Diabetes mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose levels, has been associated with an increased risk of dementia, including Alzheimer’s disease (AD) and vascular dementia (VD). This complex relationship involves several mechanisms, such as insulin resistance, hyperglycemia, neuroinflammation and energy dysregulation.
Epidemiological studies have demonstrated a strong association between type 2 diabetes (T2DM) and cognitive dysfunction, ranging from mild cognitive impairment to dementia. This relationship begins in middle age and intensifies over time, with the duration and severity of diabetes significantly influencing the risk of developing cognitive problems.
Although the connection between T2D and dementia is clear, the impact of diabetes treatment on the risk of incident dementia or the progression of pre-existing cognitive impairment remains under investigation. Several classes of antidiabetic medications have been studied, and the results point to varying effects between them.
Metformin, one of the most used medications in the treatment of DM2, has shown promising results in reducing the risk of dementia. Clinical studies indicate that the use of metformin can improve cognitive functions in diabetic patients, especially at higher doses and in younger patients with elevated insulin levels. However, more research is needed to confirm its effectiveness compared to other drug classes, such as sulfonylureas.
Dipeptidyl peptidase-4 (DPP-4) inhibitors have also shown promise in preventing dementia in patients with T2DM. These medications, in addition to helping with glycemic control, appear to have beneficial effects on cognitive functioning.
On the other hand, the use of insulin, especially in high doses and associated with episodes of severe hypoglycemia, has been associated with an increased risk of dementia. Severe hypoglycemia, a complication of insulin treatment, can lead to brain damage and contribute to cognitive decline.
New therapeutic approaches, such as the use of peroxisome proliferator-activated receptor gamma (PPARγ) agonists and glucagon-like peptide-1 (GLP-1) receptor agonists, have demonstrated potential to improve insulin sensitivity and protect insulin function. cognitive function in patients with diabetes.
In short, the relationship between diabetes and dementia is a constantly evolving field of research, with new discoveries and challenges to be overcome. Adequate glycemic control, treatment of insulin resistance, and prevention of hypoglycemia are important strategies to reduce the risk of dementia in diabetic patients. The development of new therapies that aim not only at glycemic control, but also at protecting cognitive function, represents a promising area in the search for better results for patients. (Amaral et al., 2020; Macmillan et al., 2018; Tang et al., 2022; Willmann et al., 2020).
Reference :
AMARAL, Lara Medeiros et al. Association between glycemic control in diabetic patients and reduced risk of dementia: a literature review. Brazilian Journal of Health Review, v. 3, no. 3, p. 6252-6259, 2020.
MACMILLAN, Jacqueline Mx et al. Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis. BMJ Open Diabetes Research and Care, vol. 6, no. 1, p. e000563, 2018.
TANG, Xin et al. Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes. BMJ Open Diabetes Research and Care, vol. 10, no. 5, p. e002894, 2022.
WILLMANN, Caroline et al. Insulin sensitivity predicts cognitive decline in individuals with prediabetes. BMJ Open Diabetes Research and Care, vol. 8, no. 2, p. e001741, 2020.
