‘Clear correlation’ found between atrial fibrillation and risk of vascular dementia

6th June 2024

A new study has demonstrated a ‘clear correlation’ between atrial fibrillation and vascular dementia, as well as a much higher risk of developing stroke or a major blood clot than those without the heart condition.

Researchers at the University of Birmingham found that individuals with atrial fibrillation, who were considered low-risk patients, had a 68% higher chance of developing vascular dementia than patients without the heart condition. There was however no correlation with the development of Alzheimer’s disease.

The research also found that the low-risk patients had double the chance of developing a stroke or major blood clot than those without atrial fibrillation and suggest that a thromboembolic mechanism is contributing to the development of vascular dementia in patients with atrial fibrillation.

This adds to existing evidence that the heart condition is associated with strokes and blood clots in older patients and those with other health conditions.

The findings, published in the journal Nature Medicine, highlight an additional consequence of this common heart condition, which the researchers advise clinicians to be aware of and attempt to prevent, particularly amongst younger, lower risk patients.

Patients with atrial fibrillation are typically given anticoagulants as stroke prevention therapy but younger patients and those otherwise perceived as ‘low-risk’ are not prescribed the blood thinning medication.

The study was a UK population-based analysis using electronic healthcare records from 5,199,994 primary care patients collected between 2005 and 2020. Just over 5% (290,525) of the patients analysed, who were all between the ages of 40 and 75, had a diagnosis of atrial fibrillation.

The researchers focused on 36,340 of these patients who were not receiving anticoagulation therapy and were considered low-risk based on a standard risk score (CHA₂DS₂-VASc score <2). The team compared these patients’ outcomes with those of 117,298 control patients without atrial fibrillation, who were matched for age, sex and region.

Rates of death and thromboembolic outcomes, including vascular dementia, during the study were substantially increased in the patients with atrial fibrillation despite their low-risk status.

In the five-year follow up period, 3.8% of patients with atrial fibrillation had a stroke compared with 1.5% of those without the heart condition. Meanwhile, 5.6% versus 2.7% developed ischaemic heart disease, respectively. All-cause mortality was also increased in those with atrial fibrillation, at 8.9% versus 5% for those without.

Adjusting for various potential contributing factors, the authors found atrial fibrillation was associated with a two-fold increased risk of stroke and 1.9-fold increased risk of ischaemic heart disease.

Atrial fibrillation was also associated with an increased rate of all-cause dementia (1.2% versus 0.7% in those without). The report this was driven by vascular dementia cases (0.4% versus 0.1%, respectively), and that those with atrial fibrillation had a 1.68-fold increased risk of developing vascular dementia compared to those without after adjusting for other factors.

Alastair Mobley, a PhD researcher at the University of Birmingham and first author of the study, said: ‘This study demonstrates a clear correlation between AF and vascular dementia. This may have a similar mechanism to the association between AF and stroke.’

The prevention of thromboembolism in atrial fibrillation is typically restricted to older patients or those with specific risk factors and currently does not consider outcomes such as vascular dementia. Ongoing clinical trials such as DaRe2THINK are exploring whether anticoagulants in lower-risk patients can provide a way to prevent the increased risk of thromboembolic outcomes, including vascular dementia.

Dipak Kotecha, professor of cardiology at the University of Birmingham and senior author of the study, added: ‘Atrial fibrillation is one of the most common heart conditions. With its prevalence continuing to rise, it is crucial that we develop strategies to prevent not only stroke but outcomes like dementia, which are a big concern for patients and healthcare systems. Our research highlights the urgency of addressing AF comprehensively, considering its overall impact on the wellbeing of patients.’

A version of this article was originally published by our sister publication Nursing in Practice.

Potential treatment route for vascular dementia uncovered by UK researchers

14th August 2023

A potential therapeutic target underlying the cause of reduced cerebral blood flow to the brain that results in vascular dementia has been recently discovered by researchers at the University of Manchester.

Published in the journal Proceedings of the National Academy of Sciences, the study, which was carried out in mice, reveals that hypertension disrupts signalling within artery cells in the brain and leads to vascular dementia. To date, there is limited understanding of the cellular and molecular mechanisms by which elevated blood pressures give rise to changes in brain arteries.

The researchers used a blood pressure high (BPH/2) mouse model of hypertension. They studied pial arteries, which regulate the flow of blood across the brain surface through myogenic constriction.

Normally, vasodilatation within these arteries occurs through activation of large-conductance, calcium-activated potassium channels on the plasma membrane by nearby localised calcium-release events – referred to calcium sparks – from the sarcoplasmic reticulum (SR) of vascular smooth muscle cells.

In contrast, vasoconstriction occurs as a result of diminished activity of the calcium-activated potassium channels.

Vascular dementia in a mouse model

The researchers found that in the hypertensive mice, there was increased constriction of pial arteries, which suggested that the calcium sparks occurred normally. However, they also observed that the distance between the SR and the potassium channels was increased. Consequently, the calcium sparks failed to activate the potassium channels, preventing the normal vasodilatory response.

The net effect was increased constriction of arteries, reducing cerebral blood flow and behavioural alterations in the mice that approximated to deficits observed in human vascular dementia patients, including executive dysfunction, apathy and memory loss.

Professor Adam Greenstein, a clinician scientist specialising in high blood pressure at the University of Manchester and one of the leaders of the research, said: ‘By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks. 

‘Any drugs that are discovered to improve brain blood supply may also be able to open a new line of attack in treating Alzheimer’s disease, which causes very similar damage to blood vessels as vascular dementia. Drugs to restore healthy blood flow could make current treatments, which focus on removing harmful amyloid plaques in the brain, more effective.‘

Professor Sir Nilesh Samani, medical director at the British Heart Foundation, which funded the research, added: ‘Vascular dementia affects around 150,000 people in the UK, and this number is going up. There are no treatments to slow or stop the disease, but we know that high blood pressure is an important risk factor. The incurable symptoms are hugely distressing for patients and those close to them.   

‘This exciting research reveals a specific mechanism by which high blood pressure might increase the risk of vascular dementia. Pinpointing how arteries remain permanently narrowed in vascular dementia could lead to the development of new effective treatments, raising hope that there may soon be a way to prevent this illness from destroying more lives.‘