Podcast

Ruth Frikke-Schmidt, MD, DMS, on How High Body Mass Index Increases Risk of Vascular-Related Dementia in European Cohorts

Key Highlights

  • Mendelian randomization data from Danish and UK cohorts suggest high BMI is a causal risk factor for vascular dementia, reinforcing obesity as a modifiable target.

  • Hypertension mediates much of the BMI–dementia association, underscoring weight management and blood pressure control as key prevention strategies.

  • The overall findings emphasize the importance of early cardiometabolic intervention, supporting the principle that what benefits heart health also protects brain health.

In this podcast, Ruth Frikke-Schmidt, MD, DMSc, discusses whether elevated BMI is a causal risk factor for vascular-related dementia and assesses the extent to which blood pressure and other metabolic factors mediate this association, offering clinically relevant insights for dementia prevention strategies.

Additional Resources

Nordestgaard LT, Luo J, Emanuelsson F, et al. High body mass index as a causal risk factor for vascular-related dementia: a mendelian randomization study. J Clin Endocrinol Metab. Published online January 22, 2026. doi:10.1210/clinem/dgaf662

Transcript

Consultant360: Hello, everyone, and welcome to another installment of Podcast360, your go-to resource for medical news and clinical updates. I'm your moderator, Ashton Stahl, with Consultant360, a multidisciplinary medical information network.

High BMI has long been associated with cardiometabolic disease, but its causal role in dementia has remained uncertain. New evidence, published in the Journal of Clinical Endocrinology and Metabolism, reports that elevated BMI is likely a causal risk factor for vascular-related dementia. Findings are based on large population cohorts from Denmark and the United Kingdom and apply genetic methods to strengthen causal inference. Here to speak about that study with us today is Dr. Ruth Frikke-Schmidt. She is chief physician at the Copenhagen University Hospital - Rigshospitalet and clinical professor at the  University of Copenhagen.

Alright, from your perspective, why is this study important in clarifying the long-debated relationship between obesity and dementia risk?

Ruth Frikke-Schmidt, MD, DMSc: It is very important because obesity or overweight and related risk factors are actionable targets for us to combat and consequently prevent a large fraction of dementia that is evident in our societies, where the populations are aging. And what do I mean with actionable? I mean that we have prevention and treatments against obesity and overweight, so we can really do something about it. And what we do with this study is that we create the evidence that there is a direct causal association between overweight and future risk of especially vascular-related dementia. There have been many studies out there showing an association but not with the layer of causality underneath. We need to see that risk factors are indeed the direct cause in order to ensure that the prevention or treatment is efficient.

Consultant360: So you all found that high BMI is likely a causal risk factor for vascular-related dementia. So how does this shift the way clinicians should think about obesity in midlife versus later life?

Frikke-Schmidt: What we can say is something about obesity or overweight in general. I'm talking about at the general population level, that when we see overweight, then it's associated causally with an increased risk of vascular-related dementia. It's another situation when you have overt dementia, then you, of course, have to talk with your doctor what the right treatment and follow-up should be. With this study we are talking about the potential for early prevention in midlife, . So our finding is really an argument for preventing early because we can see that earlier overweight is associated closely with later risk of dementia, not only diabetes. Overweight is also associated with high blood pressure, another risk factor for dementia easy to treat and prevent. So it's really important that we now can say that obesity in itself, is a modifiable risk factor that is causal, and, thereby, we can do something about the risk in later life for dementia.

Consultant360: So blood pressure mediated a significant portion of the BMI and dementia association. So in real-world practice, what opportunities does this create for earlier or more targeted intervention?

Frikke-Schmidt: It's an important question, and I see our story as a very positive one because we directly point at 2 highly modifiable risk factors, obesity and high blood pressure, that can be treated or prevented and subsequently lower your future risk of dementia. We have really good medicines, drugs well established, safe for preventing or for treating high blood pressure. So  by targeting obesity with  lifestyle changes, or weight-losing medicines, we can lose weight but also lower the blood pressure, because obesity partly is a cause of high blood pressure. And if the blood pressure needs to be further lowered,  we have all the safe hypertension medicines that are efficient..

Consultant360: So this research differentiates vascular-related dementia from Alzheimer's disease. So why is that distinction clinically meaningful, and how might it influence future prevention strategies?

Frikke-Schmidt: We have the frame called dementia in general, and there are some common subtypes of that. We have Alzheimer's disease, which is diagnosed in 60 to 70% of people with dementia, and that's characterized with degenerative pathologies. So that's kind of sticky protein plaques in the brain causing harm to the brain tissue resulting in for example memory problems. Then we have the more vascular-oriented dementia that originates from atherosclerosis, narrowing of the blood vessels to the brain. They can clot, and we can get a stroke, or small strokes, and then blood flow is diminished to the brain. Consequently, brain tissue damage occurs, and a high risk of vascular-related dementia because it kind of comes from narrowing of the brain vessels. But there is also significant overlap between Alzheimer's disease and vascular dementia. So we can say that even though our findings are kind of more clear for the vascular forms of dementia, it is kind of safe to say that what is good for the heart is good for the brain because we also know now that narrowing of cerebral brain vessels can also  trigger neurodegenerative processes leading to the Alzheimer's disease subtype. But our specific study is  especially strong for risk of  vascular dementia, which is a large fraction of dementia also. We have actually upcoming data showing that also other cardiovascular modifiable risk factors as  cholesterol,  type 2 diabetes,  and smoking are indeed direct causal factors for  dementia in general - again more clearly for vascular dementia, but also for Alzheimer's disease. So again, it is safe for us to say now that what is in general good for the heart is good for the brain. This opens up for a huge preventive potential for  preserving brain health.

Consultant360: Looking ahead, how could findings like these inform multidisciplinary prevention approaches that combine cardiometabolic management with cognitive health?

Frikke-Schmidt: Yes, that's so important, and it's kind of something we address and work heavily on in preventive medicine for cardiovascular health and brain health. And it is multifaceted. As you say, there are  state of the art lifestyle intervention trials,  where  a combined lifestyle change is tested in randomized clinical trials and improves cognition. So there is much to gain for ambitious preventive strategies, also because it has been very  difficult to develop efficient, curative or relieving medicines for dementia. So while we wait for that, it's so important that we all go together and are ambitious about prevention strategies at the societal level. We should advocate for brain health like we advocate for cardiovascular health.

Consultant360: Thank you for speaking with us today, Dr. Frikke-Schmidt. For more cardiometabolic and dementia content, visit consultant360.com.

This transcript was edited for clarity.

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