Scientists have long recognized that conditions affecting the body can also influence the brain. Issues such as obesity, high blood pressure and insulin resistance place strain on the body's metabolic and vascular systems. Over time, this buildup of stress can accelerate cognitive decline and raise the likelihood of Alzheimer's disease.
Researchers at Arizona State University, working with partners at several institutions, now report that these effects may appear much earlier than expected. In young adults with obesity, the team identified biological markers linked to inflammation, liver strain and early injury to brain cells. These small but measurable shifts resemble patterns seen in older adults with cognitive impairment.
The study uncovered another important finding. Many of the young adults showed unusually low blood levels of choline, a nutrient essential for supporting liver health, regulating inflammation and protecting long-term brain function.
"This research adds to the growing evidence that choline is a valuable marker of metabolic and brain dysfunction -- and reinforces the importance of sufficient daily intake, as it is essential for human health," says Ramon Velazquez. "Several new reports published this month further link reduced blood choline levels to behavioral changes, including anxiety and memory impairment, as well as broader metabolic dysfunction."
Velazquez leads the study as part of the ASU-Banner Neurodegenerative Disease Research Center, working with colleagues from the ASU School of Life Sciences, Banner Sun Health Research Institute and Mayo Clinic, AZ. The findings were published in Aging and Disease.
Obesity's Early Impact on Brain Biology
Although obesity is widely known to increase the risk of chronic conditions such as heart disease and type 2 diabetes, this study suggests its influence on the brain may develop much earlier. The researchers measured elevated levels of inflammation-promoting proteins and enzymes that indicate liver stress. They also detected higher levels of neurofilament light chain (NfL), a protein released when neurons are damaged. NfL was linked to low blood choline levels in these young adults, even though no behavioral changes would typically be expected at this age.
NfL has emerged as an important early signal of neurodegeneration. It is found at elevated levels in people with mild cognitive impairment and Alzheimer's disease. Observing these markers in young adults is significant and suggests that obesity may create measurable effects in the brain well before symptoms appear.
The results support the idea that inflammation, metabolic strain and early neuronal changes may be connected in a way that starts much earlier in life than once believed.
Choline's Influence on Brain and Metabolic Health
A central aspect of the study involves choline, a nutrient essential for cell-membrane structure, inflammation control, liver function and the production of acetylcholine, a neurotransmitter important for memory. Participants with obesity had substantially lower levels of circulating choline, and these reductions corresponded with stronger signs of inflammation, insulin resistance, liver-enzyme elevation and NfL.
Although the liver produces some choline, most must come from food. Rich dietary sources include eggs, poultry, fish, beans and cruciferous vegetables such as broccoli, cauliflower and brussels sprouts. The researchers also observed that women in the study had lower choline levels than men, a notable finding because women experience higher rates of cognitive aging and Alzheimer's disease.
National nutrition surveys show that many Americans do not meet recommended choline intake, especially teenagers and young adults. Since choline supports the brain and liver, long-term shortages may heighten vulnerability to metabolic stress and intensify the effect obesity has on the brain.
"Most people don't realize they aren't getting enough choline," said Wendy Winslow, first co-author. "Adding choline-rich foods to your routine can help reduce inflammation and support both your body and brain as you age."
Nutrient Considerations for New Weight-Loss Drugs
Modern weight-loss drugs have transformed obesity treatment because of their effectiveness in reducing weight and improving metabolic and cardiovascular health. However, the appetite-suppressing effects of GLP-1 medications significantly reduce food intake. This may lead to inadequate consumption of choline and other key nutrients. The authors note the need for future studies to explore whether pairing GLP-1 therapies with adequate dietary choline can help maintain metabolic resilience and overall health.
Study Design and Key Measurements
The research involved 30 adults in their 20s and 30s, split evenly between those with obesity and those of healthy weight. Each participant provided a fasting blood sample. The samples were analyzed for circulating choline, inflammatory cytokines, insulin, glucose, liver enzymes, additional metabolic measures and NfL.
Comparisons between groups revealed consistent patterns: lower choline levels, greater inflammation, metabolic stress and signs of neuronal damage in young adults with obesity. To understand how these findings relate to brain aging, the team compared their results with data from older adults diagnosed with mild cognitive impairment or Alzheimer's disease.
The same pairing of low choline and high NfL was found in both young and older adults. This suggests that biological changes associated with Alzheimer's may begin many years before symptoms arise, especially in people experiencing metabolic stress or obesity.
Early Indicators of Long-Term Cognitive Risk
Overall, the study highlights a strong link among obesity, inflammation, choline status and early neuronal stress. This combination may help explain why metabolic disorders increase the likelihood of cognitive decline later in life.
Although the study does not establish causation, it reveals a group of biomarkers that closely resemble those found in older adults with cognitive impairment. The results also align with earlier rodent studies showing that inadequate choline intake in mice can lead to obesity, metabolic problems and increased Alzheimer's disease pathogenesis.
"Our results suggest that, in young adults, good metabolic health and adequate choline contribute to neuronal health, laying the groundwork for healthy aging," says Jessica Judd, co-author of the study.
Ongoing research will continue exploring how early metabolic stress may shape long-term risk for neurodegenerative disease and could eventually inform new strategies to protect brain health across the lifespan.
