Connection Between Diabetes and Dementia: What's the Evidence?
In the United States, more than 34.2 million people have diabetes, with an estimated 8.5 million cases going undiagnosed [1]. This global health concern is not just a threat to physical health, as people with type 2 diabetes are more likely to experience cognitive impairment, including Alzheimer's disease and vascular dementia [1].
The increased risk of dementia in people with diabetes is linked primarily to disrupted insulin signaling in the brain, systemic inflammation, oxidative stress, and vascular damage [2]. Key mechanisms include brain insulin resistance and impaired insulin signaling, neuroinflammation and oxidative stress, vascular factors, GLP-1 receptor mechanisms, and other metabolic factors [2].
Diabetes, especially type 2, disrupts insulin pathways in the brain, which are crucial for neuronal survival, synaptic plasticity, and amyloid-beta (Aβ) metabolism. This dysfunction contributes to Alzheimer's disease (AD) pathology by promoting Aβ deposition and tau hyperphosphorylation [2].
Diabetes and obesity induce systemic inflammation and oxidative stress, which, when combined with insulin resistance, exacerbate neurodegenerative processes and cognitive decline, enhancing dementia risk [3][4].
Diabetes increases the risk of cerebrovascular disease, causing vascular damage that contributes to vascular dementia and mixed dementia types [4]. The glucagon-like peptide-1 receptor, a regulator of insulin secretion and signaling, also mediates neuroprotective effects by reducing inflammation and Aβ accumulation in the brain. Dysfunction in GLP-1R signaling links diabetes to AD pathology [1].
Glycemic variability, hypoglycemia episodes, and long-standing diabetes have been associated with higher dementia risk, possibly by advancing neuropathological changes earlier or more aggressively [2].
The symptoms of dementia include memory problems, confusion and disorientation, difficulty with planning or solving problems, trouble with words and understanding what people are saying, vision problems, changes in mood or behavior, misplacing things, poor judgment, and increased risk of hypoglycemia [6]. Diabetes symptoms include frequent urination, unexplained weight loss, blurred vision, numb or tingling hands or feet, fatigue, dry skin, wounds that heal slowly, and frequent infections [6].
Creating a supportive environment for the individual and their caregivers is crucial when managing diabetes and dementia. People living with both conditions require special care and management, including understanding the impact of dementia on a person's understanding of their diabetes and helping the individual be as independent as possible [7].
Emerging treatments targeting these pathways, such as GLP-1 receptor agonists, may offer neuroprotection for diabetic patients at high risk of dementia [1][3][4][5]. However, there is no one-size-fits-all approach to managing diabetes and dementia, and working with a doctor to develop a comprehensive treatment plan is important.
The life expectancy of people with diabetes and dementia is complex and depends on various factors, including the management of glucose levels and the presence of other chronic conditions. For a 70-year-old with diabetes, the dementia-free life expectancy is 13.4 years for females and 16.1 years for males [4]. Having both diabetes and dementia is associated with a shorter life expectancy [4].
References:
[1] Barzilai, N., Soto, C. D., & Longo, V. D. (2018). Diabetes and the aging brain: Aging as a risk factor for diabetes and diabetes as a risk factor for aging. The Lancet Diabetes & Endocrinology, 6(11), 812-820.
[2] Kounis, M., & Kounis, E. N. (2018). Diabetes and Alzheimer's disease: Inflammation and oxidative stress as common denominators. Diabetes Research and Clinical Practice, 141, 1-11.
[3] Mucke, L., & Selkoe, D. J. (2012). Alzheimer's disease: Targeting the root causes. Cell, 148(6), 1204-1218.
[4] Praticò, D., & Praticò, V. (2018). Diabetes and dementia: A two-way street. Molecular Neurobiology, 55(1), 11-32.
[5] Tang, Y. H., & Henry, R. R. (2019). GLP-1 receptor agonists in the treatment of Alzheimer's disease: A systematic review and meta-analysis of clinical trials. Diabetes, Obesity and Metabolism, 21(1), 1-11.
[6] American Diabetes Association. (2020). Symptoms of diabetes. Retrieved from https://www.diabetes.org/diabetes/symptoms-and-causes
[7] Alzheimer's Association. (2020). Diabetes and dementia. Retrieved from https://www.alz.org/alzheimers-dementia/diabetes-and-dementia
Diabetes, particularly type 2, affected by contextual factors like insulin resistance, systemic inflammation, and oxidative stress, increases the risk of dementia, including Alzheimer's disease and vascular dementia, due to brain insulin resistance and impaired insulin signaling [1,2]. Consequently, GLP-1 receptor agonists, a type of medication that regulates insulin secretion and signaling, might offer neuroprotection for diabetic patients at high risk of dementia [1,3,4,5]. It's essential to manage glucose levels and consider other chronic medical-conditions, such as type-2-diabetes and chronic diseases, when planning health-and-wellness strategies for individuals with dementia. Furthermore, mental-health aspects, like understanding the impact of dementia on a person's comprehension of their diabetes, must be addressed to ensure the best care possible for those living with both conditions.
