New research links obesity more closely to dementia.
Higher levels of leptin, a hormone that helps maintain normal body weight, are associated with better brain white matter signaling in middle-aged adults, according to a study from the University of Texas Health Science Center at San Antonio (UT Health San Antonio).
The findings support the known role of leptin variations in the risk of dementia later in life by relating its deficiency to changes in white matter structure, which is an early event in the process of cognitive impairment due to Alzheimer’s disease or vascular dementia.”
Claudia Satizabal, PhD, Associate Professor, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio
Satizabal is lead author of the study entitled “Leptin bioavailability and markers of brain atrophy and vascular damage in the middle age”, published on August 12 in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association. Other authors are also affiliated with the Biggs Institute and 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 leading cause of dementia and impacts the lives of millions of people around the world, the study said. There is increasing evidence that obesity in middle age is a major contributor to the risk of developing the disease.
This has led to growing interest in disentangling the mechanisms linking obesity to Alzheimer’s disease, which may extend through vascular, genetic, and metabolic pathways. And the study of adipose or adipose tissue has led to important insights.
Once seen as a passive reservoir for energy storage, adipose tissue is now considered part of the endocrine system, secreting a group of bioactive peptides known as adipokines, or cell signaling molecules that play a functional role in energy or metabolic status of the body. , inflammation and obesity.
Leptin is an adipokine responsible for the central control of food intake and energy homeostasis, and is involved in a variety of neurophysiological functions including brain development, neurogenesis and neuroprotection.
Because of these effects, it is considered a plausible mechanism in the pathway leading from obesity to Alzheimer’s disease. It is supported by findings linking higher leptin levels to a lower risk of Alzheimer’s disease and mild cognitive impairment, as well as better structural brain indicators in older adults, the study notes.
Yet studies in younger individuals have found no associations between leptin and early indicators of brain damage prior to dementia risk later in life. Researchers in the new study from UT Health San Antonio wanted to better understand leptin’s potential relationships with neurodegenerative and cerebrovascular burden.
Specifically, they examined the associations of leptin markers with cognitive functions and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.
They conducted neuropsychological evaluations of 2,262 cognitively healthy participants from the Framingham Heart Study, a long-term cardiovascular cohort study of Framingham, Massachusetts, residents that spans 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, the soluble leptin receptor and their ratio, known as the free leptin index, which indicates the bioavailability of leptin, using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols.
The results found a higher association of the soluble leptin receptor with lower fractional anisotropy, a biomarker of brain white matter integrity, and skeletonized mean diffusivity with peak width, an imaging marker of white matter injury. Accordingly, a higher free leptin index was associated with higher fractional anisotropy.
These results were replicated in a study involving 89 cognitively healthy Hispanic participants from San Antonio by MarkVCID, a consortium of U.S. academic medical centers whose mission is to identify and validate small-brain biomarkers that make vascular contributions to cognitive disorders. disability and dementia (VCID).
Taken together, the researchers concluded that higher leptin bioavailability was associated with better white matter integrity in healthy middle-aged adults, supporting leptin’s putative neuroprotective role in dementia risk later in life.
UT Health San Antonio is the largest academic research institution in South Texas, with an annual research portfolio of $413 million.
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Magazine reference:
Charisis, S., et al. (2024). Leptin bioavailability and markers of brain atrophy and vascular injury in middle age. Alzheimer’s and dementia. doi.org/10.1002/alz.13879.