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With More Accurate Alzheimer’s Testing Coming, Would You Want to Know?

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Would you want to be able to see your future? Questions like that are usually the stuff of movies and fantasy stories where the hero or heroine is given the chance to glimpse the time to come. To know or not to know what lies out there in the years ahead? It’s a provocative question.

Now, thanks to scientific advances in testing, that question is slowly becoming less theoretical and more practical, at least as it applies to the disease many of us fear the most: Alzheimer’s disease. Today, accurate testing to see whether or not a patient is likely to suffer from Alzheimer’s disease in the future is still a dream of laboratory researchers. But tomorrow, or soon thereafter, tests might become available that are relatively cheap, readily available, and reasonably accurate. Then what?

The question is, would you take a test to tell you how likely you are to develop Alzheimer’s disease? Recently we discovered this article, reprinted from The Telegraph, on the GetPocket website. David Cox, reporter for The Telegraph, talked to several Alzheimer’s researchers to get a peek at the current state of testing. We found it a provocative read and figured our Blog readers would as well.

UK Researcher Knows Alzheimer’s Disease Firsthand

Cox begins his article by introducing us to Dr. Rebecca Sims, a neurogeneticist at Cardiff University, whose own firsthand experience of the pain of Alzheimer’s has echoed throughout her career. “My grandfather had Alzheimer’s,” she says, “so I’ve seen the devastation of somebody living with the disease. I’ve got friends as well whose family members have had other dementias.”

It’s not a surprise, then, to find Sims at the forefront of Alzheimer’s research. She has just completed the largest-ever genetic study of the disease, an international collaboration that has been ongoing since April 2022.

Cox explains, “The Cardiff research mined the genomes of more than 100,000 people around the globe – who either have the disease or had a parent who suffered from it – for tell-tale clues which point to why they were susceptible. All of which makes Sims perfectly placed to answer a particularly thought-provoking question – if there was a test which could tell you whether you were going to develop Alzheimer’s or not, would you take it?”

On Sim’s part, her answer is a strong no. The reason she is so adamant is because the disease is still incurable despite every attempt to study it. “It’s been in my family, but I don’t think I’d want to know,” she says. “At the moment, I wouldn’t see the benefit, if I’m honest. There’s nothing in place which would help me with that, so I think it’s better to just live your life and not worry about that too much.”

Genetic Research Makes Prediction More Accurate

But as our population around the world ages, and our understanding of the genetic and environmental risk factors for Alzheimer’s continues to deepen, the question is becoming more and more pressing, and the ability to predict it is becoming more and more viable.

“Alzheimer’s experts say that research has more than doubled the number of gene variants known to be associated with the disease, improving the accuracy of so-called polygenic risk scores which can be used to inform people about their potential of developing Alzheimer’s,” Cox writes.

The UK’s National Health Service (the Telegraph is a British publication) does not provide predictive tests for Alzheimer’s currently, but there are private tests available, including saliva tests offered by the genetic testing company 23andMe. “These attempt to provide a percentage likelihood by looking at whether individuals possess certain variants of gene called APOE, which has been heavily linked with the disease,” Cox explains.

But the results from Sims’s research could make forecasting Alzheimer’s even more accurate in the future, though researchers are careful not to estimate a timeframe. 

“We now have a total of 94 validated Alzheimer’s disease genes,” says Rudolph Tanzi, professor of neurology at Harvard Medical School. “We and others are trying to use all the Alzheimer’s disease genes as well as whole genome sequencing data from Alzheimer’s patients and family, with the goal of developing a reliable polygenic risk score for Alzheimer’s, beyond just APOE.”

Some Feel Advance Knowledge Will Help Families Plan

While some, like Sims, would rather not know, there are others who feel that the knowledge could be beneficial, so that individuals could make important life decisions at an earlier stage, well before the disease reveals itself.

“I had to spend the best years of my life with both parents suffering from dementia, which was hell,” says Cheryl Gearhart, a 56-year-old designer. “They had no plan for retirement, care or wills. If such a test was available for everyone, it would help them plan their future.”

