Alzheimer’s disease - early diagnosis and how we will delay onset and slow progression
Wicking Trust 2020 Symposium:
An update from Professor Colin Masters AO, Wicking Strategic Review Panel member
Hoped for medical advances for Alzheimer’s Disease have been set back in part this year by some disappointments in trials and disruption from the coronavirus pandemic but a leading global dementia researcher believes important breakthroughs are largely still on track.
“I’m biased of course, but for me there is a general feeling of optimism,” Prof Colin Masters AO, a world leader in research into Alzheimer's disease and viral infections of the brain, told the recent 2020 Wicking Trust Symposium.
Prof Masters delivered a global and Australian update on the latest research developments on Alzheimer’s disease to the online symposium, saying hope and interest is focused on promising developments in diagnostics and therapeutics areas.
A member of the Wicking Trust Strategic Review Panel, he is also optimistic about the work in Australia of the newly formed Australian Dementia Network (ADNeT) that is developing a clinical quality registry (CQR) for dementia and Memory Clinics that will harmonise diagnosis and move people more quickly into clinical trials, much like in cancer research.
Prof Masters, who is Laureate Prof of Dementia Research at the Florey Institute and The University of Melbourne, is distinguished for work over decades that has had a major influence globally on Alzheimer's disease and other neurodegenerative diseases.
He is known particularly for collaborative studies conducted with Konrad Beyreuther in which they discovered the proteolytic neuronal origin of the beta-amyloid protein (Aβ) which causes Alzheimer’s disease.
He told the symposium this work indicates that the build-up of beta-amyloid in the brain is a process that starts silently about 30-40 years before outward signs of dementia, like memory loss or cognitive decline, have begun.
“Intervening in those years before the disease is at the upper threshold (of build-up) is the name of the game at the moment… if we’re going to prevent Alzheimer’s disease”, he said.
Prof Masters said not all dementia researchers accepted the amyloid theory but, in a timely comment, said: “That’s the way science works. It’s a discipline where freedom of thought is the norm.”
However, he was buoyed by research published in Nature magazine in January 2019, showing it was possible to use a novel biomarker to accurately quantify minute traces of beta-amyloid from a teaspoonful of blood and gauge the progression of Alzheimer’s.
The blood test measures a specific peptide in the blood to inform scientists, with 90 per cent accuracy, if a patient has the very earliest stages of Alzheimer’s disease, giving the potential to eventually disrupt expensive and invasive scanning and spinal fluid technologies.
He told the Wicking Symposium that the discovery had sparked a race by about a dozen companies and research groups from around the world, led at this stage by Shimadzu and C2N.
“That’s on everyone’s mind at the moment: can we establish a reliable blood test that can be used to screen large numbers of people to get them into clinical trials early enough so we can start seriously thinking about prevention,” he said.
“The answer to that is yes, it’s looking like we can,” he said, adding that experts expect at least one or more of these companies to deliver a viable test “within the next year or two”.
Prof Masters also holds high hopes that researchers will develop a prognostic test for Alzheimer’s off the back of exciting new research led by Melbourne researchers Yen Ying Lim at the Florey Institute in Melbourne and Paul Maruff of Cogstate, a neuroscience technology company.
Their fascinating work has indicated that cognitively normal people who tested positive for brain amyloid learned fewer Chinese characters over a six-day period than their amyloid-negative peers.
That suggests that learning tests could be used to more sensitively detect emerging cognitive deficits in the earliest stages of the disease than memory tests, “quicker than your partner noticing you are starting to have memory lapses”, he said.
On the therapeutic side of research, Prof Masters said much work was underway by pharmaceutical companies globally to discover and test drugs to treat early-stage Alzheimer’s disease, when only mild cognitive impairment had occurred.
An international clinical trial evaluating whether two investigational drugs can slow memory loss and cognitive decline in people in the early stages of Alzheimer’s disease yielded disappointing results earlier this year, however he said work goes on.
“That’s the sweet spot at the moment,” Prof Masters said of early stage intervention, likening it to screening for prostate and breast cancer.
“We’re taking a very similar approach now in Alzheimer’s disease, where we understand enough about the molecular causes to think we can intervene and intervene early.”
“Our best hope at this point is that, if you give these powerful drugs at an early enough stage, you will delay onset,” he said, acknowledging that there was still no hope of breakthroughs that could reverse Alzheimer’s disease.
As with so many areas of life, Prof Masters said research into dementia and Alzheimer’s disease had been disrupted by the coronavirus pandemic, more so in the United States but also in Australia.
The Florey Institute, which was subject to Melbourne’s lockdown for many months, is the world’s largest single site for the A4 study (Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease), an ongoing prevention trial launched in 2014 to test whether the drug solanezumab could slow cognitive decline.
“[The pandemic impact] hasn’t been devastating but we had the trial on hold for a month or two,” Prof Masters said, explaining that recruitment for studies globally had been harder amid general fears of COVID-19 and a reluctance by people to visit hospitals.
Prof Masters dashed hopes of the role of lifestyle factors in preventing Alzheimer’s disease, saying it was “one of the myths in the lay press at the moment”, although lifestyle obviously played a role in many other important conditions, including vascular dementia.
The incidence of dementia is declining, principally because of lower rates of smoking and cardio vascular disease, and better control of hypertension and diabetes, but “to the best of my knowledge, there is no evidence that dietary intervention impacts on the risk of Alzheimer’s disease” he said.
Prof Masters conceded that many of his colleagues would be “up in arms” against him for saying that and he agreed there was early evidence that diet, exercise and sleep do have some relationship to the build-up of amyloid protein on the brain.
“But today they are only association studies, we cannot demonstrate causality,” he said. “All I can say now is the evidence is strongly behind genetic determinants for Alzheimer’s disease, and environmental determinants are currently very hard to identify.”