- Vascular dementia is the second most common type of dementia, and its prevention forms a critical area of research.
- A recent study using Mendelian randomization suggests that obesity may be a causal factor for vascular-related dementia and that high blood pressure may be an involved mediator.
- The results suggest that addressing obesity and high blood pressure could help prevent vascular-related dementia.
Dementia continues to remain a common chronic condition, so experts want to continue to study possible intervention strategies that people can practically apply.
According to Alzheimers.gov, vascular dementia, which is one specific form of this condition, “is caused by conditions such as stroke that disrupt blood flow to the brain and lead to problems with memory, thinking, and behavior.”
While Alzheimer’s disease remains the most common dementia type, vascular dementia is the second most common.
A recent study published in The Journal of Clinical Endocrinology & Metabolism wanted to see if obesity was possibly a causal factor for vascular-related dementia.
The results indicated this was the case, and that the relationship was mediated in part by high blood pressure.
To examine the relationship between obesity and vascular-related dementia, researchers considered several levels of data. They used three studies to examine individual-level data, and six studies to look at summary-level data.
They looked at possible mediation factors like blood pressure and glucose (blood sugar), and also examined if these played a causal role as well in vascular-related dementia.
Researchers used Mendelian randomization, which considers certain genetic variants to see if a risk factor could have a causal relationship with an outcome. They used data from databanks like the UK Biobank in their research.
When looking at individual-level data, researchers considered body mass index (BMI) and also had other data, such as blood pressure measurements.
They took into consideration well-established genetic variants, which show a strong link to the trait in question, such as BMI. They also looked at “an extended number of genetic variants.”
In addition to examining vascular-related dementia, researchers also considered Alzheimer’s disease as an endpoint and used ischemic heart disease as a positive control.
The researchers observed that having a higher BMI was associated with a higher risk of vascular-related dementia.
When looking at the intermediate risk factors using the well-established variants, researchers found that blood pressure accounted for part of the association between BMI and vascular-related dementia.
Systolic blood pressure was responsible for about one-fifth of the association (18%), while diastolic blood pressure was responsible for one-fourth of the association.
The authors suggest that the mechanism underlying their findings on BMI and vascular dementia mediated by blood pressure is “most likely caused by the effect of high blood pressure on the brain, where higher BMI is a direct cause of higher blood pressure.”
Study author Ruth Frikke-Schmidt, MD, PhD, DMSci, Chief Physician at Copenhagen University Hospital – Rigshospitalet and Clinical Professor at University of Copenhagen, in Denmark explained the main results of the research to Medical News Today.
“Our findings show that overweight and high blood pressure are direct causes of increased dementia risk – that makes them highly actionable targets for dementia prevention at the population level,” said Frikke-Schmidt.
Dung Trinh, MD, an internist physician at MemorialCare Medical Group in Irvine, CA, and Chief Medical Officer of Healthy Brain Clinic, who was not involved in the study, also noted that:
“By using Mendelian randomization, the researchers were able to reduce many of the biases that have complicated earlier studies, such as reverse causation and confounding from lifestyle or illness. What is interesting is the consistency of the findings across multiple large population datasets and analytic approaches. The results strongly support the idea that obesity is not just correlated with vascular dementia but plays a direct role in increasing risk through vascular mechanisms.”
This research only included European individuals, so additional data is needed, and this feature limits generalizability.
The authors admit that they do not know “which set of genetic instruments is more valid,” since the well-established genetic variants and the extended set both have benefits.
They also note the heterogeneity regarding dementia diagnoses, the possibility of mixed dementia cases or other pathologies happening at the same time, and the challenge of not having data on vascular dementia subtypes.
The observational data runs the risk of reverse causation as well as other limitations, such as other involved mediators. As endpoints, researchers included vascular-related dementia and unspecified dementia in the same category.
Mendelian randomization is a very useful research method, but it also relies on certain assumptions, which are explained in this study, such as the assumption that genetic variants affect the end result “only through their effect on the risk factor of interest.”
However, the researchers conducted sensitivity analyses to test certain assumptions of Mendelian randomization. There were some indicators that the underlying assumption about variants’ effects on outcomes had some flaws for the extended number of variants.
Finally, the team focused on BMI, which can give a general reflection of weight but is not a perfect measurement. For example, it does not differentiate between lean and fat mass.
The authors note that it is hard to conclude if both lean body mass and fat increase someone’s chances of vascular-related dementia. Finally, researchers suggest a possible overestimation when adding all the mediators together.
The study results suggest that tackling obesity and high blood pressure could be helpful prevention strategies for vascular-related dementia.
Trinh noted that:
“This research reinforces that vascular health is brain health. It suggests that managing body weight—especially in midlife — along with aggressive control of blood pressure could meaningfully reduce the risk of vascular-related dementia later in life.The study shows that blood pressure mediates a substantial portion of the risk, highlighting hypertension as a key intervention point. This means that weight management and blood pressure control are not only important for cardiovascular disease, but may also represent practical, modifiable strategies for dementia prevention.”
Richard Terry, DO, MBA, an osteopathic physician specializing in family medicine and vice president of health science at Lake Erie College of Osteopathic Medicine, likewise not involved in this study, explained for MNT that “this [research] clearly demonstrates that obesity in and of itself is a risk for dementia.“
“It’s further exacerbated in patients that have high blood pressure as well, which is often a comorbidity in obese patients. Along with numerous other studies, this demonstrates that lifestyle management and weight management plays a significant role in health and can affect a person’s lifespan and produce a reduction of dementia,” concluded Terry.
