Inconclusive research may end up benefitting people with dementia
Fifty million people worldwide suffer from the devastating effects of dementia on memory and behaviour. Alzheimer’s and vascular dementia are the two most common types; although the symptoms are similar, the treatment differs. Researchers tried to develop a new tool to distinguish these two types of dementia. The results were disappointing. Now it turns out that this is probably because many people have both types, so what looked like a failure may prove to be a breakthrough in treating people with dementia.
Dementia is rarely an isolated disease. People whose brain is incapacitated by dementia often have numerous comorbidities – but studies do not agree on which ones are more or less prevalent among people with dementia. Researchers therefore searched Denmark’s health registries to see whether the comorbid diseases among people with different types of dementia differ. The goal was to determine whether the type of dementia is associated with comorbidity.
“Since the different types of dementia require very different treatment, we hoped that the comorbidities might be able to distinguish between types of dementia. However, this only succeeded for people who developed dementia at an early age. When we examined this more closely, we found that the reason we did not find a difference could be that many people have multiple types of dementia, so they should actually be treated for these multiple types simultaneously,” explains Søren Brunak, Professor and Group Leader, Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.
Only found what was already known
The diagnostic process to evaluate the underlying cause of dementia can be challenging and inefficient, posing difficulty in differentiating between Alzheimer’s disease and vascular dementia, which was the original purpose of the project. About 60% of people with dementia have Alzheimer’s disease, characterized by an abnormal accumulation of amyloid beta protein, resulting in senile plaques that can disrupt signals between neurons and cause inflammation. In contrast, vascular dementia, which affects 20% of the people with dementia, is caused by reduced blood supply to the brain due to deteriorating blood vessels.
“Although the symptoms are similar, the causes and treatment differ widely, but doctors are often unsure of the correct diagnosis. We hoped by collecting data from a large number of patients that we could distinguish between the two types by statistically assessing the other diseases people with dementia have,” explains Isabella Friis Jørgensen, Postdoctoral Fellow, Novo Nordisk Foundation Center for Protein Research.
The researchers collected and compared data from 1994 to 2016 from Denmark’s health registries on the hospital encounters of more than 73,000 people with dementia to determine whether dementia is associated with the presence of other diseases. Unfortunately, the results were disappointing.
“Overall, we only got results we already knew. Our analysis could only identify a link to comorbidities for people with early onset dementia such as Down syndrome, alcohol-related diagnoses and cardiovascular disease that we already know are risk factors,” says Isabella Friis Jørgensen.
When the researchers examined the literature further, however, they were surprised but found a really good explanation for the frustrating results: mixed dementia.
“We had initially eliminated the people who had shown signs of both types of dementia from our analysis, but as we read through the literature based on brain scans and autopsies of patients, we realized that mixed dementia is far more common,” says Isabella Friis Jørgensen.
Whether one type of dementia leads to another is not known, but the researchers found that one comorbid condition of Alzheimer’s dementia turns out to be vascular dementia – and vice versa.
“New studies will naturally be needed to substantiate this result, and we are already well underway with these, but the more we analyse the data, the more convinced we become, especially because it all just suddenly makes really good sense,” explains Søren Brunak, and continues “Mixed etiologies – different mechanisms leading to highly similar outcomes – is a general problem in diagnosing diseases, in which several routes can lead to the same condition. Unravelling these mixtures is the primary goal of precision medicine”.
In addition to the challenge of making the right diagnosis, one major challenge of treating people with dementia has also been the difficulties in creating effective treatment.
“If you give a person with mixed dementia medicine for Alzheimer’s, it may well be effective against Alzheimer’s, but if they also have vascular dementia, they still show symptoms of dementia, which incorrectly indicates that the medication is not effective,” says Søren Brunak.
The researchers hope that they can return to the original study once everyone with mixed dementia is identified.
“Maybe we will find some comorbidity patterns among people with only one type of dementia. We cannot see the patterns now, but if our theory is valid, this may be serendipitous, so that we can both improve diagnosis and optimize the treatment of people with dementia,” concludes Søren Brunak.
“Age‐stratified longitudinal study of Alzheimer’s and vascular dementia patients” has been published in Alzheimer’s & Dementia. The authors are employed at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.