Our understanding of disease mechanism is also changing in a way that makes early diagnosis more valuable. Dementia has a very long preclinical stage – up to 20 years, in some cases – during which examinations and blood tests can detect subtle changes but symptoms have not yet appeared.
Two proteins begin to appear in the brains of patients with dementia during this time: tau and amyloid. Researchers have struggled for years to unravel the mystery of exactly what role they play, but now some believe they have an answer. In dementia and Alzheimer’s patients, amyloid forms tangles and plaques in the spaces between brain cells. The theory is that once it builds up to a certain level, it stimulates the tau protein – which is usually part of neuron scaffolding – to switch from a normal state to a toxic state. This is what causes the bulk of the symptoms, by killing the cells and interfering with the neurons’ ability to send clear signals.
In June 2021, a Food and Drug Administration (FDA) granted express approval to aducanumab, the first new Alzheimer’s drug in 18 years. It is designed to stick to amyloid particles and make it easier for the immune system to clear them. But it is a controversial approach, because in the past, drug treatments aimed at removing amyloid have failed to make much of a difference.
However, in the emerging dementia theory, the timing of the intervention may be very important. With better early detection, drugs like aducanumab can be given when they still have time to make a difference. “If you remove the amyloid at a very early stage, then perhaps the real benefit will occur,” Koychev says. If the amyloid can be removed from the brain before it causes tau to turn toxic, perhaps the worst effects can be delayed or avoided altogether.
Easy-to-use digital tests can be combined with brain scans and blood tests to help researchers build a map showing exactly how amyloid and tau proteins are linked to cognitive impairment — and whether removing them makes a difference. Rather than taking a blanket approach to screening everyone, Koychev suggests targeting the most at-risk groups with regular assessments.
However, he notes that there is still a lot of controversy in this area, and there is still serious doubts About whether a new Alzheimer’s drug will work as hoped. But it has reinvigorated research after what Habibie calls a “long drought” in an area that has lagged behind cancer in terms of investment and interest from drug companies. Denning thinks this is due to a combination of factors – the stigma of the disease, the advanced age of people who usually contract it, and the killer “well, that’s exactly what happens when you get old”.
Things are finally changing as a large and exciting demographic transitions to the age group where the risk is higher. Tests like the Mental Behavior Analysis Test are targeting them, but Koyshev hopes they will also “democratize access to brain health.”
Because it’s digital and only moderated, it can be taken anywhere you can take your iPad. This means that they can reach people who have been excluded from traditional studies of the condition, which are often populated by groups of volunteers that do not accurately reflect the underlying population. It can also be captured more often, to build a picture of an individual’s cognitive performance over time – Cognetivity has a separate iPhone app called OptiMind designed for home tests that aim to do this.
We may still lack good treatments for dementia and Alzheimer’s disease, but being able to detect them early could change our attitude toward them, which in itself may improve our understanding and spur investment in the solutions we need. “Brain health will become something people watch and take care of, just as you take care of your physical health,” Koichev says.
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