In the field of medical ethics, some parallels have been drawn between advanced warning of Alzheimer’s and that of Huntingdon’s disease, an incurable neurological disorder caused by a single gene defect which can be diagnosed even before birth. Individuals with Huntingdon’s begin to develop symptoms between the ages of 30 and 50.

“If somebody has the gene for Huntington’s disease, they have a similar or worse prognosis than for Alzheimer’s,” says Dominic Wilkinson, professor of medical ethics at the University of Oxford. “What we know from that is that there are some people who do want to know that information for planning their life. Do they save up for a pension or spend their savings on travelling the world? But it’s important that people are aware of what they’re letting themselves in for before taking a test that might reveal such information. Some might want to live their life without having a Sword of Damocles hanging over them.”

Genetic Testing Can’t be Fully Accurate

But genetic factors only account for 60-80 percent of the risk for Alzheimer’s disease, adding complexity to forecasting properly. No genetic test could ever be 100 percent accurate. There are environmental factors, such as cognitive stimulation into old age, diet, smoking, exercise, and even isolation or loneliness, and these could never be accounted for precisely.

“It’s a complicated picture,” says Sims. “If you’ve got a high genetic risk of the disease, does that mean you’re going to get Alzheimer’s? The answer is no, because if you’ve got environmental factors that protect you, they can alleviate the cumulative effect of the genes. And vice versa: you can be at low risk genetically, but have some really high environmental risk factors in your life.”

There is also an issue of demographics. Most of our current understanding of the genetic landscape of Alzheimer’s comes from studies of white Caucasians, which could make tests in other ethnicities less accurate. “However,” Cox notes, “scientists like Sims and Tanzi are working on developing gender-specific and ethnicity-specific tests which also incorporate environmental data, for example whether a person is a lifelong smoker or not.”

He adds, “Sims believes that this additional information, combined with the levels of certain protein biomarkers in the cerebrospinal fluid – the colorless liquid in your brain and spinal cord – could one day lead to a test which can predict Alzheimer’s risk with an accuracy of more than 90 per cent.”

Sims says, “If we get to the point where we’re combining those different datasets, we might well be able to be more certain in our accuracy with regards to predicting who’s going to get the disease.”

Could There Be a Clinical Benefit to Advance Testing?

Will the National Health Service ever provide such a test? (The same question can be asked of Medicare in the U.S.) That depends entirely on whether it could be proven to provide clinical benefit, giving doctors the ability to prevent or slow the progression of the disease.

“Many Alzheimer’s experts argue that one of the reasons scientists have struggled to find medicines for the disease is because it is typically treated too late, once neurodegeneration has already set in,” Cox writes. “If tests can enable us to identify at-risk patients many decades earlier, treatments which attempt to prevent the accumulation of toxic proteins in the brain may well be far more effective.”

Colin Masters, an Alzheimer’s researcher at the University of Melbourne, says, “I believe that viable treatments are coming and then widespread testing will take off. We are looking to use an antibody therapy called aducanumab in patients with preclinical Alzheimer’s to try to prevent the onset of symptoms.”

Genetic Research Creates New Treatment Options

There’s further good news for how Sims’s research is changing the landscape: revealing new targets for treatment. “Immune cells called microglia, which are involved in the structuring and wiring of the brain, as well as how the brain handles inflammation, appear to be more heavily implicated in Alzheimer’s than previously thought,” Cox explains.

Sims says, “What the study showed us is that Alzheimer’s is not just about problems with toxic proteins accumulating in the brain, it is also a lot to do with how the brain fights inflammation and attack.”  If this means that treatments for the disease may be more accessible to develop than previously thought, Sims might reconsider taking an Alzheimer’s test, herself.

“If things changed and we got to a point where there were treatment options, I would take the test and I’d potentially take preventative medicines before getting symptoms,” she says. “But we’re not there yet.”

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