June 7, 2024 – If you discover out, you'll almost definitely Alzheimer Illness in some unspecified time in the future in the longer term, what would you do?
What could you do?
This is an issue that many researchers and doctors are grappling with after a gaggle of Alzheimer's researchers recently suggested that genetics alone could discover upfront as much as 20% of people that will ultimately be diagnosed with the devastating type of Alzheimer's disease. dementia.
“The real question – and the risk – is: If you identify people at this stage, what are you going to do, because we don't yet know exactly the spectrum of disease progression over time,” said geriatric psychiatrist Marc E. Agronin, MD, an Alzheimer's expert and chief medical officer at the Frank C. and Lynn Scaduto Mind Institute at Miami Jewish Health in Florida.
The proposal raises the difficult question of whether people should be tested for the specific APOE4 gene variant that has long been linked to Alzheimer's disease. Carrying two copies of APOE4 only occurs in about 2 in 100 people, so is unusual. But the new studypublished in May within the magazine Natural medicinefound that 95% of carriers developed signs of Alzheimer's of their brain or bodily fluids. And these signs appeared, on average, nearly 20 years before the Alzheimer's diagnosis.
But not everyone with two copies of APOE4 had other clinical symptoms that typically trigger an Alzheimer's diagnosis, akin to severe memory, mood and pondering problems. Because APOE4 testing will not be typically really useful as a part of preventive care, carriers are sometimes unaware they've the variant, even when they struggle to take proactive measures, akin to weight-reduction plan and lifestyle changes, to cut back their risk of Alzheimer's.
Biomarkers are abundant in APOE4 markers
The apolipoprotein E gene (APOE for brief) is related to the chance of Alzheimer's disease since it is involved within the body's own means of Transport cholesterol and other fats within the bloodstream. People can have different versions of the APOE gene, receiving input from each parent. Up to twenty% of individuals have one copy of APOE4 and only 2% of individuals have two copies. People with two copies of APOE4 are called “APOE4 homozygotes” in scientific terminology.
The Natural medicine The study checked out data from 3,300 donated brains and the health records of about 10,000 people to learn how the presence of two copies of APOE4 could also be linked to telltale signs of Alzheimer's within the brain and differences in disease and symptom progression depending on an individual's age. In total, the study included the brains of 273 individuals who had two copies of APOE4 and the health records of 519 individuals who also had two copies.
The researchers found that the brains of people that were homozygous for APOE4 began to point out signs of Alzheimer's changes at a median age of about 55. Symptoms began at a median age of 65, mild problems with pondering ability were diagnosed at about 72, after which dementia was diagnosed at about 74.
Overall, the researchers found a consistent and progressive story told by biomarkers and brain changes revealed by brain imaging and laboratory tests of body fluids. All disease progression markers typically appeared 7 to 10 years earlier in APOE4 homozygotes than in individuals with other APOE variants. The consistency in the information led the researchers to imagine that carrying two copies of APOE4 is “deterministic” for developing AD, not only predictive. If this assumption becomes widely accepted, it could make Alzheimer's one of the common inherited diseases on this planet.
“For me, the really important thing here is the promise that we might be able to treat people before symptoms appear, especially those who already have the disease in their brain,” said Dr. Reisa Sperling, a neurologist and Alzheimer's researcher at Massachusetts General Hospital in Boston. Sperling was not involved within the study but spoke at a press conference held by Natural medicine.
Genetic test results aren't a guarantee
Experts caution that the brand new study's findings have significant limitations, which must be of concern to individuals who wish to study APOE4 and get tested, as that is widely available on the industrial market.
The data for the study included primarily only whites of European descent and got here entirely from databases focused on Alzheimer's research.
“This is an exciting time in Alzheimer’s research. Scientists are regularly developing and investigating exciting new ideas. But at the moment, the Natural medicine “The study is simply a provocative idea that needs to be reproduced and confirmed, especially in study populations that more accurately reflect the diversity of people with Alzheimer's disease,” said Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer's Association.
Erin Coffman, MS, a clinical genetic counselor at the University of Texas Southwestern Medical Genetics Clinic in Dallas, agreed that the study's limitations are important. She doesn't expect the study to change the way she counsels patients. But she wouldn't be surprised if more people asked her about APOE testing.
“I really think this might spark interest in some people to meet with a genetic counselor and have an informed conversation about risk,” Coffman said, noting that this has also happened in conjunction with other high-profile news events, such as when celebrities are diagnosed with conditions that have a genetic link.
The American College of Medical Genetics and Genomics does not recommend predictive APOE testing, and she said it's rare that people decide to do it after talking to her. Most of her conversations about APOE4 test results are with people who schedule an appointment with her because they already have results on hand.
“A lot of people are just curious because they're looking for information, and many of those people have done direct-to-consumer testing and then may come to me to discuss their test results,” Coffman said.
She may refer the patient to a neurologist if there are concerns or simply talk to them about ways to reduce the overall risk of Alzheimer's disease.
“There's no guarantee that this will happen to them in their lifetime because we don't really know how long we're going to live,” Coffman said. “The counseling here is all about making sure people know the risk, but also that they have hope and know they can limit other risk factors.”
Agronin emphasized the importance of APOE4 testing being performed in a supportive context.
“My concern is that the results may be misinterpreted or there may be overreactions if the tests are done outside of genetic counseling or in collaboration with Alzheimer's experts without the necessary support,” he said. “Because the study clearly indicates that the development of Alzheimer's in people who are homozygous for APOE4 really does seem inevitable. In the past, we have tended to just talk about the higher risk and leave it at that.”
Susan D. Klugman, MD, president of the American College of Medical Genetics and Genomics, said the organization will look more closely at how the new study affects Recommendations for APOE testing.
“The findings from this article are fascinating and warrant further evaluation by national societies, including our own,” she said, adding that any consideration of updating a guideline would only come after a comprehensive review and not on the basis of a single study.
“Large-scale APOE genotyping and publication of results can be problematic and raise many ethical, legal and financial concerns,” warned Klugman.
The outliers: some never developed symptoms
The study in Natural medicine reported that not everyone who had two copies of APOE4 had the very same disease course. These outliers are areas that experts say raise essential questions for future research.
“It's important to know that some people with two copies of APOE4 live to old age and still don't get dementia,” Snyder said. “It's not predetermined or 'definite' that they will develop dementia due to Alzheimer's disease, even if they have the brain changes characteristic of the disease.”
It is significant to debate these discrepancies in study results during genetic counseling, said Coffman.
“This study also showed that the age at which the disease occurs varies greatly. It can be around 40 years, but also up to 81 or 82 years, and not everyone experiences any symptoms at all,” she explained.
If a middle-aged person got here to the clinic and asked for a genetic test but had no symptoms, he wouldn't refuse to provide them an APOE test, Agronin said.
“That's changing, and this study really takes us in that direction: Someone comes to us, they're in their 40s or 50s, and they want to know their genetics. They may have no symptoms at all, but let's say they're homozygous for APOE4,” he said. “So we know from the study that people in their mid-50s and older are likely to have Alzheimer's in their brain, and by age 65, three-quarters of them already have a positive PET scan, so they really are in a different category.”
Since this case is genetic, the news may not come as an entire surprise.
“Many of the people who come to us and have a strong family history are already prepared and eager to take action,” says Agronin, whose clinic also offers an Alzheimer's prevention program. The program focuses on a brain-healthy lifestyle and offers coaching to vary or reduce risk aspects.
“I've changed my language and my approach over the last decade,” Agronin said. “I never talk about someone who has a disease. I talk about people who live with neurocognitive changes, because that's exactly what they do.”