Scientists Identify Hidden Midlife Risk for Developing Alzheimer's Disease

The development of Alzheimer's may be linked to having more of a gut in middle age, scientists have discovered.

Higher levels of visceral fat—surrounding the internal organs, hidden deep within the abdomen—are linked with changes in the brain, sometimes up to 15 years before any memory-loss symptoms of Alzheimer's begin. This is according to new research to be presented at the annual meeting of the Radiological Society of North America (RSNA) between November 26 and 29.

"This study highlights a key mechanism by which hidden fat can increase the risk of Alzheimer's disease," co-author Cyrus A. Raji said in a statement. He is an associate professor of radiology and neurology and director of neuromagnetic resonance imaging at Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri. "It shows that such brain changes occur as early as age 50, on average—up to 15 years before the earliest memory-loss symptoms of Alzheimer's occur."

Alzheimer's disease affects the functioning of the brain, leading to the development of dementia. The disease is associated with the build-up of proteins called amyloid and tau. These cluster into structures called plaques and tangles that damage and clog up the functioning of the brain. Around 5.8 million adults live with Alzheimer's disease and other dementias in the U.S., according to the U.S. Centers for Disease Control and Prevention (CDC), with the number being predicted to rise to 13 million by 2050.

"Amyloid and tau are abnormally folded proteins outside and inside brain cells that kill neurons over time, especially parts of the brain responsible for memory and cognition. This results in the memory loss symptoms we know of as Alzheimer's disease," Raji told Newsweek.

The researchers investigated the link between amyloid and tau uptake on positron emission tomography (PET) scans, as well as brain MRIs measuring the thickness of brain areas affected by Alzheimer's, with factors including body mass index (BMI), obesity, insulin resistance, subcutaneous fat (under the skin), and visceral fat levels in 54 healthy participants between the ages of 40 and 60. These participants had an average BMI of 32.

A healthy weight is considered to be between 18.5 to 24.9, according to the CDC, with 25 and above being classified as overweight and 30 or over being obese. The visceral fat levels were measured using abdominal MRI. Only 32 of the participants underwent PET scans.

"Even though there have been other studies linking BMI with brain atrophy or even a higher dementia risk, no prior study has linked a specific type of fat to the actual Alzheimer's disease protein in cognitively normal people," Mahsa Dolatshahi, a postdoctoral research fellow with MIR, and study co-author, said in a statement. "Similar studies have not investigated the differential role of visceral and subcutaneous fat, especially in terms of Alzheimer's amyloid pathology, as early as midlife."

The scientists found that higher amyloid uptake in the precuneus cortex—a brain region affected early by amyloid pathology in Alzheimer's disease—was linked to a higher ratio of visceral to subcutaneous fat, with this connection being stronger in men than in women. They also discovered that higher levels of visceral fat were linked to increased brain inflammation.

"Higher visceral fat can promote insulin resistance that can contribute to competitive inhibition of enzymatic breakdown of amyloid in the brain. Also, higher visceral fat promotes neuroinflammation that can interact with Alzheimer's pathology to worsen neuronal loss," Raji said.

The authors hope these discoveries could be used to diagnose Alzheimer's even earlier, hopefully allowing for better intervention treatments.

"A 15-year window between the detection of Alzheimer's pathology and development of symptoms allows for the application of brain health-based prevention strategies and potentially new drugs that can remove the pathological burden of the disease before symptoms arise," Raji said.

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Update 11/21/23, 11:26 a.m. ET: This article was updated with comment from Cyrus A. Raji