A recent study has established a clearer connection between obesity and dementia, emphasizing the role of leptin—a hormone that regulates body weight—in improving the health of brain white matter in middle-aged adults.
Recent findings show a stronger association between obesity and dementia.
The research, conducted by The University of Texas Health Science Center at San Antonio (UT Health San Antonio), highlights that higher levels of leptin are linked with healthier brain white matter, which is essential for efficient signaling in the brain of middle-aged individuals.
Claudia Satizabal, PhD, an associate professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, stated, “These results reinforce the established connection between variations in leptin and dementia risk in later life by correlating low levels with changes in white matter structure. This change may signal the early stages of cognitive decline associated with Alzheimer’s disease or vascular dementia.”
Satizabal was the leading author of the study titled, “Leptin bioavailability and markers of brain atrophy and vascular injury in middle age,” which was published on August 12 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Other contributors to this research include members from the Biggs Institute, Tufts Medical Center in Boston, the Framingham Heart Study, Boston University School of Public Health, University of California-Davis, National and Kapodistrian University of Athens, and Columbia University.
Obesity and Alzheimer’s
Alzheimer’s disease is the primary cause of dementia, affecting millions globally, as noted by the study. There is growing evidence that obesity during midlife significantly increases the risk of developing the disease.
This has sparked interest in exploring the mechanisms that connect obesity to Alzheimer’s, which may include vascular, genetic, and metabolic pathways. The study of fatty tissue, or adipose tissue, has provided valuable insights.
Previously thought to be merely an energy storage site, adipose tissue is now recognized as part of the endocrine system. It releases bioactive peptides, referred to as adipokines, which are signaling molecules that play roles in metabolism, energy balance, inflammation, and obesity.
One key adipokine, leptin, is crucial for managing food intake and maintaining energy levels, and it has been linked to various brain functions such as development, the formation of new neurons, and neuroprotection.
Given these influences, leptin may serve as an important link in the chain from obesity to Alzheimer’s disease. Research indicates that higher leptin levels correlate with a reduced risk of developing Alzheimer’s disease and mild cognitive impairment, as well as improved structural brain health in older adults.
However, studies on younger populations have not shown a clear relationship between leptin levels and early signs of brain damage that may precede late-life dementia risk. Therefore, the researchers at UT Health San Antonio sought to explore the connections between leptin and the burdens of neurodegeneration and cerebrovascular issues.
Their investigation focused on how leptin markers relate to cognitive function and brain imaging (MRI) assessments of brain shrinkage and vascular damage in healthy middle-aged adults.
The research involved neuropsychological testing of 2,262 cognitively healthy participants from the Framingham Heart Study, a long-running cardiovascular study in Framingham, Massachusetts, which now collaborates with the National Heart, Lung and Blood Institute and Boston University.
Researchers analyzed levels of leptin, its soluble receptor, and the ratio between them, known as the free leptin index, which indicates leptin availability, using precise immunoassay methods. Cognitive and MRI data were obtained using standardized procedures.
The findings revealed that a higher level of the soluble leptin receptor was linked to lower fractional anisotropy—a measure of brain white matter health—as well as increased indicators of white matter injury. In contrast, a higher free leptin index correlated with improved fractional anisotropy.
These findings were consistent with a follow-up study involving 89 cognitively healthy Hispanic individuals from San Antonio, conducted by MarkVCID, a consortium dedicated to identifying and validating brain biomarkers for vascular contributions to cognitive impairment and dementia (VCID).
In conclusion, the researchers determined that greater leptin availability is linked to better white matter integrity in healthy middle-aged adults, reinforcing the potential protective role of leptin against dementia later in life.
