A team of researchers in the U.S. and Israel used magnetic resonance imaging (MRI) to measure the amounts of fat in subjects’ liver, abdomen, and pancreas. Higher pancreatic fat correlated to lower cognition and smaller volumes of brain regions linked to Alzheimer’s—primarily in men. These findings were published this week in the journal Obesity.

Studying people at high risk of Alzheimer’s in middle age is important because the underlying signs of the disease, the most common form of dementia, begin developing 20 to 30 years before symptoms appear, says Michal Schnaider Beeri, Ph.D., director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at the Rutgers Brain Health Institute, who led the study.

“We want to know who are those who are in a bad trajectory, in order to do everything possible to prevent it,” she tells Fortune. “And, alternatively, who are those that despite their very high risk [are] not in a bad trajectory, and then to learn from their resilience.”

Previous research has shown a link between obesity and brain health—lower cognitive functioning and higher dementia risk—traditionally using body mass index (BMI). But Beeri’s team notes that BMI, a calculation of body fat based on your height and weight, doesn’t account for body fat distribution.

“I believe we are the first to show that fat on the pancreas is related to poorer cognitive function and a smaller cortical brain volume in people who are in midlife,” Beeri says. “The associations that we found between fat and cognition and brain volumes were not found for BMI.”

Beeri isn’t surprised the pancreas is at the center of the study results, largely because of its relationship to Type 2 diabetes. The disease, which results when the pancreas doesn’t make enough of the glucose-regulating hormone insulin and/or your body doesn’t use it properly, is a well-documented risk factor for dementia.

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Who is at high risk of Alzheimer’s?

Age is the greatest risk factor for the neurodegenerative disease, according to the Alzheimer’s Association, as most people with the condition are 65 or older. After 65, your risk of developing the disease doubles every five years. Compared to older white people, older Black people are twice as likely to have Alzheimer’s, while older Latinos are 1 ½ times as likely.

Serious medical conditions including stroke, heart disease, diabetes, high blood pressure, and high cholesterol may increase your risk. A link also exists between traumatic brain injury and dementia.

People who have a parent or sibling with Alzheimer’s are more likely to develop the disease, and that risk increases if more than one family member is ill, according to the Alzheimer’s Association. This study drew 204 participants from the Israel Registry for Alzheimer’s Prevention (IRAP) study whose parents had been diagnosed with Alzheimer’s. They were cognitively asymptomatic, between the ages of 40 and 65 with an average age of 59, and 60% female.

IRAP participants already had completed neuropsychological tests in these categories:

• Episodic memory: recollection of past experiences
• Executive function: mental processes including self-control and creative thinking
• Working memory: readily accessible information that can be used for tasks such as problem solving
• Language: includes verbal IQ
• Global cognition: overall cognitive function

How is abdominal fat linked to brain health?

All participants in this latest study underwent imaging of their abdominal organs. Of those, 142 also had a structural volumetric brain MRI. In addition to total gray matter, these scans measured specific brain regions related to Alzheimer’s:

• Hippocampus: learning and memory
• Inferior frontal gyrus (IFG): speech production
• Middle frontal gyrus (MFG): literacy and numeracy
• Superior frontal gyrus (SFG): working memory, spatial processing, impulse control

Higher pancreatic fat percentage was linked to smaller IFG volume, lower global cognition, lower executive function, and lower episodic memory function, most notably in men. In women, higher pancreatic fat was linked to smaller hippocampal volume; about two-thirds of U.S. Alzheimer’s patients are women, and the hippocampus is one of the first regions affected by the disease.

“What seems to happen is that when fat is sitting on a certain organ, the fat itself or the organ has certain secreted factors that are not secreted in a normal way,” Beeri explains. “Some of those cross the blood-brain barrier and then they do the damage or, alternatively, they’re protective.”

Researchers didn’t find an association between liver fat percentage and cognitive functioning or regional brain volumes for either sex. In both men and women, higher liver fat was associated with smaller total gray matter volume, but this link lost statistical significance when the data were adjusted for participants’ cardiovascular risk factors.

Beeri and her team measured two types of belly fat: subcutaneous, located just under the skin, and visceral, which is buried in the abdominal cavity. In men, higher subcutaneous fat was tied to smaller MFG volume. Higher visceral fat was tied to larger SFG and MFG volumes, but also only in men. Neither type of belly fat was associated with cognitive functioning in either sex.

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Why is abdominal fat more strongly tied to brain health in men?

“We don’t really know why [the] strongest effect is among men,” Beeri tells Fortune, noting this puzzle provides the natural next step in her team’s research. “We are hoping to disentangle some differences between sexes in that regard.”

One possible explanation is that men and women not only store body fat differently, but also do so in ways that change with age, says Dr. Nisha Patel, an obesity medicine physician in San Francisco.

“Men [have] more visceral adiposity from the get-go, and then women catch up when they transition through menopause,” Patel tells Fortune. “What really happens because of the low estrogen is a repartitioning of fat.”

Before women hit menopause, however, estrogen may offer neuroprotection, Patel says: “We do know that there’s estrogen receptors in the brain.”

Future studies on the connection between abdominal fat and brain health should entail a larger sample size more representative of the middle-aged adult population, including people without a family history of Alzheimer’s, Beeri and her colleagues noted. Factors such as participants’ dietary and exercise habits will be key.

For now, Beeri says the most important thing for people to remember is that being healthy in old age is a lifelong effort.

“There is good reason to believe that fat will affect your brain deleteriously,” she says. “Everything that you can do, at least on a lifestyle level, to protect yourself from that, do it.”

Patel calls obesity treatment “a lifelong marathon” and cautions against “gimmicky,” quick-fix diets and workouts that claim to blast belly fat. You’re better off managing your weight long term by engaging in regular aerobics and strength training, eating a balanced diet, getting adequate sleep, and limiting stress, she says.

“There’s no way to really effectively target belly fat except to encourage total-body weight loss,” Patel says.

For more on Alzheimer’s disease and dementia: 

• Viagra may help reduce Alzheimer’s risk, according to a new study. An expert explains the surprising connection
• TV personality Wendy Williams receives identical diagnoses to Bruce Willis—frontotemporal dementia and primary progressive aphasia
• Taking a vitamin D supplement may lower your risk for dementia. Here are the groups who may benefit most
• Will you develop dementia? These 11 factors are strong predictors in middle age, scientists say