- New research suggests factors like diabetes, alcohol consumption, and traffic-related pollution may damage a part of the brain associated with dementia.
- The brain area of concern is the last to develop during adolescence and is the first to deteriorate with age.
- The study also explored genetic factors that may influence the effect of modifiable factors on dementia risk.
A comprehensive new study examined the effects of a wide range of modifiable factors and dementia onset.
The study authors had previously identified a “weak spot” in the brain that develops slowly in adolescence, deteriorates early during aging, and has been linked to dementia.
This new study’s findings indicate three factors are most likely to lead to the degradation of this fragile brain region: diabetes, alcohol consumption, and nitrogen dioxide from traffic-related air pollution.
Unique to this new research were two mutations of a lesser-studied genome and an enigmatic blood group called the XG antigen system.
The study is published in Nature Communications.
While the focus of the study is primarily on modifiable factors, the authors felt that the inclusion of potential genetic influences provided a clear overall picture of the health of individuals in the study.
The authors analyzed data — including brain scans — of 39,676 UK Biobank volunteers. They were considered healthier than the general population. Just a few had received a diagnosis of dementia, and participants ranged from 44 to 83 years of age.
The authors measured the effects of 161 modifiable — and a few genetic — factors. Among these were seven changes in the genome that affect this “weak spot.” Some are related to Alzheimer’s disease (AD), Parkinson’s disease (PD), an increased risk of cardiovascular death, and schizophrenia.
Dr. Logan DuBose, a resident physician at George Washington University, not involved in the study, described this weak spot in the brain as the network that develops last and the first to degrade with age.
“The research team identified brain regions that are the first to decline in Alzheimer’s disease, known as ‘higher-order brain regions,’ including the prefrontal cortex, parietal cortex, and temporal cortex, among others,” Dr. DuBose told Medical News Today.
“These regions,” he said, “are associated with long-term memory, executive tasks, working memory, and attention, and they deteriorate as individuals age or in conditions like Alzheimer’s.”
Their last in, first out status “is why they are considered ‘vulnerable’ or ‘fragile,’” Dr. DuBose added, “and the research team closely studies the factors that influence or accelerate the degeneration of these specific fragile brain regions. The researchers’ main goal was to study the things that make these brain regions degrade faster, so they can inform us about ways to avoid certain risk factors and preserve brain health.”
Dr. Claire Sexton, senior director of scientific programs and outreach at the Alzheimer’s Association, not involved in the study, commented on the three factors identified by the researchers for MNT (diabetes, alcohol intake, and air pollution).
“These are well-known risk factors for dementia, so their association with a vulnerable brain network seems very plausible,” Dr. Sexton said.
The authors say that their investigation of the X chromosome revealed their strongest genetic finding in a peculiar region shared by both sex chromosomes.
“The XG antigen system is another gene that researchers examined to determine if it made people more or less susceptible to accelerated degeneration of their fragile brain regions,” Dr. DuBose said.
“Interestingly, they discovered that individuals with a specific type of XG gene could be more affected by air pollution found in the air they breathe. This was found to be a major factor contributing to damage in fragile brain areas,” Dr. DuBose noted.
He considered this finding to be significant, he said, “as it could establish a link between environmental factors such as living in high-traffic areas or large cities with lots of pollution and increased risk of damage to fragile brain regions.”
For Dr. DuBose, such insights suggest a genetic influence on a person’s susceptibility to known risk factors.
“This insight is crucial, especially as technology advances our ability to know a person’s genetic predispositions. Knowing a person’s genes and the associated risks those genes cause allows healthcare providers and patients to intervene early, potentially slowing disease progression or damage that otherwise would be more accelerated.”
— Dr. Logan DuBose, physician
Dr. DuBose pointed out that the study also found associations between genetic clusters and modifiable risk factors, including alcohol intake and diabetes.
The authors pointed out another interesting, for now unexplained finding: one of the novel genetic mutations they observed on the X chromosome was associated with early life and socioeconomic factors, including:
- their number of siblings
- whether they were breast-fed as an infant
- whether their mother smoked when pregnant
The current study builds on evidence that has shown how multiple risk factors may contribute to dementia onset.
Still, Dr. Sexton called for more research in representative populations that may replicate and confirm the study’s findings.
She highlighted, however, the Alzheimer’s Association’s two-year trial to evaluate “whether lifestyle interventions that simultaneously target multiple risk factors can protect cognitive function in older adults at increased risk for cognitive decline.”
The study is called the U.S. Pointer Study, or U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk. It is the first such study of a large, representative group of Americans.
In the study, more than 2,000 volunteer older adults deemed at increased risk of cognitive decline are being followed for two years.
“Nearly 30% of current participants are from populations historically underrepresented in Alzheimer’s/dementia research. Data/results are expected in 2025,” Dr. Sexton said.
