Current estimates are that around 36 million people suffer from Alzheimer’s disease or related dementias, and there are no approved medications to prevent the progression of this mind wasting debilitating disease which is the fourth leading cause of death around the globe.

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Dementia researchers have looked into a variety of possible causes for the disease, from genetics to traumatic brain injuries. But one group, led by genetic epidemiologist Dr. Shaoyong Su, is looking into a surprising research area: high blood pressure in childhood.

Prior research has established high cholesterol and blood pressure, as well as obesity and aging, as risk factors for developing dementia. But Su and his colleagues at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University decided to focus on whether higher or rapidly increasing blood pressure during childhood can cause vascular damage, leading to restricted blood flow and even brain cell death.

“Dementia is not a normal part of aging, and once it begins you can’t reverse it,” Su said in a news release. “It typically surfaces at about age 65 or older, but we think the problem really starts much earlier.”

The Link Between Dementia and High Blood Pressure

According to the World Health Organization (WHO), around 50 million people worldwide are affected by dementia, and around 10 million new cases arise each year. The increase of risk factors for dementia, particularly in children, makes the need for early diagnosis and risk screening crucial, says Su.

To fill this need, Su and fellow researchers Dr. Catherine Davis, a clinical health psychologist at the Georgia Prevention Institute, and Dr. Nathan Yanasak, a magnetic resonance imaging scientist in the MCG Department of Radiology and Imaging, are conducting a study on lifetime data from 600 people. The study sample represents a roughly equal number of men and women of various races who were entering midlife and on whom the researchers had childhood data.

The participants were at an average of 40 years old at the time of the study. The researchers collected data on them over the course of 23 years, including ambulatory blood pressure, arterial stiffness, and other measures of chronic stress and lifestyle. Reflecting the general population, about one third of the study group now have high blood pressure.

Su and his team are conducting brain imaging to examine other relevant risk factors, like cerebral blood flow and cognitive testing. A few of their subjects have shown symptoms of arterial stiffness and atherosclerosis—an arterial disease characterized by fatty deposits forming on arterial walls—and Su hopes to answer whether these factors are associated with unhealthy structural and functional changes in the brain.

“First we have to know exactly what is happening,” Yanasak explained in the news release. “Once we know what is happening, we can start searching for solutions.”

“We will be able to look at associations between their cardiovascular measures over time and the current status of their cognitive ability, their cerebral blood flow and brain structure,” Davis added.

Some of their research has already shown that an elevated blood pressure—whether from childhood trauma, obesity or lifestyle factors like diet and inactivity—can affect blood flow and alter some of the delicate architecture of the brain.

According to Su, it’s not instantaneous damage, but rather progressive problems that are the real danger. Other studies have already shown a connection between hypertension in middle age (or even as early as your 30s) and cognitive decline in old age.

The researchers are using a variety of tests to get their results, including arterial spin labeling and diffusion tensor imaging. Arterial spin labeling, which is regularly used to rapidly assess brain blood flow in stroke patients, measures the amount of blood flowing in the brains of study participants. By manipulating the magnetic properties of blood, the scanner enables the measures of blood flow through minuscule capillaries feeding brain tissue.

Diffusion tensor imaging, comparatively, allows a glimpse at the brain’s nerve fibers, or axons, which enable communication from neurons to muscle cells, organs, and other neurons. This advanced form of scanning uses the natural flow of water to examine the integrity of these neural fibers. According to Yanasak, subtle changes in this tissue, not normally detectable by a standard MRI, are an early warning sign that the vasculature of the brain is being impacted by high blood pressure.

As part of the study, participants are also questioned on lifestyle habits, such as physical activity levels and the use of alcohol and tobacco products. Su and his team are looking into whether unhealthy environmental factors correlate with high blood pressure and worsen any impact on the brain and cognition.

“We can see whether their lifestyle can influence or modify the relationship between blood pressure and brain cognitive function,” Su said.

Childhood Trauma, Blood Pressure and the Brain

According to Su, those who experienced multiple traumatic events in childhood, from emotional and sexual abuse to neglect, had higher blood pressures as young adults than their peers. The difference of 10 points in the systolic pressure—the top number denoting pressure while the heart is contracting—by early adulthood puts these young people at higher risk for hypertension and coronary artery disease by middle or old age.

The stress levels of participants are also being assessed through questions about stress in life, family or work problems, as well as socioeconomic status and adverse childhood events. According to Su, traumatic childhood experiences, like sexual assault or abandonment, can result in actual structural changes to a child’s developing brain and put them at increased risk for unhealthy habits like smoking and other substance abuse.

Hoping to expand their research, Su and his team also aim to investigate whether ethnicity and sex are factors in providing protection against or increasing the effects of unhealthy associations. Some associations, such as black men tending to have higher blood pressure earlier in life and a significantly higher nighttime blood pressure, have already been established by past research.

According to Su, it’s important to determine which factors present early in life can influence risk for developing dementia, and to determine from them the best strategies and times for preventative intervention.

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The exact causes behind dementia are varied and at times unclear. We know that genetic factors — like carrying the APOE4 gene — can have an impact on a person’s risk of developing Alzheimer’s, as can lifestyle or environmental factors like diet, exercise and exposure to air pollution. And a new study adds to the growing evidence that weight and obesity may also contribute to a person’s dementia risk.

The study, conducted by researchers at the University of Oxford in the U.K., was published in Neurology and examined over one million women living in the U.K.

