Hidden body fat predicts Alzheimer’s 20 years before symptoms

Researchers have uncovered a connection between a specific type of body fat and the abnormal brain proteins associated with Alzheimer’s disease, detectable up to 20 years before the first signs of dementia. 

This discovery, presented at the Radiological Society of North America (RSNA) annual meeting, highlights the potential for lifestyle interventions targeting this fat to influence Alzheimer’s development.

Early detection of Alzheimer’s 

Study lead author Mahsa Dolatshahi is a postdoctoral research associate at the Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri.

“This crucial result was discovered because we investigated Alzheimer’s disease pathology as early as midlife – in the 40s and 50s – when the disease pathology is at its earliest stages, and potential modifications like weight loss and reducing visceral fat are more effective as a means of preventing or delaying the onset of the disease,” explained Dolatshahi. 

With 6.9 million Americans over 65 currently living with Alzheimer’s – a figure projected to double by 2050 without medical breakthroughs – early interventions could significantly alter the trajectory of the disease.

Lifestyle factors and Alzheimer’s disease 

The study examined how obesity, fat distribution, and metabolic factors contribute to Alzheimer’s pathology. It involved 80 cognitively normal middle-aged participants, with an average age of 49.4 years. 

Among them, 57.5% were obese, with an average body mass index (BMI) of 32.31. Participants underwent brain PET scans, body MRI scans, metabolic assessments, and cholesterol analysis. MRI scans of the abdomen measured subcutaneous fat (fat beneath the skin) and visceral fat (fat surrounding internal organs).

“We investigated the association of BMI, visceral fat, subcutaneous fat, liver fat fraction, thigh fat and muscle, as well as insulin resistance and HDL (good cholesterol), with amyloid and tau deposition in Alzheimer’s disease,” Dolatshahi said.

Visceral fat and brain protein accumulation

The team analyzed thigh muscle scans to assess fat and muscle volumes, while PET scans measured amyloid plaques and tau tangles – abnormal proteins linked to Alzheimer’s.

Their results showed that higher levels of visceral fat were strongly associated with amyloid accumulation, explaining 77% of the relationship between high BMI and amyloid buildup. Other fat types, such as subcutaneous fat, did not account for this link.

“Our study showed that higher visceral fat was associated with higher PET levels of the two hallmark pathologic proteins of Alzheimer’s disease – amyloid and tau,” Dolatshahi noted. 

“To our knowledge, our study is the only one to demonstrate these findings at midlife where our participants are decades out from developing the earliest symptoms of the dementia that results from Alzheimer’s disease.”

Metabolic health and Alzheimer’s risk

The researchers found that increased insulin resistance and reduced HDL (good cholesterol) levels were linked to higher amyloid accumulation. Interestingly, higher HDL levels partially mitigated the impact of visceral fat on Alzheimer’s pathology.

“A key implication of our work is that managing Alzheimer’s risk in obesity will need to involve targeting the related metabolic and lipid issues that often arise with higher body fat,” explained senior study author Cyrus A. Raji, an associate professor of radiology at MIR.

A deeper look at body fat distribution

While prior studies have linked high BMI to brain health, this research is unique in distinguishing the effects of visceral fat from other types of body fat.

“This study goes beyond using BMI to characterize body fat more accurately with MRI and, in so doing, reveals key insights about why obesity can increase risk for Alzheimer’s disease,” Dolatshahi said.

Obesity and brain blood flow

In a related study also presented at RSNA 2024, the team explored how obesity and visceral fat affect brain blood flow. Using MRI scans, researchers compared cerebral blood flow in individuals with high versus low visceral and subcutaneous fat. Those with high visceral fat exhibited reduced blood flow throughout the brain, while subcutaneous fat showed no significant impact.

“This work will have a considerable impact on public health because nearly three out of four Americans are overweight or obese,” said Raji.

‘Knowing that visceral obesity negatively affects the brain opens up the possibility that treatment with lifestyle modifications or appropriate weight-loss drugs could improve cerebral blood flow and potentially lower the burden of and reduce the risk for Alzheimer’s disease.”

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