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Higher levels of visceral fat were correlated with more amyloid plaque in the brains of cognitively normal individuals, according to a study that hints as to why individuals with obesity are more prone to dementia.

Amyloid levels were higher among individuals with obesity compared to those without obesity (P=0.008), and were significantly associated with visceral adipose tissue (P<0.0001), found researchers led by Mahsa Dolatshahi, MD, of Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis.

Higher levels of visceral fat were related to increased amyloid, accounting for 77% of the effect of high body mass index (BMI) on amyloid accumulation, Dolatshahi reported at the annual meeting of the Radiological Society of North America. Other types of fat did not explain obesity-related increased Alzheimer's pathology.

"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 said. "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."

The researchers also suggested that higher insulin resistance and lower HDL cholesterol were associated with high amyloid in the brain. The study showed effects of visceral fat on amyloid pathology were partially reduced in people with higher HDL, Dolatshahi said.

"Higher levels of HDL -- good cholesterol -- appears to ameliorate the effects of fat on Alzheimer's-associated pathologies such as amyloid in the brain," said Dolatshahi.

She suggested that modifying lifestyle to reduce fat and increase HDL levels could have a beneficial effect in preventing or delaying progression to Alzheimer's disease.

Study co-author Cyrus Raji, MD, PhD, also of Mallinckrodt, suggested that treatment with new weight-loss drugs "may have brain health benefits in midlife that may prevent Alzheimer's disease later in life."

"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," said Raji.

In commenting on the study, Max Wintermark, MD, chair of neuroradiology at the University of Texas MD Anderson Cancer Center in Houston, told MedPage Today, "Physicians should, of course, advise their patients on the very many benefits of weight loss, which are well known. Regarding this study, in particular, it raises some interesting points, but the results need to be considered with caution, given the small number of patients studied."

"Further investigations are needed to confirm the association found by the authors and, most importantly, to determine whether weight loss can reverse some of these changes," Wintermark added.

For the study, the researchers focused on the link between modifiable lifestyle-related factors -- such as obesity, body-fat distribution, and metabolic aspects -- and Alzheimer's disease pathology.

They recruited 80 cognitively normal individuals in midlife (mean age 49.4). Men made up 62.5% of the sample. The cohort's mean BMI was 32.3, and 57.5% of the group was diagnosed as being obese. The participants underwent PET, body MRI, and metabolic assessment as well as lipid panel blood testing. MRI scans of the abdomen were performed to measure the volume of the subcutaneous fat and visceral fat.

Thigh muscle scans were used to measure volume of muscle and fat. Alzheimer's disease pathology was measured using PET scans with tracers that bind to amyloid plaques and tau tangles that accumulate in the brains of people with Alzheimer's disease.

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