Hidden fat predicts Alzheimer's 20 years ahead of symptoms

Researchers have linked a specific type of body fat to the abnormal proteins in the brain that are hallmarks of Alzheimer's disease up to 20 years before the earliest symptoms of dementia appear, according to a study being presented today at the annual meeting of the Radiological Society of North America (RSNA). The researchers emphasized that lifestyle modifications targeted at reducing this fat could influence the development of Alzheimer's disease.

"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," said 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. An estimated 6.9 million Americans, aged 65 and older, are living with Alzheimer's disease, according to the Alzheimer's Association. The association estimates this number could grow to 13 million by 2050, barring the development of medical breakthroughs to prevent or cure the disease. 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. A total of 80 cognitively normal midlife individuals (average age: 49.4 years, female: 62.5%,) were included in the study. Approximately 57.5% of participants were obese, and the average body mass index (BMI) of the participants was 32.31. The participants underwent brain positron emission tomography (PET), body MRI and metabolic assessment (glucose and insulin measurements), as well as a lipid (cholesterol) panel. MRI scans of the abdomen were performed to measure the volume of the subcutaneous fat (the fat under skin) and visceral fat (deep hidden fat surrounding the 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," said Dr. Dolatshahi, a member of the Raji Lab at MIR's Neuroimaging Labs Research Center. 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. The findings revealed that higher levels of visceral fat were related to increased amyloid, accounting for 77% of the effect of high BMI on amyloid accumulation. 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," Dr. 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 study also showed that higher insulin resistance and lower HDL were associated with high amyloid in the brain. The effects of visceral fat on amyloid pathology were partially reduced in people with higher HDL. "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 senior study author Cyrus A. Raji, M.D., Ph.D., associate professor of radiology at MIR. 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, Dr. Dolatshahi pointed out. "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," Dr. Dolatshahi said. Drs. Raji, Dolatshahi and colleagues are also presenting 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." Other co-authors are Paul K. Commean, B.E.E., Mahshid Naghashzadeh, M.S., Sara Hosseinzadeh Kassani, Ph.D., Jake Weeks, B.S., Caitlyn Nguyen, B.S., Abby McBee-Kemper, B.S., Nancy Hantler, B.S., LaKisha Lloyd, M.Sc., Shaney Flores, M.S., Yifei Xu, M.S., Jingxia Liu, Ph.D., Claude B. Sirlin, M.D., Bettina Mittendorfer, Ph.D., Joseph E. Ippolito, M.D., Ph.D., John C. Morris, M.D., and Tammie L.S. Benzinger, M.D., Ph.D. This study was awarded the RSNA Trainee Research Prize.

Loss of smell and taste validated as COVID-19 symptoms in patients with high recovery rate

Loss of smell and taste has been anecdotally linked to COVID-19 infections. In a study published April 12, 2020 in the journal International Forum of Allergy & Rhinology, researchers at UC San Diego Health report the first empirical findings that strongly associate sensory loss with COVID-19, the respiratory disease caused by the novel coronavirus.

"Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms," said Carol Yan, MD, an otolaryngologist and head and neck surgeon at UC San Diego Health. "We know COVID-19 is an extremely contagious virus. This study supports the need to be aware of smell and taste loss as early signs of COVID-19."

Yan and colleagues surveyed 1,480 patients with flu-like symptoms and concerns regarding potential COVID-19 infection who underwent testing at UC San Diego Health from March 3 through March 29, 2020. Within that total, 102 patients tested positive for the virus and 1,378 tested negative. The study included responses from 59 COVID-19-positive patients and 203 COVID-19-negative patients.

Yan said the study demonstrated the high prevalence and unique presentation of certain sensory impairments in patients positive with COVID-19. Of those who reported loss of smell and taste, the loss was typically profound, not mild. But encouragingly, the rate of recovery of smell and taste was high and occurred usually within two to four weeks of infection.

"Our study not only showed that the high incidence of smell and taste is specific to COVID-19 infection, but we fortunately also found that for the majority of people sensory recovery was generally rapid," said Yan. "Among the Covid-19 patients with smell loss, more than 70 percent had reported improvement of smell at the time of survey and of those who hadn't reported improvement, many had only been diagnosed recently."

Sensory return typically matched the timing of disease recovery. Interestingly, the researchers found that persons who reported experiencing a sore throat more often tested negative for COVID-19.

In an effort to decrease risk of virus transmission, UC San Diego Health now includes loss of smell and taste as a screening requirement for visitors and staff, as well as a marker for testing patients who may be positive for the virus.

Other known symptoms of COVID-19 include fever, fatigue, cough and difficulty breathing. Respondents in Yan's study were most often persons with milder forms of COVID-19 infection who did not require hospitalization or intubation. The findings, she said, underline the importance of identifying early or subtle symptoms of COVID-19 infection in people who may be at risk of transmitting the disease as they recuperate within the community.

"It is our hope that with these findings other institutions will follow suit and not only list smell and taste loss as a symptom of COVID-19, but use it as a screening measure for the virus across the world," Yan said.

Co-authors include: Farhoud Faraji, Divya P. Prajapti, Christine E. Boone and Adam S. DeConde, all at UC San Diego.

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Story Source:

Materials provided by University of California - San Diego. Original written by Jeanna Vazquez. Note: Content may be edited for style and length.

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Journal Reference:

1. Carol H. Yan, Farhoud Faraji, Divya P. Prajapati, Christine E. Boone, Adam S DeConde. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. International Forum of Allergy & Rhinology, 2020; DOI: 10.1002/alr.22579