New research suggests that factors such as diabetes, alcohol consumption, and traffic-related pollution may damage a part of the brain associated with dementia. This area of the brain, known as the “weak spot,” is the last to develop during adolescence and the first to deteriorate with age. The study explored genetic factors that may influence the effect of modifiable factors on dementia risk, identifying three factors that are most likely to lead to the degradation of this fragile brain region: diabetes, alcohol consumption, and nitrogen dioxide from traffic-related air pollution. The study also examined two mutations of a lesser-studied genome and an enigmatic blood group called the XG antigen system.
Published in Nature Communications, the comprehensive study analyzed data from 39,676 UK Biobank volunteers, considered healthier than the general population. The participants ranged in age from 44 to 83 and included individuals who had received a diagnosis of dementia. The authors measured the effects of 161 modifiable and genetic factors, including seven changes in the genome that affect the vulnerable brain region related to Alzheimer’s disease, Parkinson’s disease, cardiovascular death, and schizophrenia. These findings provide insights into factors that may accelerate the degeneration of specific fragile brain regions and inform strategies for preserving brain health.
Dr. Logan DuBose, a resident physician at George Washington University, described the weak spot in the brain as the network that develops last and the first to degrade with age. This brain region is associated with long-term memory, executive tasks, working memory, attention, and deteriorates with aging and conditions like Alzheimer’s disease. The study aimed to identify factors that influence the degeneration of these regions to inform ways to avoid risk factors and preserve brain health. The three factors identified by the researchers – diabetes, alcohol intake, and air pollution – are well-known risk factors for dementia and were associated with the vulnerable brain network.
The study also revealed intriguing genetic findings, including associations between the X chromosome and susceptibility to accelerated degeneration of fragile brain regions. Individuals with a specific XG gene were found to be more affected by air pollution, leading to an increased risk of damage in these areas. Understanding genetic predispositions and associated risks can allow for early interventions to potentially slow disease progression or prevent accelerated damage. The study also highlighted associations between genetic clusters and modifiable risk factors, pointing to the potential impact of genetic influences on a person’s sensitivity to known risk factors.
While the findings of the study provide valuable insights into the connections between modifiable and genetic factors and their impact on dementia risk, further research is needed to replicate and confirm these results in representative populations. The Alzheimer’s Association is conducting a two-year trial called the U.S. Pointer Study to evaluate whether lifestyle interventions targeting multiple risk factors can protect cognitive function in older adults at increased risk for cognitive decline. The study involves over 2,000 volunteer older adults and aims to assess the impact of lifestyle interventions on cognitive health, with results expected in 2025. This research underscores the importance of understanding the complex interplay of genetic and modifiable factors in dementia onset and potential strategies for prevention.
