‘Amazing' reduction in Alzheimer's risk verified by blood markers, study says
Editor's Note:CNN Chief Medical Correspondent Dr. Sanjay Gupta and writer Sandee LaMotte are part of the study covered in this story and have written about their experiences.
When Penny Ashford's father was diagnosed with early-stage Alzheimer's disease at age 62, she knew the devastating brain disorder might one day steal her memory. In her late 50s, her free-floating anxiety turned to outright panic when she began struggling to find words.
'I couldn't tell a story. I couldn't get my words out,' said Ashford, now 61. 'I remember sitting at a dinner party one time, and I couldn't finish my thoughts. It was the most unbelievable moment.
'I came home and sobbed and told my husband, 'Something is wrong with me. I can't talk,'' she said. 'I was petrified.'
Today, after a complete revamp of her lifestyle and overall health, Ashford's struggles with retrieving words have eased, while measures of amyloid and tau proteins and neuroinflammation — all hallmark signs of Alzheimer's — have fallen.
Ashford knows about these improvements because she's part of a unique study tracking her progress via key blood biomarkers now being used to help diagnose early dementia. Instead of relying on painful spinal taps and expensive brain scans, these blood tests are heralded as a new, less invasive and time-consuming way to determine risk and aid in an earlier diagnosis of Alzheimer's.
The preliminary data, presented Monday at the American Academy of Neurology annual meeting in San Diego, analyzed biomarkers on 54 participants in an ongoing preventive neurology study called the Biorepository Study for Neurodegenerative Diseases, or BioRAND.
'The field is primarily using various biomarkers to determine if you have dementia or not,' said lead study author Dr. Kellyann Niotis, a preventive neurologist who researches risk reduction for Alzheimer's and Parkinson's diseases at the Institute for Neurodegenerative Diseases in Boca Raton, Florida.
'No one is really looking at the changes in these biomarkers as outcome measures, as a way of tracking progress in a person's journey to improve their brain,' Niotis said. 'We believe these biomarkers may show how the disease progression is being modified biologically by a person's actions.'
Alzheimer's blood tests are the key to widespread prevention of dementia, experts say. If people can be diagnosed in their doctor's office, they can more immediately move into preventive care and implement lifestyle changes designed to slow the progression of their disease.
The problem, said senior study author Dr. Richard Isaacson, is the variability in how well these new blood biomarker tests work to predict or track disease progression.
'There is a dirty little secret in the Alzheimer's blood testing community where so many testing platforms, biotech companies, and a flurry of new blood tests are released,' Isaacson said, 'but it's unclear which of these tests are most accurate to track progression and evaluate response to therapies to slow progression toward dementia.'
To address this gap, Isaacson's research team and collaborators at five sites across the United States and Canada set forth to evaluate and eventually cross-compare the clinical use of what the neurologist said he believes will one day become 'the cholesterol test for the brain.'
'In the not so far future, people in their 30s, 40s, 50s, 60s and beyond will get a baseline test to evaluate risk and help track progress over time — similar to how traditional cholesterol tests are used today,' said Isaacson, founder of one of the first Alzheimer's prevention clinics in the United States.
'Our eventual goal is to offer a blood panel at cost to help democratize access and broaden the ability for people to receive care,' he added.
Measuring levels of both amyloid and tau is key to understanding and diagnosing Alzheimer's and other forms of dementia.
Amyloid plaques play a key role in the development of Alzheimer's when small clusters gather at synapses in the brain and interfere with the nerve cells' ability to communicate. Such plaques are thought to trigger changes in tau proteins, which form into tangles in parts of the brain controlling memory.
Tau tangles are also implicated in other neurological diseases such as frontal lobe dementia, or FTD, and Lewy body dementia in which abnormal clumps of a protein called alpha-synuclein accumulate in the brain's neurons.
The biomarker plasma phosphorylated tau 217, or p-tau217 for short, is a top contender in the diagnosis of mild cognitive impairment and early-stage Alzheimer's disease. Its cousin, p-tau 181, is also a helpful indicator.
P-tau 217 is a 'beautiful marker for Alzheimer's,' Dr. Maria Carrillo, chief science officer of the Alzheimer's Association, told CNN in an earlier interview.
'You're not really measuring amyloid, but the test is telling you it's there, and that's been backed up with objective PET (positron emission tomography) scans that can see amyloid in the brain,' Carrillo said. '… If you have elevated tau in your brain, however, then we know that's a sign of another type of dementia.'
