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Study identifies new treatment targets for vascular dementia

Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney

Key Facts:

• Vascular dementia is common, serious, and currently has no approved treatments
• It is caused by damage to blood vessels in the brain
• New research has identified potential biological targets to guide future studies
• Translating these findings into treatments will require substantial further research
• Genetics-led approaches may help uncover new pathways for future therapies

A new study led by researchers at UNSW Sydney’s Centre for Healthy Brain Ageing (CHeBA) has identified potential biological targets that could help guide future research into treatments for vascular dementia – a common and serious yet currently untreatable form of dementia.

Vascular dementia, caused by damage to blood vessels in the brain, is the second most common form of dementia worldwide, accounting for around 15–20% of all cases. Despite its prevalence and impact, there are currently no approved treatments in Australia for this condition.

Dr Matthew Lennon, lead author of the study published in Alzheimer's & Dementia: Translational Research & Clinical Interventions, a journal of the Alzheimer’s Association, says the findings represent an early but important step in a longer research journey.

“Vascular dementia is a major and growing public health problem. It affects memory, thinking, and function, yet we have no effective treatments to stop or slow its progression. Our study provides an initial step by identifying biologically plausible targets that could inform future research into therapies,” said Dr Lennon.

Using genetics to unlock new research directions

The research used a cutting-edge genetic approach known as Mendelian randomisation to analyse more than 12,000 potentially ‘druggable’ genes – which, along with the proteins they produce, could be targeted by medications. By examining large-scale genetic datasets from hundreds of thousands of individuals, the team identified genes that may play a causal role in vascular dementia.

The study identified four such genes linked to vascular dementia risk:

• APOE and TOMM40 – well-established genes already known to play roles in brain health and dementia
• ERAP and SAA1-4 – newer, emerging targets linked to inflammation and immune processes

Importantly, the two strongest signals, APOE and TOMM40, were also associated with brain imaging markers of small vessel disease, a major contributor to both vascular dementia and Alzheimer’s disease. This strengthens the evidence that these genes are involved in underlying disease processes.

A major unmet need

Unlike Alzheimer’s disease – where several treatments exist and many more are in development – vascular dementia research has lagged behind, leaving patients with limited options.

“Managing risk factors like blood pressure and cholesterol helps, but it’s not enough,” Dr Lennon said. “Even under ideal conditions, prevention strategies may only reduce dementia risk by less than half. We urgently need new avenues for research into targeted treatments.”

Cautious optimism for the future

The identification of these genes may help inform future work aimed at:

• Developing drugs that target pathways relevant to vascular dementia
• Exploring whether existing medications acting on these genes could be repurposed
• Improving understanding of how vascular and Alzheimer’s disease processes overlap

However, the researchers emphasise that translating genetic findings into safe and effective treatments is a complex and lengthy process, and many potential drug targets do not ultimately lead to successful therapies.

Professor Perminder Sachdev, Co-Director of CHeBA, said the findings highlight the value of this approach.

“At a time when vascular dementia remains a major unmet medical need, this study highlights the potential of genetics-led research to uncover new treatment pathways and bring hope for future therapies.”

While further work is needed – including laboratory studies, additional genetic analyses and clinical trials – the study provides an important lead for future drug development.

“This is an important first step,” Dr Lennon said. “By identifying potential targets, we can begin to better understand where future research and drug development efforts might be directed.”

About the study

The research was conducted by scientists at UNSW Sydney’s Centre for Healthy Brain Ageing (CHeBA) and funded by the Dementia Australia Research Foundation (DARF) Royce Simmons Project Grant.

 

Contact details:

Dr Matthew Lennon
Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney
Email: [email protected]