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Diabetes, cognitive impairment, dementia- the role of Liraglutide

SUMMARY

There are approximately 50 million people worldwide with dementia; of these, it is estimated that more than 7 million have diabetes. The number of people developing dementia is projected to reach 152 million by 2050, with a current estimated worldwide cost of US$818 billion, making better pharmacological therapies for patients with dementia an urgent priority. Given the large number of people worldwide with type 2 diabetes, and the substantially increased risk of dementia incidence among these individuals, a pharmacological treat- ment that reduces the incidence of dementia in people with type 2 diabetes would have a large impact.

In addition to its glucose- lowering effect, GLP-1 RAs (Glucagon Like Peptide-1 receptor agonists) may have specific properties for preventing dementia.

Liraglutide is a GLP-1RA.

In humans, it was recently demonstrated that liraglutide slowed down the decline in memory function independently of weight loss in a group of patients with obesity and prediabetes or early type 2 diabetes.

REVIEW

Diabetes mellitus has transformed in recent years from an illness primarily associated with metabolic Disorders to a complicated disease with potential implications that extend well beyond glycemic Control. A growing number of studies are starting to demonstrate how diabetes may affect Cognitive function as its prevalence rises worldwide.

Diabetes, that is defined by the body’s inability of effectively managing blood glucose levels, is well-known for the harm that it may lead to, including retinopathy, neuropathy, and cardiovascular disease. However, the potential effect on cognitive abilities has received a lesser amount of focus.

Deficits in memory, attention, language, and executive function referred to as cognitive impairment Provide an enormous challenge to those who are affected by it, their families, and medical Professionals.

Diabetes-related cognitive impairment is greatly impacted by oxidative stress and inflammation. Hyperglycemia increases the production of reactive oxygen species (ROS) and reactive nitrogen species, which produce oxidative damage in an array of cellular pathways. Oxidative stress is linked to neuronal damage via the accumulation of excitatory amino acids, such as glutamate and osmotic shocks. In addition, AGEs provoke brain immune cells called microglia, that can harm neurons. Diabetes exacerbates inflammation and increases the release of inflammatory cytokines, which exacerbate cognitive deterioration in those who have the disease.

What research has shown about the relationship between diabetes and cognitive decline:

Compared to those without diabetes, those with Type I diabetes have a higher risk of dementia. A study found that people with Type I diabetes had a 93% increased risk of dementia. According to a 2021 study conducted for Kaiser Permanente Northern California, older persons with Type I diabetes who were hospitalized for both highs and lows in blood sugar were six times more likely to acquire dementia than those who were only hospitalized for one blood sugar extreme.

Elevated blood sugar levels and Alzheimer’s disease are strongly correlated. According to one study, beta-amyloid protein, one of the key brain proteins associated with Alzheimer’s disease, dramatically increased in those with high blood sugar, including those with Type 2 diabetes.

Early-stage Type 2 diabetics have symptoms of brain impairment. Indeed, the brains of study participants exhibited elevated levels of insulin resistance and a diminished capacity to utilize glucose for supporting regular brain activity.

People who have Type 2 diabetes have rapid cognitive impairment, particularly in the areas of executive function and speed of information processing. According to a different study, those with Type 2 diabetes who developed the disease earlier in life are more likely to develop dementia. Hemoglobin A1C (HbAIC) levels in the blood were linked to the early effects of diabetes on the brain. Researchers discovered that memory impairments commonly linked to the hippocampal region of the brain were present in individuals with diabetes even if they had the disease for less than ten years.

Researchers discovered that the hippocampi were smaller in diabetics than in non-diabetics. Additionally, they found a correlation between the drops in hippocampus size and blood levels of HbA1C. This finding raises the possibility that HbAIC could be a marker of hippocampal function and/or the beginning of memory loss.

Alzheimer’s disease is known to be associated with the amyloid precursor protein gene, often known as APP or the “parent molecule of beta-amyloid.” The insulin pathway is impacted by this gene as well.

Diabetes is characterized by disruption of the insulin system, and studies on the APP gene may provide a treatment target for both conditions.

Diabetes and dementia are two age-related conditions that are extremely common and pose significant health and socioeconomic problems throughout the world. Compared to those without diabetes, patients with diabetes have a 1.6-fold higher risk of dementia, including vascular dementia and Alzheimer’s disease (AD), as well as an accelerated rate of cognitive decline. For people with diabetes, screening for moderate cognitive impairment should be done annually starting at age 65. Unfortunately, the available therapeutic choices are currently limited. Over the past 20 years, no new medicines have been approved globally, and the only recently approved drug in the United States has small advantages.

Globally, the projected number of individuals suffering with dementia is 50 million, with over 7 million expected to have diabetes. Improved pharmaceutical therapy for dementia patients are a top concern since the number of individuals with dementia is expected to reach 152 million by 2050 and the current estimate of the global cost of dementia is US$818 billion. A pharmaceutical treatment that lowers the incidence of dementia in people with type 2 diabetes would have a significant effect, given the number of people with type 2 diabetes worldwide and their significantly elevated risk of dementia incidence.

In addition to its glucose- lowering effect, GLP-1 RAs may have specific properties for preventing dementia.

Recently, liraglutide was shown to slow down the deterioration of memory function in humans, even in the absence of weight loss, when administered to a group of obese patients with prediabetes or early-stage type 2 diabetes.

Disclaimer: The contents of this article are for medical information purposes only and does not constitute a medical advice in any form. This also does not constitute a doctor patient relationship.

Acknowledgement: The content of this page is acknowledged as the knowledge of references mentioned below. All due credit is given to the authors of the source references.

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