Research: Midlife Obesity May Be Linked to Alzheimer’s Disease

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Midlife obesity is associated with thinner cerebral cortices in regions of the brain related to Alzheimer’s disease. Cerebral cortices make up the outermost layer of the brain and consist of mostly grey matter.

Adiposity, another term for obesity, was also linked to thinner cortices in other parts of the brain.

A major public health concern

“Midlife obesity is a major public health problem and can have an impact on the risk of neurodegenerative disorders, such as Alzheimer’s disease,” said study co-author Dr. Ralph L. Sacco, professor and Olemberg Chair of Neurology. The study titled “Measures of Adiposity and Alzheimer’s Disease-Related MRI Markers: The Northern Manhattan Study,” was published recently in the Journal of Alzheimer’s Disease.

The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the Evelyn F. McKnight Brain Institute. It adds a new perspective to the research team’s high-profile findings regarding obesity and global brain atrophy published in the July 2019 issue of the journal Neurology.

The Northern Manhattan Study, a collaboration between the Miller School and Columbia University, focuses on a clinically stroke-free cohort of mostly Hispanic participants. “It continues to shed light on some important midlife modifiable risk factors for cognitive decline,” said Dr. Sacco, who is also executive director of the Evelyn F. McKnight Brain Institute, chief of neurology at Jackson Memorial Hospital, director of UM’s Clinical and Translational Science Institute, and senior associate dean for clinical and translational science at the Miller School.

“Our new study shows a strong link between midlife obesity and changes in brain structure,” said senior author Dr. Tatjana Rundek, professor of neurology, Evelyn F. McKnight Chair for Learning and Memory in Aging, and scientific director of the Evelyn F. McKnight Brain Institute. “These results are particularly relevant for diverse populations with a large proportion of minorities such as in the Northern Manhattan Study cohort, where midlife weight control is especially important to reduce long-term health risks.”

The Miller School researchers examined the records of 947 Northern Manhattan study participants. Women made up 63 percent, 66 percent were Hispanic, and 25 percent were obese. From those records, they took the participants’ body mass index, waist-hip ratio, waist circumference, and concentrations of the adiponectin hormone, and used Freesurfer brain imaging software to map cortical thickness.

First study author Dr. Michelle R. Caunca, in the Miller School’s Medical Scientist Training Program, said that study participants with greater body mass index and waist circumference had thinner average cortex layers in regions of their brains.  Cortical thickness has been used as a research tool in studying Alzheimer’s disease diagnoses in older adults, she says. But it has not been validated for clinical purposes.

“Our study suggests that weight status, especially before older age, is related to less gray matter later in life,” said Dr. Caunca.

“It is possible that the chronic inflammatory state of obesity or an increased resistance to insulin could affect the cortex, but more research needs to be done to uncover the mechanisms. We hope to extend our work on whether changes in weight can impact brain health later in life.”

Other Miller School co-authors were Dr. Marialaura Simonetto, and Dr. Noam Alperin, along with Dr. Clinton Wright, associate director of NINDS and a former Miller School professor, and Dr. Mitchell S.V. Elkind, professor of neurology at Columbia University and 2019-20 president-elect of the American Heart Association.


Written by Richard Westlund for Inventum.