Breakthroughs In Dementia Research: Promising New Treatment Approaches

Overview

Dementia is an umbrella term encompassing a range of neurodegenerative diseases affecting memory and cognition, the most common and widely known being Alzheimer’s disease. The disease causes progressive shrinking of specific brain areas, causing brain cells to die and impacting the rebuilding of those important connections. Currently, there is no ‘cure’ for dementia, and its complexity and various subtypes mean it is unlikely there will ever be one.¹ Nevertheless, new treatment options are continuously advancing to extend patients’ life expectancy and improve their quality of life. This article will explore the recent breakthroughs within dementia research including drug therapies and immunotherapy which have proven to treat the symptoms of dementia.

Introduction

Understanding dementia

Dementia is an age-related disease primarily causing loss of cognitive function (processing thoughts), which affects memory, language, and personality, interfering with a person's day-to-day functioning.² Many subtypes of dementia exist including Vascular dementia and Lewy-body dementia, however, Alzheimer’s disease accounts for 60-70% of all cases.³ The disease begins with episodic memory loss greater than expected with normal ageing. This is because the disease causes nerve cells of the hippocampus (involved in memory, learning, and emotion) to die and shrink in this area of the brain. Other symptoms can include misplacing things, being confused in familiar places, and getting lost when walking or driving; however, symptoms affect each person differently depending on the underlying cause and other health conditions someone may have. 

Most dementia subtypes are caused by the accumulation of ‘senile plaques’ which is a cluster of misfolded proteins, in the case of Alzheimer's disease these are amyloid-beta protein plaques and neurofibrillary tangles made of tau protein. These plaques are toxic to the brain and interfere with signalling and communication between cells in the brain. Age and genetics are the biggest non-modifiable (out of our control) risk factors for dementia. However, there are a few modifiable (those we can change) risk factors which include smoking, hypertension (high blood pressure), alcohol, diabetes, and obesity. Awareness of the modifiable risk factors is important in preventing the number of people diagnosed with dementia.

Importance of breakthroughs in dementia research 

We live in an ageing population, which means the proportion of elderly people has increased over the years. This is due to many reasons such as the continued decline in fertility rate and the increase in average life expectancy. Although people living longer is a positive thing, people not remaining healthy at older ages may develop multiple conditions at once, placing a strain on the healthcare system. Currently, 944,000 people are estimated to be living with dementia in the United Kingdom, and the number is predicted to grow to 1.1 million by 2030.⁴

This is partly due to population ageing, causing the disease to remain a public health concern. It not only impacts the individuals but also impacts our society and economy. It is therefore important to fund further dementia research to support those living with the illness as well as families, carers, and society as a whole. 

Drug therapies

Currently, the treatments available for dementia and Alzheimer's are ‘symptomatic treatments’ used to treat the symptoms of the disease, rather than halt the disease from becoming worse. The goal of the research has recently been to identify drugs that are ‘disease-modifying treatments’ (DMTs), which would effectively slow the progression of mild cognitive impairment and dementia. Researchers have developed these drugs to clear the toxic amyloid proteins from the brain and stop them from clustering. These drugs are called immunotherapies and are already used to treat cancer utilising the body’s immune system to remove foreign proteins.  

There are currently no licensed DMTs in the UK but a select few are in the stages of development and approval by the National Institute for  Clinical Health and Excellence (NICE) to see which would be appropriate for use within the NHS:⁵

Donanemab 

A recent trial called ‘TRAILBLAZER-ALZ2’ included 1182 patients with amyloid in the brain and administering the drug Donanemab by intravenous drip once a month. The drug was shown to slow down the decline in memory and thinking by 35% in those with early-stage Alzheimer's disease and slowed the decline of everyday activities such as driving and managing finances by 40%.⁶ The trial also showed the drug cleared plaques from the brain. 

The drug is developed by Eli Lilly, a US pharmaceutical company and is awaiting approval in the UK.⁷ Evidence from the trial suggested the drug was most beneficial in earlier stages of the disease; however, future trials are underway to establish whether Donanemab can prevent the development of Alzheimer's and compare effectiveness against other drugs.

Lecanemab 

This breakthrough immunotherapy drug is marketed under the name of ‘Leqembi’ and was developed by the pharmaceutical company Eisai. Similarly to Donanemab, it is also administered by intravenous drip every two weeks and curated for those in the early stages of Alzheimer's disease. The Clarity-AD trial consisted of 1795 patients and showed Lecanemab to successfully remove amyloid and tau proteins from the brain of people with dementia - with a decline in thinking and memory skills slowed by 27% and decline of quality of life slowed by 56%.⁸ For this drug to be available in the UK it must be approved by the Medicines and Healthcare Products Regulatory Agency (MHRA). This process is currently underway with the hope of making the drug available within the NHS, depending on how cost-effective the treatment is. The drug could be available as soon as 2025.

Remternetug 

Remternetug is the third of the most recent breakthrough immunotherapy drugs, also produced by Eli Lilly. It is expected to potentially perform better than Donanemab as it is a ‘second-generation’ drug, targeting the same type of amyloid plaques with amyloid clearance achieved in 75% of patients receiving doses.⁹ In this trial of Remternetug, the drug was administered via injection under the skin for comparison of effectiveness against other immunotherapy drugs and is a more practical method of administration. Remternetug was tested on more mild to moderate cases of Alzheimer's and showed faster clearance of amyloid (6 months) compared to Donanemab (18 months). 

Summary

The recent breakthroughs in dementia drug interventions are exciting and promising for patients in the UK. It has been established that lowering amyloid beta levels in the brain is the key to future drug-modifying development. A drug effective in slowing the progression of the disease would make a big difference to the quality of life, independence, and cognition of people living with dementia, as well as a better disease prognosis. Still, some considerations have to be made. 

The treatments offer potential side effects such as amyloid-related imaging abnormalities (ARIA), which can cause brain swelling and bleeding however, 80% of people who did experience side effects did not develop this.¹⁰ Furthermore, due to the majority of the new drugs being administered via intravenous routes, the accessibility of treatment must be considered,d as it may not be suitable for all patients. For example, having to visit the hospital frequently for those experiencing dementia symptoms may be challenging, so the future development of a drug with at-home administration would be more suitable.

The majority of the breakthrough drugs are more effective in the earlier stages of dementia, making early diagnosis essential to providing the best intervention outcomes for patients. Currently, researchers are in the first stages of identifying an Alzheimer 's-based blood test that could detect the disease before patients experience any symptoms, but concrete results are still to be published.¹¹ Dementia research will continue to advance to find a suitable therapeutic strategy that can be widely used to tackle this debilitating disease.