Another biomarker test is the amyloid 42/40 ratio scan, which measures two types of amyloid proteins, another key biomarker of Alzheimer's disease. At times, such tests work best when used together. In an earlier study, a combination of both amyloid and p-tau 217 tests, called the amyloid probability score, showed a 90% accuracy rate in determining whether memory loss is due to Alzheimer's disease.
Glial fibrillary acidic protein, or GFAP, and neurofilament light chain, or NfL, which indicate brain inflammation and degenerative decay, are also helpful in tracking the progression of Alzheimer's disease. Dozens more biomarkers are being tested in labs around the world.
Isaacson's team at the Institute for Neurodegenerative Diseases is studying more than 125 individual markers from a variety of commercial and research-based tests, some of which may soon be available in a clinical setting.
Why investigate so many? Because personalized medicine may demand it, Niotis said.
'Neurodegenerative diseases present so differently in different people,' she said. 'It may be we will need a very nuanced, individualized approach in clinical practice to monitor the effectiveness of what we're doing for a given patient.'
The ongoing preventive neurology study called BioRAND reported on 71 participants, with biomarkers being analyzed on 54 people. The other 17 people served as the control group.
The group of 54 received a series of personalized lifestyle recommendations designed to improve their brain. Such interventions have been shown in past research to improve memory and thinking skills by five points on a cognitive test for people with mild cognitive impairment.
The recommendations include a focus on blood pressure control, diet, exercise, stress reduction, sleep hygiene and weight control as well as addressing metabolic, hormonal and nutrient imbalances. Medications, vitamins and supplements are tailored to each person's unique needs.
Similar to a 2019 study led by Isaacson and Niotis, people who fulfilled at least 60% of the lifestyle recommendations were considered high compliance, while those who implemented less than 60% were low compliance. Periodic blood tests tracked progress in various brain biomarkers.
The outcome? The more work people put into change, the better their brains. Just look at Penny Ashford.
'My blood work was terrible; my eating habits were terrible. I didn't exercise, so my muscle tone was really bad — I had no muscles in my bottom or on my thighs,' Ashford said.
'I got the lecture of a lifetime,' she said. 'They told me, 'Your window is closing, your markers are so bad. Either you've got to do this, or you're done.''
A lifelong sugar addict, Ashford stopped eating sweets.
'I used to think I had a chemical imbalance because I was such a crazy freak about sugar — I could polish off a whole bag of Oreos, no problem, and I love ice cream,' Ashford said.
'I haven't had a dessert. I haven't had ice cream. I haven't had anything except fruit since a year ago March.'
She began an intense exercise program of cardio and resistance training, along with yoga for stress reduction, and moved to a plant-based Mediterranean style of eating. Under a doctor's supervision, she added supplements and vitamins to boost energy and lower stress.
'She was a 10 out of 10 with her diet and exercise,' Niotis said. 'She lost around 30 pounds and gained lean muscle mass. It was amazing.'
A year later, Ashford's blood biomarkers told a completely different story about her brain health. Her p-tau 217 dropped by 43% and her p-tau 181 by 75%.
'We also looked at GFAP and neurofilament light, the markers of neuroinflammation and neurodegeneration,' Niotis said. 'Penny's GFAP went down by 66% and her NfL went down by 84%.
'These are really impressive changes in these markers of neuronal health,' she said. 'And the best part about it is it really did track with her clinical symptoms. Her word retrieval problems improved, and she felt so much better.'
Ashford wasn't the only top performer in the study. Blood biomarkers also significantly improved across the entire group given risk reduction advice, Isaacson said, even those who were not as committed as Ashford.
'I've lost count on how many people have shown blood markers of brain disease trend in the right direction, but every time it amazes me,' he said. 'For over 20 years, I was told that what is happening right in front of my eyes was impossible, but the patients' stories, clinical improvements and test results speak for themselves.'
Much more work remains before blood testing for Alzheimer's becomes a routine part of clinical practice, Isaacson said.
'Our group has a saying, 'Promise not to overpromise.' By this we mean it's critical to be transparent about the current limitations of these tests, and the variability across different platforms,' he said.
While science works out the kinks, Ashford counts herself lucky to be able to track changes in her biomarker numbers — a key motivator in her journey toward better brain health.
'It's huge, huge,' she said. 'I'm so proud of myself. And each success that I have empowers me to do more, keep going and not let up.
'I look back at my dad. He didn't have any of these options. I watched my dad deteriorate, and I thank God, I am so lucky. We are so lucky.'
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