The Triad of Atrial Fibrillation, Dementia, and Type 2 Diabetes: A Narrative Review of a Complex Interplay

Author(s): Syed Owais Akhtar, Syeda Shanzeh Fatima, Jupalle Mounika, Ussama Shafaqat, Yusairah Abdullah, Muhammad Aamir, Mahnoor Ahmed, Nadir Akhtar

Dementia is on the rise as a public health burden and age-related atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) constitute two known substantial risk factors for dementia. In this review, we discuss the complex relationship between these three states and propose potential mechanisms for their association based on interactions among them; in addition, possible clinical implications are addressed. AF is a frequent heart rhythm disorder that has been repeatedly associated with an increased risk of dementia. The association is probably mediated via numerous mechanisms, including a common pathway such as stroke or shared risk factors (inflammation and vascular dysfunction) in addition to the direct effects of atrial fibrillation on cerebral blood flow and oxygenation. Type 2 diabetes (T2D), a metabolic disorder related to insulin resistance, is another risk factor of dementia that has been demonstrated independently. Type 3 diabetes” is a now commonly used term and indicates the possibility of Alzheimer's disease being associated with brain insulin resistance. Several candidate mechanisms have been proposed to account for the relationship between T2D and dementia, including a direct impact of insulin resistance on brain function impaired by hyperglycemia-induced oxidative stress/inflammation or microvascular complications in cerebral blood vessels.

Conclusions: The combination of AF and T2D seems to be a risk factor potentiation for dementia, likely related to common cardiovascular risk factors, similar pathophysiological mechanisms as well as increased vulnerability toward the consequences of AF in diabetic patients. And this speaks to the importance of having an entire patient care package. The second step is to make sure that AF among patients with T2D would not go undetected and untreated, as efficient control of modifiable risk factors including blood pressure, glycemia or lipid profile involves central measures in targeted glucose-lowering therapy; early detection and management matter. Even more importantly, this high-risk population needs personalized strategies for stroke prevention. Additional studies are necessary to understand better the intricate relationship among AF, T2D, and dementia. Furthermore, large-scale prospective studies are particularly necessary to determine the temporal relationships and causal pathways. In the long term, by better understanding how this interaction occurs, we may develop new therapies that target common pathways and ultimately reduce the rapidly expanding burden of dementia in these patients.