An estimated 6.9 million Americans aged 65 and older are currently living with Alzheimer’s disease, according to the Alzheimer’s Association. This number is expected to increase to 13 million by 2050 unless medical breakthroughs are made to prevent or cure the disease.
Now, researchers have made significant advancements toward identifying the onset of Alzheimer’s in the brain 20 years before the earliest symptoms of dementia appear. They linked a specific type of body fat to the abnormal proteins in the brain that are hallmarks of Alzheimer’s disease.
Researchers emphasized that lifestyle changes aimed at reducing this fat could impact the development of Alzheimer’s disease.
Lead study author Mahsa Dolatshahi, M.D., M.P.H., post-doctoral research associate at Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri, said, “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.”
In the study, researchers explored the connection between lifestyle factors, such as obesity, body fat distribution, and metabolic aspects, and Alzheimer’s disease pathology. The study involved 80 cognitively normal midlife individuals (average age: 49.4 years, 62.5% female). Approximately 57.5% of participants were obese, with an average BMI of 32.31.
Participants underwent brain PET scans, body MRIs, metabolic assessments (glucose and insulin measurements), and lipid panels. MRI scans measured subcutaneous and visceral fat, liver fat fraction, and muscle mass.
The researchers specifically investigated how BMI, fat distribution (visceral and subcutaneous fat), liver fat, thigh fat and muscle, insulin resistance, and HDL cholesterol levels were linked to amyloid and tau deposition in Alzheimer’s disease.
The study used thigh muscle scans to measure muscle and fat volume and PET scans to assess Alzheimer’s disease pathology by tracking amyloid plaques and tau tangles in the brain. It showed that higher visceral fat levels were linked to increased amyloid accumulation, accounting for 77% of the impact of high BMI on amyloid buildup.
Other types of fat did not explain the obesity-related increase in Alzheimer’s pathology. Dr. Dolatshahi noted that the study is the first to demonstrate these findings in midlife participants, who are still decades away from developing Alzheimer ‘s-related dementia.
The study also found that higher insulin resistance and lower HDL cholesterol were associated with increased amyloid in the brain. The impact of visceral fat on amyloid pathology was partially reduced in individuals with higher HDL levels. The team emphasized that managing Alzheimer’s risk in obesity should involve addressing the metabolic and lipid-related issues that often accompany higher body fat.
Dr. Dolatshahi said, “Although previous studies have shown the role of high BMI in damaging the cells of the brain, no similar study has investigated the differential role of visceral and subcutaneous fat or metabolic profile, especially in terms of Alzheimer’s amyloid pathology as early as midlife.”
“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.”
Drs. Raji, Dolatshahi, and colleagues also present a study at RSNA 2024 that shows how obesity and visceral fat reduce blood flow in the brain.
In that study, the researchers performed brain and abdominal MRI on cognitively normal midlife individuals with a wide range of BMI and compared whole-brain and regional cerebral blood flow on brain MRI in individuals with high vs. low visceral and subcutaneous fat. The high visceral fat group showed lower whole-brain blood flow. No significant difference was observed in cerebral blood flow in the groups with high vs. low subcutaneous fat.
“This work will have a considerable impact on public health because nearly three out of four Americans are overweight or obese,” Dr. Raji said. “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.”
This study is being presented today at the annual meeting of the Radiological Society of North America (RSNA).