Alzheimer’s - Hope on the Horizon

Introduction

Alzheimer’s disease (AD), along with other forms of dementia, is currently the leading cause of death in the UK. It causes profound, progressive decline in cognitive, physical and emotional health. Its effects are felt not only by the individual, but by their friends and family too. Although current medications given under the NHS can help improve symptoms, these cannot prevent disease progression. However, recent advances in pharmacological therapies could provide hope for those affected by AD.

What is Alzheimer’s Disease?

AD is the most common cause of dementia worldwide, accounting for approximately 60-70% of cases. Its cause, although not fully understood, is linked to the accumulation of amyloid and tau proteins in the brain. This disrupt communication between brain cells, and ultimately leads to cell death. This protein accumulation is paired with reduced levels of neurotransmitters, notably acetylcholine, further impairing intercellular messaging. Together, these processes lead to symptoms such as memory loss, confusion, difficulty with daily tasks and personality changes. As the disease progresses, increasing loss of neurological function indirectly contributes to mortality, most commonly through complications such as infections, falls, and frailty-related decline.

How is it currently managed?

Current medication management through the NHS can only improve symptoms, rather than prevent or reverse disease progression. These include:

• Acetylcholinesterase (AChE) inhibitors (donepezil, galantamine and rivastigmine) - these increase levels of the neurotransmitter acetylcholine by preventing its breakdown, and are typically used for mild to moderate disease.

• Memantine - this works by inhibiting the effects of excessive amounts of glutamate, a chemical found in the brain, and is used for more severe disease.

• Antipsychotics and antidepressants - these can be offered to help with the behavioural and psychological symptoms associated with AD.

In addition to medication, non-pharmacological therapies such as cognitive stimulation therapy, physical therapy and social engagement, also play important roles in managing AD and improving quality of life.

Disease-Modifying Therapies

In recent years, new monoclonal antibody therapies have emerged which target the amyloid protein pathway in early AD. Lecanemab and donanemab have been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for treating mild or early stage AD. These agents are given intravenously at regular intervals, and work by promoting the clearance of amyloid proteins from the brain. Their results are promising, with lecanemab and donanemab slowing cognitive decline by approximately 27% and 22-35% respectively. However, treatment requires careful and frequent monitoring due to the risk of amyloid-related imaging abnormalities (ARIA), including brain swelling and small areas of brain bleeding. As a result, regular MRI monitoring is required. Genetic testing is also required, as individuals with the APOE ε4 gene carry a higher risk of treatment-related complications.

The Cost and Access Barrier

Despite MHRA approval, both donanemab and lecanemab were deemed unsuitable for NHS use by the National Institute of Health and Care Excellence (NICE). This decision was based on assessment of their cost-effectiveness. The medications alone are estimated to cost between £20,000 and £25,000 per person each year. Additionally, substantial healthcare infrastructure costs would be incurred, including frequent hospital admissions for treatment administration, ongoing patient monitoring, as well as specialist genetic testing. NICE therefore determined that their modest benefits do not justify their high treatment and monitoring costs. This decision has been subject to ongoing appeal and review.

Emerging Medications

There are also a number of therapies currently being developed with the objective of slowing AD progression. These include:

• Remternetug - like donanemab and lecanemab, this monoclonal antibody therapy targets amyloid proteins. However, its intramuscular administration route makes it a potentially more patient-friendly and cost-effective alternative to its intravenous predecessors. Early data from the phase 3 trial is promising, finding remternetug to be accessible and well tolerated. Long-term clinical outcomes remain under investigation.

• Hydromethylthionine mesylate (HMTM) - this medication targets tau proteins and can be given orally, preventing the need for infusions or needles. Clinical trial data has shown mixed results, but more definitive data is needed to determine its effectiveness.

• Blarcamensine - this new oral drug targets sigma-1 receptor pathways, helping cells to clear toxic accumulation of waste products. Trial data showed a reduction in decline in memory and thinking scores, but no improvement in participants’ ability to perform daily tasks. Regulatory approval has not yet been granted.

• Trontinemab - this monoclonal antibody drug has been designed to improve blood-brain barrier penetration, improving the delivery of amyloid-targeting therapy to the cells. It is currently in late-stage clinical trials, with results expected in coming years.

The Horizon of Future Treatment

Although AD remains a progressive and currently incurable disease, the therapeutic landscape is evolving. The emergence of monoclonal antibody therapies has shifted treatment from purely symptomatic towards potentially slowing the underlying pathology. However, these advances remain limited by their modest results, challenges regarding access, safety considerations and cost-effectiveness.

Ongoing research into alternative pathological targets continue to shape future directions. As our understanding of AD improves, there is cautious optimism that new medications and treatment pathways may deliver more significant clinical benefits. These offer the hope that there may be a change in the trajectory of this condition for future generations.

References:

1) Alzheimer’s Society. Researching New Drugs for Alzheimer’s disease. Available at: https://www.alzheimers.org.uk/what-we-do/researchers/news/researching-new-drugs-alzheimers-disease (Accessed 03/03/2026).

2) World Health Organisation. Dementia. Available at: https://www.who.int/news-room/fact-sheets/detail/dementia (Accessed 04/03/2026).

3) NHS website. Alzheimer’s Disease - causes. Available at: https://www.nhs.uk/conditions/alzheimers-disease/causes/#:~:text=Alzheimer's%20disease%20is%20thought%20to,or%20language%20rather%20than%20memory. (Accessed 04/03/2026)

4) Alzheimer’s Research UK. Donanemab. Available at: https://www.alzheimersresearchuk.org/dementia-information/treatments-for-dementia/donanemab/ (Accessed 04/06/2026)

5) Neurology Live. 01 December 2025. Early Phase 3 Data Highlight Convenience and Feasability of Self-Administered Alzheimer’s Agent Remternetug Available at: ylive.com/view/early-phase-3-data-highlight-convenience-feasibility-self-administered-alzheimer-agent-remternetug (Accessed 05/06/2026)

6) Alzheimer’s Research UK. 16 December 2025. CTAD 2025: Six highlights from the latest clinical trials in Alzheimer’s Disease. Available at: https://www.alzheimersresearchuk.org/news/ctad-2025-six-highlights-from-the-latest-clinical-trials-in-alzheimers-disease/ (accessed 05/06/2026)

7) National Institute for Health and Care Excellence (NICE). 19 June 2025. Final draft guidance finds benefits of 2 Alzheimer’s treatments remain too small to justify the additional cost to the NHS. Available at: https://www.nice.org.uk/news/articles/the-benefits-of-alzheimers-treatments-donanemab-and-lecanemab-remain-too-small-to-justify-the-additional-costs-says-nice-in-final-draft-guidance (Accessed 10/06/2026)

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