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SAN ANTONIO — The same hormone that keeps people from overeating and gaining weight may also protect older adults from developing Alzheimer’s disease. Researchers have uncovered a potential link between leptin, a hormone involved in appetite regulation, and brain health in middle-aged adults.
The research, published in the journal Alzheimer’s & Dementia, suggests that higher levels of bioavailable leptin may have a connection with better preservation of white matter in the brain, potentially reducing the risk of dementia later in life.
Leptin, often referred to as the “satiety hormone,” is mainly known for its role in regulating hunger and metabolism. Simply put, this hormone is released to keep the amount of energy your body uses and how much food you eat in balance.
However, this new study is revealing its potential neuroprotective properties, particularly in maintaining the integrity of white matter – the brain tissue responsible for connecting different regions and boosting communication between them.
“The findings support the known role of leptin variations in late-life dementia risk by relating its deficiency with changes in white matter structure, which is an early event in the process of cognitive impairment due to Alzheimer’s disease or vascular dementia,” notes Claudia Satizabal, PhD, an associate professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, in a media release.
The study authors examined 2,262 cognitively healthy middle-aged adults with an average age of 40. Of these participants, 2,028 also underwent brain MRI scans. The researchers measured levels of leptin, its soluble receptor, and calculated a measure called the free leptin index (FLI), which indicates how much leptin is actually available for the body to use.
Using advanced imaging techniques, the team assessed various markers of brain health, including total brain volume, gray matter volume, and white matter integrity. They found that individuals with higher leptin bioavailability — which the team determined through the presence of lower levels of the soluble leptin receptor and higher FLI — displayed better white matter integrity.
White matter integrity is crucial for cognitive function, as it allows different parts of the brain to communicate efficiently. Think of it as the brain’s information superhighway – when it’s in good condition, information travels quickly and accurately between brain regions. When white matter starts to deteriorate, it can cause cognitive decline and various forms of dementia, including Alzheimer’s disease.
Interestingly, the study did not find significant links between leptin bioavailability and cognitive test scores or overall brain volumes. However, when the researchers looked at men specifically, they found that higher leptin bioavailability had a connection to better performance in tests of visuospatial skills and executive function.
The findings were partially replicated in a smaller, more diverse sample of 89 older Mexican American adults, providing additional support for the relationship between leptin and brain health across different populations.
This research is particularly noteworthy because it focuses on cognitively healthy middle-aged adults. By identifying potential markers of brain health in this age group, researchers may be able to develop strategies to prevent cognitive decline before it’s too late.
This could be especially beneficial for individuals with excess belly fat, as the study found stronger associations between leptin bioavailability and white matter integrity among overweight and obese individuals.
Paper Summary
Methodology
The researchers used blood samples to measure leptin and its soluble receptor levels. They then calculated the free leptin index to estimate leptin bioavailability. Participants underwent cognitive tests and brain MRI scans. The MRI data was analyzed using advanced techniques to assess white matter integrity, including measures like fractional anisotropy, free water, and peak width of skeletonized mean diffusivity.
Key Results
Higher leptin bioavailability was associated with better white matter integrity, as indicated by higher fractional anisotropy and lower free water and peak width of skeletonized mean diffusivity. In men, higher leptin bioavailability was linked to better performance in visuospatial and executive function tests. The association between leptin receptor levels and white matter integrity was replicated in a smaller, diverse sample.
Study Limitations
The study’s cross-sectional design means it can’t establish cause-and-effect relationships. There was an average 8-year gap between blood sample collection and brain imaging, which could have introduced some inconsistencies. The study also primarily included non-Hispanic White participants, limiting its generalizability to other populations.
Discussion & Takeaways
The findings support the idea that leptin may play a neuroprotective role in the brain. By linking leptin bioavailability to white matter integrity in middle-aged adults, the study suggests that leptin might influence brain health long before cognitive symptoms appear. This opens up possibilities for early intervention strategies to maintain cognitive health as people age.
Funding & Disclosures
The study was funded by various institutes within the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. Some authors reported consulting for pharmaceutical companies, but these relationships were not directly related to the study’s conduct or results.
