Obesity in midlife may cause vascular dementia later in life by raising blood pressure over decades and quietly damaging brain vessels, according to new research released Thursday.
The danger could be significant. Having a higher body mass index increases the risk of vascular dementia by roughly 50 to 60 percent, according to the study, published in the Journal of Clinical Endocrinology & Metabolism. An association between obesity and dementia has long been the subject of study, and the new research strongly indicates there is indeed a link.
“We add a layer of evidence that suggests causality,” said Ruth Frikke-Schmidt, who was the study’s lead author and is a professor and chief physician at Copenhagen University Hospital Rigshospitalet and the University of Copenhagen. “For public health, this is an important message.”
More than 50 million people globally — 7 million of them Americans — live with dementia. Vascular dementia is the second most common form. It is caused by cerebrovascular disease, which shares many of the same risk factors as cardiovascular disease.
It is caused by problems with blood flow to the brain, which can happen after a stroke or when blood vessels are damaged over time from conditions like high blood pressure, diabetes or hardening of the arteries.
Over time the brain is unable to compensate. Unlike Alzheimer’s disease where memory tends to go first, with vascular dementia the loss of executive function — planning, organizing, decision-making — precedes memory loss. Loss of function is last.
The decline tends to happen in noticeable steps of stable periods interrupted by sudden drops in function, as opposed to the slower progression of Alzheimer’s disease, dementia experts said.
A substantial portion of the increased risk of vascular dementia — 18 to 25 percent — was explained by high blood pressure, the study found.
What makes the study notable is the research method used, which mimics a randomized clinical trial — the gold standard in science — and is called Mendelian randomization, dementia experts said. The team analyzed naturally occurring genetic differences that influence body weight.
“It’s like nature’s own randomized clinical trial, because the genes themselves are like randomized groups,” said Cyrus A. Raji, neuroradiologist, associate professor and principal investigator in the Neuroimaging Labs Research Center at Mallinckrodt Institute of Radiology at Washington University School of Medicine
Raji, who researches obesity and dementia but was not involved in the study, noted genes are assigned at conception. “They aren’t influenced by lifestyle, education or illness later in life,” he said.
The study shows that genetic variants that raise body weight also raise dementia risk but not by themselves, he said. “But also, by way of high blood pressure.”
On a scale of 1 to 10, Raji said he would place the study at an eight in terms of importance.
“The only reason I wouldn’t give it a 10 is because it didn’t quite include the widest range of diverse populations to best understand the full range of these relationships,” he said.
Researchers analyzed blood samples from three biobanks — two in Denmark and one in the United Kingdom. All of the participants were White, a limitation the study authors acknowledged.
They used diagnostic codes to track who was and wasn’t eventually diagnosed with vascular dementia and then linking those outcomes to gene variants associated with high body mass index.
Of the 126,655 blood samples taken over the course of 27 years as part of two Danish population health studies, 2,260 developed vascular-related dementia, 2,111 developed Alzheimer’s disease, and 14,188 developed ischemic heart disease. And of the 377,755 people who were part of UK Biobank, 3,317 developed vascular-related dementia, 2,215 developed Alzheimer’s disease, and 45,539 developed ischemic heart disease.
“The public health message is clear. Controlling blood pressure in people with obesity may actually help prevent dementia,” said John N. Mafi, an internist and associate professor of medicine at UCLA’s David Geffen School of Medicine who was not involved in the study. “It’s a huge problem, and yet, it’s not 100 percent clear what proportion of it is preventable.”
The current toolbox for reducing dementia risk is limited, and there’s no ways to prevent it outside of lifestyle changes. In 2024, the Lancet found that about 45 percent of dementia cases could potentially be delayed or reduced. It suggested people in midlife stop smoking, stop using alcohol excessively, get better sleep, exercise and maintain ideal blood pressure, cholesterol and blood sugar.
But the question of whether obesity causes dementia has been unclear, dementia experts said, because of confounding factors. One of the first symptoms of dementia — before ever being diagnosed — can be weight loss from not eating, experts said.
“In observational research, we get fooled time and time again,” said Mafi, who also studies dementia and cares for patients with the condition. While the study using genetic variants “is not perfect,” he said, “it is substantive. It’s a real step up in our knowledge.”
Another limitation of the study was the use of medical diagnostic codes, which often don’t reflect the full scope of the health situation. In the United States, “there’s a big inequality in getting the codes,” he said, pointing to research from the University of Michiganthat showed Black patients with the same cognition as White patients got the codes — meaning the diagnosis — later. “So, you always have to take that with a grain of salt.”
The question remains if obesity is treated aggressively, will it prevent dementia down the line, he said. The ultimate proof of that, he said, would be a randomized controlled trial with a diverse pool of people. Still, he said the evidence was strong enough that he would discuss dementia prevention as an added benefit of weight loss with patients.
“I’m probably going to start telling my patients, ‘There may, in fact, be a link between your weight and vascular dementia, so that’s another motivation for us to focus on weight loss,’” he said.
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