Poor metabolism associated with poor brain health

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Metabolism and brain health may be more interconnected than first thought. Jimena Roquero/Stoxy
  • Researchers are investigating the link between metabolic profile and brain health.
  • Factors such as high blood pressure and a high basal metabolic rate (BMR) are associated with poorer brain health.
  • The researchers note that further studies are needed to determine causality.

According to the World Health Organization over 55 million people live with dementia worldwide, with 10 million new cases diagnosed each year.

Studies show that the brain undergoes functional and structural changes years before the onset of cognitive impairment.

Other studies shows that metabolic factors such as diabetes, dyslipidemia (blood lipid levels that are too high or low), and high blood pressure are associated with cognitive decline and dementia.

one study found that patients aged 60 and older with metabolic risk factors were 11.48 times more likely to develop Alzheimer’s disease than those without.

Investigating the relationship between metabolic risk factors and dementia may support preventive approaches based on metabolic risk profiles.

Recently, researchers investigated the relationship between metabolic biomarkers and brain health captured through brain imaging data.

They found that metabolic profiles were associated with neuroimaging features that indicated cognitive decline and increased risk of dementia.

The study was published in Diabetes, obesity and metabolism.

For the purpose of the study, the researchers analyzed data from 26,239 individuals from the UK Biobank who did not suffer from dementia and stroke at recruitment. Participants were aged between 37 and 73 years at recruitment, and 52% were female.

The researchers examined the participants’ brain MRI data, including:

  • total brain volume (TBV)
  • gray matter volume (GMV)
  • volume of white matter hyperintensity (WMH).
  • hippocampal volume (HV)
  • iron deposition

Of these brain MRI measures, lower TBVlower GBV and larger WMV volume are associated with brain damage and loss of function.

Meanwhile, greater iron deposition is associated with a greater risk of Alzheimer’s disease, the most common form of dementia. Reduced HV is also associated with poorer memory, verbal learning, processing speed, and executive function.

The researchers evaluated the brain images for a number of biomarkers, including:

  • cholesterol levels
  • levels of inflammation
  • kidney function
  • liver function
  • Body Mass Index (BMI)
  • Basal Metabolic Rate (BMR) – the number of calories burned at rest
  • Blood Pressure
  • 25(OH)D levels, which is a measure of vitamin D

They found that younger age, higher level of education, never having smoked, greater number of working hours and higher level of physical exercise were associated with greater HV and fewer brain lesions.

They also noted that levels of iron deposition tended to increase with age and were higher among those smokers and ex-smokers, those with higher levels of education, more work hours, and higher levels of vigorous exercise. .

In addition, the researchers found that high triglycerides, high BMI, poor liver and kidney function, and high levels of inflammation were associated with the most adverse brain outcomes.

High triglycerides and liver dysfunction, in particular, were associated with the highest levels of iron deposition, brain lesions, and GMV loss.

The researchers noted that higher BMR was associated with more iron deposition, lower GMV, and lower HV than obesity.

They also noted that lower vitamin D levels were associated with more brain lesions and lower TBV and GMV.

When asked how iron accumulates in the brain, Dr. Russell H. Swerdlow, director of the University of Kansas Alzheimer’s Disease Research Center, University of Kansas School of Medicine, who was not involved in the study, said Medical News Today:

“[The brain needs iron] to build certain structures called “respiratory chain enzymes” [proteins that play a role in cell metabolism] which are defective in Alzheimer’s. If a person cannot properly form their respiratory chain enzymes, iron levels will begin to rise.

Dr. Mikhail Kolonin, professor and director of the Center for Metabolic and Degenerative Diseases at the University of Texas, who was also not involved in the study, added:

“Normally, the blood-brain barrier (BBB) ​​limits the access of iron to brain cells. Recurrent microbleeds may be one explanation for the increased iron accumulation occurring in old age. However, chronic aging-related metabolic and inflammatory dysfunction poses a threat [cells that form the BBB]leading to increased iron entry into the brain may be more important.’

“Iron accumulation, oxidative damage [from excessive iron accumulation] further promotes cell death, the processes that underlie all neurodegenerative diseases.
— Dr. Mikhail Kolonin

The researchers noted that most of their findings were consistent with previous research. However, Dr. Colonin noted that the study’s findings on BMR were surprising.

“Basal metabolic rate decreases with age and athletes are known to have a significantly higher basal metabolic rate, making the study’s findings counterintuitive. It is clear that basal metabolic rate can be modulated by both health-promoting and pathogenic processes,” he said.

“Further research will be needed to identify markers more selectively predictive of risk for neurophysiological dysfunction,” he added.

The researchers note that while BMR is essential for neuronal function, higher BMR can promote oxidative stress if not adequately balanced by antioxidants in the body. However, they agreed that further studies are needed to investigate this link.

The researchers concluded that metabolic markers such as BMR and BP may provide valuable insight into the development of dementia.

When asked about the study’s limitations, Dr. Colonin said:

One limitation is the exclusion of individuals with a history of dementia or stroke. Useful clinical information can be expected from a separate analysis including this group. Another issue is that the UK Biobank cohort may not reflect the general population as it is limited to participants of white British ancestry and is subject to healthy volunteer bias. Therefore, these findings should be reevaluated in independent datasets containing other ethnic and socioeconomic groups.

Dr. Swerlow added that while the study found an association between metabolic measures and brain imaging data suggestive of cognitive impairment, it did not address causality.

“The best way to maintain a healthy metabolism is to avoid gaining excess weight through a healthy diet and physical activity. Indeed, exercise is perhaps the most effective approach to Alzheimer’s disease prevention,” said Dr. Kolonin.

“The mechanisms of its effect are not fully understood. However, they are likely to include lowering blood sugar levels and normalizing vascular function. This probably results in an improvement of the BBB, [and thus a decreased] risk of vascular dementia and other neurodegenerative diseases,” he added.

Dr. Swerdlow agreed that a healthy lifestyle is key to improving metabolic health. He said: “Things like constant overeating, sedentary lifestyles, smoking, walking with uncontrolled hypertension and things like that certainly seem to have a negative effect on metabolism.”

“Although there is still an ongoing debate, tantalizing data—including some generated at our Alzheimer’s Disease Research Center—suggest doing things that benefit metabolism and avoiding things that harm metabolism. may reduce the risk of dementia.’
— Dr. Russell H. Swerdlow

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