Breakthroughs Changing The Diagnosis And Treatment Of Alzheimer's

Forbes

a day ago

Jerry Klauer, an Alzheimer's patient who received a recently approved therapy to treat the disease, ... More pictured last year in Florida with his wife Jana, a retired physician.
In 2012, Phyllis Barkman Ferrell experienced a profound irony. The longtime veteran of Eli Lilly was leading a team preparing to launch a groundbreaking molecule to treat Alzheimer's when her own father was diagnosed with the disease.
He became one of approximately 500,000 people diagnosed in the United States with the disease that year. Globally, over 10 million cases of dementia are diagnosed each year, with Alzheimer's contributing a large portion of the burden.
Though Ferrell had rare access to top leaders working in the field, her father's path to a diagnosis was not straightforward, and never actually became clear. He spent a week in the hospital and endured a lumbar puncture and the insertion of a shunt in his brain. A PET scan, which can detect abnormal changes in the brain consistent with Alzheimer's disease, cost $10,000 and was not covered by insurance.
When Ferrell asked a resident at the hospital to give her father an amyloid test, the resident responded, 'What's an amyloid test?' Amyloid refers to a protein that misfolds and accumulates pathological deposits in the brains of people with Alzheimer's disease.
'Imagine if I could have given him a blood test to see if he had amyloid,' says Ferrell, 'rather than a lumbar puncture and brain surgery?'
In fact, that is exactly what has become available – along with two disease-modifying therapies.
The New Alzheimer's Workup
Today, if patients present with symptoms of memory loss to their primary care provider, they can be referred to a workup for Alzheimer's at a memory clinic with tools that weren't available even three years ago.
'We just got on base at a game that nobody had ever gotten a hit before,' says Ferrell, who now works with the Davos Alzheimer's Collective, a global public health initiative working to improve patients' access to the new innovations.
In the new workup, patients can take a digital cognitive assessment, which compares their performance to a standard database. If the patient has a reasonably high chance of having Alzheimer's based on their presentation, then a blood-based biomarker test can be 'very good' at informing the diagnosis, says Dr. Greg Cooper, chief of adult neurology and director of the Memory Center at Norton Neuroscience Institute in Louisville, Kentucky.
Jeff Burns, neurologist who co-directs the Alzheimer's Disease Research Center at the University of Kansas in Kansas City, has seen clinicians in his health system order 600 of the blood tests in 11 weeks since the in-house test became available, a sign of their high demand. 'They're very useful in the right context,' he says, adding that he would like to see their use increase in primary care, since memory clinics are 'overloaded' with patients. In Kansas, for instance, there's only one such clinic in the state.
If the blood test is positive, patients can go for an insurance-approved PET scan or spinal fluid testing to determine if they are eligible for the new drugs. If the amyloid diagnosis is confirmed, patients can be prescribed one of two monoclonal antibodies, both FDA-approved in 2023, that can slow disease progression by targeting and removing pathological amyloid deposits in the brain.
'It's the first time we can actually alter the trajectory of disease,' Cooper says.
A Patient Story
Jerry Klauer, 83, is living proof of this remarkable paradigm shift. Several years ago, his wife Jana, a retired physician, began noticing a troubling change in his memory. He was forgetting dates and plans, though he had been impeccably on time before. He also struggled to recall recent events, and his driving became unsafe.
Through a connection at the Alzheimer's Drug Discovery Foundation, Jerry got diagnosed with Alzheimer's after a positive blood-based biomarker test and a PET scan confirmed high amyloid buildup. He then became eligible to join a clinical trial of one of the monoclonal antibodies (which has since been FDA-approved).
'I was very fortunate to get into the program early,' says Jerry, who is a co-founder of the Wall Street boutique investment firm Gerard Klauer Mattison and Company. Though he acknowledges that the drug is not a cure, it reduced his amyloid and improved his symptoms.
Before he started the drug, his amyloid had to be in a certain high range to qualify. Now, his amyloid measures in the normal range.
'He's stable,' Jana says. 'If he wasn't doing this, he would be getting worse. Is his memory what it was when he was 30 or 40 years told? No, but he lives his life. It's a wonderful life.'
Early Intervention Matters
Jerry's Alzheimer's disease was not very advanced when he started the monoclonal antibody. That is when the medicine can be most effective.
'In the past,' says Greg Cooper, 'although wrong, people had a nihilistic approach, saying why should I be in a hurry to get a diagnosis? Now the urgency for a diagnosis is compelling.'
A major question the field is seeking to answer is just how early does it pay to get diagnosed?
The pathological changes in the brain from Alzheimer's start 15 to 20 years before symptoms begin. Current clinical trials that read out in 2027 are testing whether patients who have confirmed amyloid, but zero cognitive decline, stand to benefit from the monoclonal antibodies.
Burns predicts that if a benefit is substantiated, there will be a major paradigm shift in screening for Alzheimer's disease. 'It could be coming quickly if the trials of the new drugs work to reduce risk in this population. And if they do, then we will be in a whole different world. Then everyone over 65 should be screened.'
That said, amyloid is not the whole story on preventing or delaying Alzheimer's onset. It's an early feature, but removing amyloid only slows, not stops, the disease.
'The focus now is can we stop or slow tau from accumulating?' Burns explains.
Tau is a protein that builds up in dead or dying neurons in Alzheimer's disease, and it spreads through the brain. First the amyloid buildup starts, and appears to accelerate the tau. 'So pulling the amyloid out looks like it slows the tau accumulation, but doesn't stop it,' says Burns. An experimental drug in phase 2 clinical trials uses a new approach to reduce the accumulation of tau.
'The tau comes much later than the amyloid,' explains Donna Wilcock, Director of the Center for Neurodegenerative Disorders at Indiana University School of Medicine. 'Amyloid usually precedes the detection of tangle pathology by maybe 10 years. So we may have a 10-year window of catching that amyloid before it starts downstream tau.'
In the last decade, researchers have learned that there is a tipping point at which the tau pathology is self-propagating, and the presence or absence of amyloid doesn't affect the tau – dubbed the 'cataustrophe.'
'It seems as though the earlier we can get these amyloid-lowering therapies into patients,' Wilcock says, 'the better the outcome.'
What You Can Do To Lower Risk
All the experts interviewed for this article stressed the importance of healthy lifestyle habits, which may prevent up to 45.3% of all dementia cases according to the Lancet Commission. These factors are essential: controlling hypertension, blood sugar, and cholesterol, getting regular exercise and seven to eight hours of quality sleep, having an active social life, and eating a largely plant-based Mediterranean diet.
'Controlling a lot of these factors in the mid-life period has the biggest impact on how they affect your risk for dementia later in life,' says Wilcock. 'Mid-life untreated hypertension greatly increases your risk for dementia later in life.' Her own blood pressure started rising in her 40s, and she pushed her primary care doctor to manage it aggressively, noting that she had to 'self-advocate' to get her doctor to take it seriously.
'Through better brain health and attention to modifiable risk factors, how can we eliminate half of dementia before it ever starts?' asks Greg Cooper. 'And for other half, how can we identify it and successfully intervene before we ever have symptoms? It may sound hyperbolic, but I can at least imagine that day.'
Jeff Burns concurs that it's an optimistic time for the field, with a broader array of approaches in development than ever before. As of 2023, there were over 140 drugs in clinical trials for Alzheimer's.
For patients like Jerry Klauer, breakthrough science is already a clinical reality. Such encouraging experiences and the rapid pace of advancements over the last few years gives me great hope that one day, this terrible disease itself will be long forgotten.Thank you to Kira Peikoff for additional research and reporting on this article.