Cambridge Vision Technology utilises AI-based technology to detect Alzheimer’s disease early on by using ocular biomarkers. They emphasise the importance of early detection of dementia to improve clinical outcomes for disease therapies and to maximise the economic and societal impact of this innovative new technology
In 2023, dementia was the single largest cause of death in the UK. Despite its prevalence, one in three people remain unaware they have it, and of those diagnosed, only 2% will ever receive a gold-standard imaging diagnosis. The past 18 months have seen the emergence of new therapies. For the first time, we are transitioning from an observational to an interventional clinical regime in how we approach dementia.
These new therapies are disease- modifying treatments (DMTs). They need to be administered early to be effective. Historically, dementia, including Alzheimer’s disease, has been diagnosed through cognitive tests, which evaluate memory, problem- solving, and other mental functions. However, early detection remains a significant challenge, likened to finding a needle in a haystack, due to the subtle and varied onset of symptoms.
Early detection is crucial not just for these recently approved therapies but also for the pipeline of therapies currently in development. Here, we present the case for early detection as an essential capability in the development and deployment of dementia treatment therapies.
Disease-modifying therapies
The past 18 months have seen the approval of two different DMTs for the treatment of Alzheimer’s disease, the most common cause of dementia.
- Lecanemab (Leqembi): This drug received accelerated FDA approval on January 6, 2023, followed by traditional approval in July 2023.
- Donanemab (Kisunla): This drug obtained FDA accelerated approval in July 2024.
The idea behind DMTs is that these therapeutics interfere with the biological processes of Alzheimer’s to slow disease progression—both lecanemab and donanemab target amyloid-beta plaques in the brain.
These therapies slow the progression of the disease by clearing these plaques. Research indicates that these treatments can slow progression by about 30%, extending the mild phase of the disease from three to four years.
Detecting Alzheimer’s disease at an early stage is crucial. If we can do so, we can administer the drugs early and maximise their efficacy.
The need for early detection of dementia
Alzheimer’s disease begins affecting the brain for years, even decades before symptoms become apparent. By the time noticeable cognitive decline occurs, significant neuronal damage and loss have already occurred. Early intervention aims to slow down or halt this process before extensive damage occurs, potentially preserving cognitive function for a longer period.
There is a critical window during which DMTs are most effective, at the early stages of Alzheimer’s, when patients have mild cognitive impairment (MCI) or early dementia. Treatments are less effective in the later stages of the disease when neuronal loss and brain atrophy have already occurred.
Recent results support this. In the TRAILBLAZER-ALZ 2 Phase 3 study, two separate groups were given donanemab:
- Group 1: A general group where cognitive decline had manifested, and the participants were at medium- advanced stages of progression.
- Group 2: A smaller group where progression was less advanced.
The individuals who were less advanced in the disease experienced the strongest results. The results showed a 35% reduction in cognitive decline for the low/medium decline group compared to 22% for the general group receiving donanemab compared to a placebo. This trial underscored the importance of early detection, as those at earlier stages experienced greater benefits from the treatment.
The future therapy pipeline
Looking at the wider sector of therapeutic development for Alzheimer’s disease, we see that the need for early detection extends beyond lecanemab and donanemab. As of April 2024, there were 127 therapies in 164 clinical trials, with 75% of these therapies being disease-modifying treatments.
While donanemab and lecanemab target amyloid-beta plaques, other therapies in development operate on different mechanisms. Let’s look at two other therapies in development.
- BIIB080: Currently in Phase 2 trials, this therapy directly targets tau tangles in the brain.
- NE3107: Currently in Phase 3 trials, this therapy aims to reduce neuroinflammation while maintaining beneficial functions.
These emerging drugs are crucial in the fight against dementia. While Alzheimer’s disease constitutes 60-70% of all dementia cases, other forms of dementia could also benefit from these therapies. For instance, tau pathology affects frontotemporal dementia, and neuroinflammation impacts vascular, Lewy body, and frontotemporal dementia in addition to Alzheimer’s disease.
The Importance of biomarkers
Detection using biomarkers, such as amyloid and tau proteins, is a relatively new development, and the current technologies are not yet capable of population-level application. While these biomarkers help identify the risk of disease onset early, existing solutions are prohibitively expensive and unscalable. Machine Learning (ML) has already begun democratising healthcare in other clinical applications, presenting a substantial opportunity to enable early, widespread early detection of dementia.
Beyond pharmacological treatments, early detection of dementia offers several benefits. It enables individuals to begin health measures such as increased social engagement, which can help maintain cognitive function and allow for the management of comorbidities like hypertension. Early detection also provides time for patients and their families to plan for financial support and long-term care, alleviating future burdens.
The future holds great promise for treating dementia, with the recently approved drugs representing just the beginning. In order to maximise the effectiveness of these therapies, we need scalable, low-cost early detection methods that provide population-level screening. Advances in Artificial Intelligence and diagnostic tools are providing new opportunities to solve the early detection problem, making this an exciting time in the fight against dementia.
This work is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International.
