Leptin Variation May Affect Brain Health and Development of Dementia

New research links obesity to dementia.

High levels of leptin, a hormone that helps maintain a normal body weight, are associated with poor brain function in middle-aged adults, according to a study by The University of Texas Health Science Center in San Antonio (UT Health San Antonio). ).

Claudia Satizabal said: “The findings support the well-known differential role of leptin in the risk of late-onset dementia by affecting its deficiency and structural changes in white matter, which is the first functional event of the disease. mental retardation due to Alzheimer’s disease or neurological dementia,” said Claudia Satizabal. , PhD, assistant professor at the Glenn Biggs Center for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio.

Satizabal is the lead author of a study called, “Leptin bioavailability and markers of brain atrophy and vascular injury in middle age,” published Aug. 12 in Alzheimer’s & Dementia: Journal of the Alzheimer’s Association. Other authors include the Biggs Institute, as well as Tufts Medical Center in Boston; 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 leading cause of dementia, affecting the lives of millions of people worldwide, according to study data. A growing body of evidence suggests that midlife obesity is an important risk factor for developing the disease.

This has led to a growing interest in unraveling the mechanisms linking obesity and Alzheimer’s, which may extend to vascular, genetic and metabolic pathways. And the study of adipose tissue has led to important insights.

Once thought of as an energy store, adipose tissue is now considered part of the endocrine system, producing a group of bioactive peptides known as adipokines, or signaling molecules. cells that play energy or metabolic functions in the body. , inflammation and obesity.

Leptin is an adipokine responsible for the central control of food intake and energy homeostasis, and is involved in various neurophysiological functions, including brain development, neurogenesis and neuroprotection.

Because of these effects, it has been considered a logical step in the pathway leading from obesity to Alzheimer’s disease. It is supported by studies that link high leptin levels to lower risk of Alzheimer’s disease and cognitive impairment, as well as improved brain symptoms in adults, the study notes.

However, studies conducted in young people have not seen a relationship between leptin and early signs of brain damage before the risk of late-onset dementia. Researchers in a new study at UT Health San Antonio aim to gain more information about leptin’s potential relationship with neurodegenerative and cerebrovascular burden.

Specifically, they investigated the relationships of leptin markers with cognitive function and brain magnetic resonance imaging (MRI) measures and vascular risk in healthy adults. well middle aged.

They performed neurological examinations of 2,262 mentally healthy participants from the Framingham Heart Study, a long-term cardiovascular study of the population of Framingham, Massachusetts, that spanned three generations and is now a project of the National Heart, Lung and Blood Institute, in collaboration with Boston. University.

The scientists measured the concentrations of leptin, its soluble receptor and their ratio, known as the free leptin index, indicating leptin bioavailability, using immunosorbent assays related to enzyme. Psychological and MRI measures were obtained using standard protocols.

The results found a high correlation of soluble leptin receptor with low anisotropy, a biomarker of brain white-matter integrity, and peak-width skeletonized mean diffusivity, an imaging marker for white matter injury. Similarly, a higher free leptin index was associated with a higher degree of anisotropy.

These results were replicated in a study that included 89 participants from San Antonio who were mentally healthy, by MarkVCID, an association of US academic medical centers whose purpose is to identify and validating biomarkers for small vessel diseases of the brain that result in neurological deficits. disability and dementia (VCID).

Taken together, the researchers concluded that higher leptin bioavailability is associated with better white matter integrity in healthy middle-aged adults, supporting leptin’s role in “dementia” at risk in later life.

UT Health San Antonio is the largest academic research institution in South Texas, with an annual research portfolio of $413 million.