How a Hormone Could Protect Your Brain: New Research Links Leptin to Lower Dementia Risk

leptin brain health dementia risk

Leptin Hormone Linked to Better Brain Health and Lower Dementia Risk

A hormone that plays a pivotal role in weight regulation is crucial for effective brain signal transmission.

New research strengthens the connection between obesity and dementia.

A study by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has revealed that elevated levels of leptin, a hormone integral to maintaining body weight, are linked to improved transmission in brain white matter among middle-aged individuals.

“These findings bolster the established connection between leptin variability and dementia risk in later life by associating leptin deficiency with alterations in white matter structure—an early marker of cognitive decline, linked to Alzheimer’s disease or vascular dementia,” stated Claudia Satizabal, PhD, associate professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio.

Satizabal spearheaded this research, which was recently featured in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Contributing authors hail 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, the foremost cause of dementia, affects millions globally. An expanding body of research suggests that midlife obesity significantly contributes to the likelihood of developing this condition.

This has spurred increased interest in understanding the intricate mechanisms that link obesity to Alzheimer’s. These pathways appear to involve vascular, genetic, and metabolic factors, with research into adipose (fat) tissue shedding new light on the subject.

Previously regarded as merely a storage site for energy, adipose tissue is now recognized as part of the endocrine system. It secretes bioactive peptides known as adipokines—cell-signaling molecules that influence the body’s energy balance, inflammation, and obesity.

Leptin, a key adipokine, governs central control of food intake and energy regulation. Additionally, it plays a role in numerous neurophysiological processes, such as brain development, neurogenesis, and neuroprotection.

Given these functions, leptin is seen as a plausible link between obesity and Alzheimer’s disease. Research suggests that higher levels of leptin correlate with a reduced risk of developing Alzheimer’s and mild cognitive impairment, as well as better structural brain health in older adults.

However, studies of younger populations have not yet found any connection between leptin and the early signs of brain deterioration that precede late-life dementia. The researchers at UT Health San Antonio aimed to explore the relationship between leptin and neurodegenerative and cerebrovascular markers.

Specifically, they examined the associations between leptin levels and cognitive performance, as well as MRI-based indicators of brain atrophy and vascular injury in healthy middle-aged individuals.

leptin brain health dementia risk: New Insights on Leptin and Brain Function

The researchers conducted neuropsychological assessments on 2,262 cognitively healthy participants from the Framingham Heart Study—a long-term cardiovascular cohort study in Framingham, Massachusetts, now in its third generation and overseen by the National Heart, Lung, and Blood Institute in collaboration with Boston University.

They measured leptin concentrations, its soluble receptor, and the ratio between the two, known as the free leptin index, which indicates leptin bioavailability. Enzyme-linked immunosorbent assays were used for these measurements. Cognitive and MRI assessments followed standardized protocols.

The findings revealed that higher concentrations of the soluble leptin receptor were associated with reduced fractional anisotropy, a biomarker of brain white matter integrity, and peak-width skeletonized mean diffusivity, an imaging marker for white-matter damage. Conversely, a higher free leptin index was linked to improved fractional anisotropy.

These results were further validated in a study of 89 cognitively healthy Hispanic participants from San Antonio, conducted by MarkVCID—a consortium of U.S. academic medical centers focused on identifying biomarkers for small vessel diseases of the brain that contribute to cognitive impairment and dementia (VCID).

The researchers concluded that higher leptin bioavailability is linked to better white-matter integrity in cognitively healthy middle-aged adults, reinforcing leptin’s neuroprotective role in reducing the risk of late-life dementia.

Reference

“Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age” by Sokratis Charisis, Meghan I. Short, Rebecca Bernal, Tiffany F. Kautz, Hector A. Treviño, Julia Mathews, Angel Gabriel Velarde Dediós, Jazmyn A. S. Muhammad, Alison M. Luckey, Asra Aslam, Jayandra J. Himali, Eric L. Shipp, Mohamad Habes, Alexa S. Beiser, Charles DeCarli, Nikolaos Scarmeas, Vasan S. Ramachandran, Sudha Seshadri, Pauline Maillard, and Claudia L. Satizabal, published 12 August 2024, Alzheimer’s & Dementia.
DOI: 10.1002/alz.13879.