Alzheimer’s disease could be detected up to 20 years before dementia symptoms start to show following a major breakthrough.
Researchers have linked a specific type of body fat that surrounds vital organs in middle age to abnormal proteins in the brain that are hallmarks of the most common cause of dementia as early as two decades before the earliest symptoms appear.
The American team emphasised that lifestyle modifications targeted at reducing fat could influence the development of Alzheimer’s.
Study lead author Doctor Mahsa Dolatshahi 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.”
Up to one million people are believed to be living with dementia in the UK, with numbers forecast to rise, while an estimated 6.9 million Americans have Alzheimer’s.
For the new study, researchers focused on the link between modifiable lifestyle-related factors – such as obesity, body fat distribution and metabolic aspects – and Alzheimer’s disease pathology.
The study included 80 cognitively normal midlife individuals, with an average age of 49.4.
Just over of the participants (57.5%) were obese, and their average body mass index (BMI) was 32.31.
All the participants underwent brain positron emission tomography (PET), MRI plus glucose and insulin measurements, as well as a cholesterol panel.
MRI scans of the abdomen were performed to measure the volume of the subcutaneous fat—the fat under the skin—and visceral fat, the deep, hidden fat surrounding the organs.
Dr Dolatshahi of the Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri, said: “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.”
She said thigh muscle scans were used to measure muscle and fat volume.
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.
The findings, presented at the annual meeting of the Radiological Society of North America (RSNA) in Chicago, revealed that higher visceral fat levels were related to increased amyloid, accounting for 77% of the effect of high BMI on amyloid accumulation.
However, other types of fat did not explain obesity-related increased Alzheimer’s pathology.
Dr Dolatshahi said: “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.”
She added: “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 study also showed that higher insulin resistance and lower HDL were associated with high amyloid in the brain.
The findings show that the effects of visceral fat on amyloid pathology were partially reduced in people with higher HDL.
Study senior author Professor Cyrus Raji said: “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.”
Although previous studies have shown the role of high BMI in damaging the cells of the brain, Dr Dolatshahi pointed out that no similar research 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.
She added: “This study goes beyond using BMI to characterise body fat more accurately with MRI and, in so doing, reveals key insights about why obesity can increase risk for Alzheimer’s disease.”
The team are also due to present the findings of a study that shows how obesity and visceral fat reduce blood flow in the brain.
In that study, the researchers performed brain and abdominal MRIs on cognitively normal middle-aged men and women with a wide range of BMI and compared whole-brain and regional cerebral blood flow on brain MRI in people with high and low visceral and subcutaneous fat.
The high visceral fat group showed lower whole-brain blood flow.
However, cerebral blood flow was not significantly different in the groups with high compared to low subcutaneous fat.
Prof Raji said: “This work will have a considerable impact on public health because nearly three out of four Americans are overweight or obese.”
He added: “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.”