, executive function, attention, and visual and verbal memory. Though T2D does not progress into Alzheimer’s disease, there is an elevated risk for the development of vascular dementia as one ages (van Duinkerken & Ryan, 2020). A large array of options are available to decelerate the progression of cognitive impairment through indirectly preventing further atrophy, that can include lifestyle changes or prescription medicine.

By adopting a healthy lifestyle through exercise and a diet low in fats, the rate of cortical damage slows and decline is not as severe. Incorporating omega fatty acids, antioxidants, and vitamins into one’s diet act as neuroprotective factors for further damage and can even prevent toxicity in individuals at risk for T2D (Sharma et al., 2020). A multitude of pharmacological agents are available, as well, to reduce blood sugar levels and inhibit further injury. Typically, these drugs stimulate pancreatic cells to release insulin and break down glucose. If these possibilities do not work, people are able to receive manual insulin injections and control blood sugar (Wu et al., 2014). It is best to keep in mind treatment strategies for every person is individualized and what may work for one person may not be beneficial for another. Since each body reacts differently to certain medications or even dietary plans, one should find treatment options that fit best for them.


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Ly, H., Verma, N., Wu, F., Liu, M., Saatman, K.E., Nelson, P.T., … Despa, F. (2017). Brain Microvascular Injury and White Matter Disease Provoked by Diabetes-Associated Hyperamylinemia. Annals of Neurology, 82(2), 208-222. Doi: 10.1002/ana.24992

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Sharma, G., Parihar, A., Talaiya, T., Dubey, K., Porwal, B., & Parihar, M.S. (2020). Cognitive impairments in type 2 diabetes, risk factors and preventive strategies. Journal of Basic and Clinical Physiology and Pharmacology, 1-14. Doi: 10.1515/jbcpp-2019-0105

Van Duinkerken, E. & Ryan, C.M. (2020). Diabetes mellitus in the young and old: Effects on cognitive functioning across the life span. Neurobiology of Disease, 134, 1-10. Doi: 10.1016/j.nbd.2019.104608

Wu, Y., Ding, Y., Tanaka, Y., & Zhang, W. (2014). Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention. International Journal of Medical Sciences, 11(11), 1185-1200. Doi: 10.7150/ijms.10001

Xu, G., Liu, B., Sun, Y., Du, Y., Snetselaar, L.G., Hu, F.B., & Bao, W. (2018). Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. British Medical Journal, 362, 1-7. Doi: 10.1136/bmj.k1497

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1 Comment

Holly A
Holly A
Aug 01, 2022

Great bblog I enjoyed reading

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