Causal cardiovascular risk factors for dementia - insights from observational and genetic studies

The escalating prevalence of dementia worldwide necessitates preventive strategies to mitigate its extensive health, psychological, and social impacts. As the prevalence of dementia continues to rise, gaining insights into its risk factors and causes become paramount, given the absence of a definitive cure. Cardiovascular disease has emerged as a prominent player in the complex landscape of dementia. Preventing, dyslipidaemia, unhealthy Western type diets, hypertension, diabetes, being overweight, physical inactivity, smoking, and high alcohol intake have the potential to diminish not only cardiovascular disease but also dementia. The purpose of this review is to present our current understanding of cardiovascular risk factors for Alzheimer's disease (AD) and vascular dementia (VaD) by using clinical human data from observational, genetic studies and clinical trials, while elaborating on potential mechanisms. Hypertension and type 2 diabetes surface as significant causal risk factors for both AD and VaD, as consistently illustrated in observational and Mendelian randomization studies. Antihypertensive drugs and physical activity have been shown to improve cognitive function in clinical trials. Important to note is, that robust genome wide associations studies are lacking for VaD, and indeed more and prolonged clinical trials are needed to establish these findings and investigate other risk factors. Trials should strategically target individuals at the highest dementia risk, identified using risk charts incorporating genetic markers, biomarkers, and cardiovascular risk factors. Understanding causal risk factors for dementia will optimise preventive measures, and implementation of well-known therapeutics can halt or alleviate dementia symptoms if started early. Needless to mention is that future health policies should prioritise primordial prevention from early childhood to prevent risk factors from even occurring in the first place. Together, understanding the role of cardiovascular risk factors in dementia, improving GWASs for VaD, and advancing clinical trials are crucial steps in addressing this significant public health challenge.