Obesity May Be a Key Driver of Vascular Dementia Risk, New Genetic Study Finds

Obesity may play a direct and causal role in the development of vascular dementia, according to a new study that highlights high blood pressure as a major pathway linking excess weight to brain damage. The findings suggest that addressing obesity and controlling blood pressure could become important, practical strategies for preventing this common form of dementia.

Dementia remains one of the most prevalent chronic neurological conditions worldwide, and its burden is expected to rise sharply as populations age. While Alzheimer’s disease is the most common type of dementia, vascular dementia ranks second and is caused by impaired blood flow to the brain, often as a result of stroke or long-term damage to blood vessels.

According to Alzheimers.gov, vascular dementia occurs when conditions such as stroke or chronic vascular injury disrupt blood supply to the brain, leading to progressive problems with memory, thinking, and behavior. Because vascular dementia is closely tied to cardiovascular health, researchers have increasingly focused on identifying modifiable risk factors that could help prevent or delay its onset.

A new study published in The Journal of Clinical Endocrinology & Metabolism adds strong genetic evidence that obesity itself is not merely associated with vascular dementia, but may actually be a causal factor. Importantly, the researchers found that elevated blood pressure explains a significant portion of this increased risk.

Using genetics to clarify cause and effect

To investigate whether obesity directly increases the risk of vascular-related dementia, researchers used a method known as Mendelian randomization. This approach leverages naturally occurring genetic variants that are strongly associated with certain traits—such as body mass index (BMI)—to determine whether those traits have a causal effect on disease outcomes.

Because genetic variants are randomly assigned at birth, Mendelian randomization can reduce many of the biases that affect traditional observational studies, including confounding factors and reverse causation. This makes it a powerful tool for exploring whether risk factors like obesity actually cause disease rather than simply being correlated with it.

The research team analyzed both individual-level data and summary-level data from multiple large population studies. Three datasets provided individual-level information, including BMI and blood pressure measurements, while six additional studies contributed summary-level genetic data. Much of the data came from large biobanks, including the UK Biobank.

In addition to vascular-related dementia, the researchers also examined Alzheimer’s disease as an outcome and included ischemic heart disease as a positive control to validate their analytical approach.

Higher BMI linked to higher dementia risk

Across the analyses, the researchers found a consistent pattern: higher BMI was associated with a greater risk of vascular-related dementia. This association held true when using well-established genetic variants linked to BMI, as well as when using an expanded set of genetic variants.

By contrast, the relationship between BMI and Alzheimer’s disease was weaker, reinforcing the idea that obesity’s impact on dementia risk may be particularly driven by vascular mechanisms rather than neurodegenerative processes alone.

Blood pressure emerges as a key mediator

To better understand how obesity increases the risk of vascular dementia, the researchers examined potential intermediate factors, including blood pressure and blood glucose levels.

Their analysis showed that blood pressure plays a significant mediating role in the relationship between BMI and vascular-related dementia. Specifically, systolic blood pressure accounted for approximately 18% of the association, while diastolic blood pressure explained about 25%.

The authors suggest that the most likely mechanism is the direct effect of obesity on blood pressure, which in turn damages the brain’s blood vessels. Elevated blood pressure is known to cause structural and functional changes in cerebral vasculature, ultimately impairing blood flow and increasing the risk of cognitive decline.

“Our findings show that overweight and high blood pressure are direct causes of increased dementia risk,” said study author Ruth Frikke-Schmidt, MD, PhD, DMSci, Chief Physician at Copenhagen University Hospital – Rigshospitalet and Clinical Professor at the University of Copenhagen. “That makes them highly actionable targets for dementia prevention at the population level.”

Experts say findings strengthen prevention message

Independent experts not involved in the study say the findings provide compelling evidence that obesity should be taken seriously as a modifiable risk factor for dementia.

Dung Trinh, MD, an internist at MemorialCare Medical Group in Irvine, California, and Chief Medical Officer of Healthy Brain Clinic, noted that Mendelian randomization helped overcome many limitations of earlier research.

“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,” Trinh said. “What is interesting is the consistency of the findings across multiple large population datasets and analytic approaches.”

He added that the results strongly support the idea that obesity does not merely coexist with vascular dementia but actively contributes to its development through vascular pathways.

Important limitations remain

Despite the strength of the genetic approach, the authors acknowledge several limitations. The study population consisted exclusively of individuals of European ancestry, which limits how broadly the findings can be applied to other ethnic groups.

There was also heterogeneity in how dementia diagnoses were defined across studies, raising the possibility that some participants may have had mixed dementia or overlapping pathologies. Additionally, the researchers lacked detailed data on specific subtypes of vascular dementia.

The study also relied on BMI as a measure of obesity, which does not distinguish between fat mass and lean muscle. As a result, it remains unclear whether excess fat, lean body mass, or both contribute to increased dementia risk.

Finally, Mendelian randomization relies on the assumption that genetic variants influence disease outcomes only through the risk factor being studied. While the researchers conducted sensitivity analyses to test this assumption, there were indications that some of the extended genetic variants may violate it.

Implications for public health and prevention

Despite these limitations, experts say the findings have clear implications for public health. Vascular dementia, unlike some other forms of cognitive decline, may be particularly amenable to prevention through lifestyle and medical interventions.

“This research reinforces that vascular health is brain health,” Trinh said. “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.”

Richard Terry, DO, MBA, Vice President of Health Science at Lake Erie College of Osteopathic Medicine, echoed this view, noting that obesity itself appears to be an independent risk factor for dementia.

“It’s further exacerbated in patients that have high blood pressure as well, which is often a comorbidity in obese patients,” Terry said. “Along with numerous other studies, this demonstrates that lifestyle management and weight management play a significant role in overall health, lifespan, and dementia risk reduction.”

As dementia rates continue to rise globally, the study adds to growing evidence that preventing cognitive decline may begin decades earlier—by maintaining a healthy weight and keeping blood pressure under control.

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Medicalnewstoday