Researchers have known from past studies that a larger waist size, and metabolic issues like diabetes, are linked to neurodegenerative diseases like Alzheimer’s and dementia. But the scientists working on the latest study wanted to examine this connection further.

The goal was to “help determine whether midlife obesity is a cause of dementia” rather than just a correlation. Plus, the researchers wanted to understand why there has appeared to be a link between the development of dementia and low body mass index (BMI), low calorie intake and physical inactivity. Does the dementia cause a person to lose weight and become inactive, or is it the other way around?

Investigating Obesity, BMI and Dementia
The researchers followed over one million women, who had a mean age of 56, for 15 years — from 1996 to 2001. They measured height, weight, caloric intake and levels of physical inactivity. In 2017, the researchers followed up with the women by taking note of their National Health Service records, marking down hospitalizations and any mentions of dementia.

They found that women who were considered obese — with a body mass index (BMI) over 30 — were 21 percent more likely to develop dementia compared to women with a healthier BMI of 20-24.9.

2.2 percent of the women with obesity ended up with dementia long-term, but only 1.7 percent of the women with a healthy BMI did. This suggests that obesity likely contributes to the development of dementia.

Interestingly, however, the researchers found that while the other three factors investigated — low caloric intake, low BMI and inactivity — were associated with a higher dementia risk earlier on in the women’s lives, they ultimately did not appear to contribute to the risk over the long-term.

“Some previous studies have suggested poor diet or a lack of exercise may increase a person’s risk of dementia,” Sarah Floud, lead researcher on the study, said. “However, our study found these factors are not linked to the long-term risk of dementia. The short-term links between dementia, inactivity and low calorie intake are likely to be the result of the earliest signs of the disease, before symptoms start to show.”

However, that’s left to be debated — as many experts and past researchers have argued that a person’s Alzheimer’s or dementia risk is greatly reduced if they eat a healthy diet and exercise. One recent study suggested that up to one-third of dementia cases could be prevented with lifestyle changes.

Floud does agree, however, that obesity is likely tied to a greater dementia risk. “On the other hand, obesity in midlife was linked with dementia 15 or more years later,” she said. “Obesity is a well-established risk factor for cerebrovascular disease. Cerebrovascular disease contributes to dementia later in life.”

The relationship between the metabolic system and dementia is complex and still being investigated by researchers.

However, many experts advocate for their patients to stay active, whether or not they have a risk of developing Alzheimer’s. Exercise has been shown to be the single most effective preventive tool against the disease.

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Sarah Floud, Ph.D., of the Nuffield Department of Population Health at the University of Oxford in the United Kingdom, is the lead author of the study.

As Floud and her colleagues explain in their paper, some previous studies have found an association between a low body mass index (BMI) and the likelihood of receiving a diagnosis of dementia within the next 5–10 years.

Other studies that lasted a decade or less have also linked poor diet and lack of exercise with the incidence of dementia.

However, all of the above may be the result of reverse causality, meaning that they may be consequences, rather than causes, of dementia. This situation could well be possible, explain the authors, because dementia typically affects cognition a decade before the person formally receives a diagnosis.

During this preclinical stage, the condition can slowly but gradually affect behavior, impair mental and physical activity, reduce the intake of food and calories, and cause weight loss.

Furthermore, explain the authors, some recent meta-analyses have pointed out that although in the short term, a low BMI may be associated with dementia as a result of reverse causality, over a longer period, obesity is positively associated with dementia.

Either way, prospective studies over longer periods are necessary to settle the matter of how BMI connects to dementia risk. Floud and her team set out to do exactly this.

Their findings appear in the journal Neurology.

Studying diet, inactivity, BMI, and dementia

The team examined 1,136,846 women in the U.K. They had an average age of 56 years and were free of dementia at the start of the study, between 1996 and 2001.

The women gave information about their height, weight, calorie intake, and physical activity, and the researchers clinically followed them until 2017 through the National Health Service records. These records also noted any hospital admissions for dementia. 

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For their study, the scientists considered a BMI of 20–24.9 as “desirable,” 25–29.9 as overweight, and 30 and over as obese. They classified women who exercised less than once a week as inactive and those who exercised at least once weekly as active.

Using Cox regression models, the team calculated the links between BMI and dementia incidence over the follow-up period, adjusting for age, height, education, smoking, alcohol intake, use of menopausal hormones, residential area, and area deprivation.

Midlife obesity linked with 21% higher risk

Over the study period, 89% of the participants had no mention of dementia in their health records. At 15 years after the start of the study, 18,695 women had received a dementia diagnosis.

Women who had obesity at the beginning of the study were 21% more likely to develop dementia than women who had a “desirable” BMI.

More specifically, 2.2% of the women with obesity went on to develop dementia in the long term, compared with 1.7% of those with a healthy BMI.

Although the findings revealed that low calorie intake and a lack of physical activity had a link with higher dementia risk in the first decade of the study, these associations gradually faded after that period, and neither calorie intake nor inactivity had a significant association with dementia risk.

Floud comments on the findings, saying, “Some previous studies have suggested poor diet or a lack of exercise may increase a person’s risk of dementia.”

“However, our study found these factors are not linked to the long-term risk of dementia. […] The short-term links between dementia, inactivity, and low calorie intake are likely to be the result of the earliest signs of the disease, before symptoms start to show,” she emphasizes.

The study is limited by the fact that it only involved women, which means that the findings may not apply to men.

The authors of a linked editorial also mention “the absence of time-dependent dynamic analyses of BMI […], crude measurement of dietary habits, and residual confounding” as study limitations.

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