Getting a diagnosis of young-onset dementia can take a very long time, often three to five years, and sometimes longer. Early symptoms are often changes in mood, behaviour or personality. These look a lot like depression, bipolar disorder or schizophrenia. Some conditions, such as behavioural-variant frontotemporal dementia, are especially hard to tell apart. Many people are given a psychiatric diagnosis first and only find out the real cause years later. Those years are extremely hard on people and their families.
Measuring a protein in the blood called neurofilament light chain, or NfL, may help. NfL sits inside the nerve cells of the brain. When those cells are damaged, like in dementias, NfL leaks out into the fluid around the brain and into the blood, so levels go up. In psychiatric conditions, NfL levels usually stay in the normal range. NfL can help answer an important question: are these symptoms caused by something damaging brain cells, like a dementia, or not?
To investigate this question, our team at The Royal Melbourne Hospital runs The Markers in Neuropsychiatric Disorders Study (The MiND Study), one of the largest studies of its kind. More than 1,000 people have taken part, from right across Australia, including one in three who live outside a major city. In our recent work, NfL levels were around two and a half times higher in people with dementia than in people with a psychiatric condition and healthy people. A simple blood test was about as accurate as a spinal fluid test. It worked well at all ages, and it was especially accurate in younger people, which is exactly where diagnosis is hardest. We have also shown the test could have reduced misdiagnosis, and helped people reach the right answer sooner.
What can this mean in practice? A very high NfL level can quickly point to dementia as the cause of symptoms rather than a psychiatric condition. That prompts further assessment and can open the door to specific treatments and supports. A very low level can be reassuring against dementia, so the focus can shift to treating psychiatric symptoms and other medical issues that may be contributing, while still keeping watch over time.
These tests are available in Australia now, and a doctor can order them. If you or your family are still unsure about a diagnosis, and have symptoms, it is worth raising with your specialist team.
It is just as important to say what these tests are not currently for. They are not currently recommended for people who feel well and are worried about their risk of dementia in the future – we still need to do much more research first.
There is still a lot to work out. Different laboratories use different machines, and the normal ranges they compare your result against can differ. Levels are affected by your age, as well as things like weight, how well your kidneys are working, and other medical issues. And while NfL is very accurate for a single test, no test is perfect. It has to be read alongside your history, examination, scans and everything else your doctors know about you. That is why these tests belong in a conversation with your treating team, and are best used in specialist services for now. Research is underway, including by our group, to find out how well they work in general practice.
This is an exciting time. Our group and many groups around the world are working hard on these questions. The hope is that tests like these will not only give answers sooner, but help track brain health over time, so the right support and treatment can start earlier.
Soon I will write about a different blood test, phosphorylated tau 217 (p-tau217), a very promising test which looks specifically for Alzheimer’s disease.
You can read more about our work at themindstudy.org, and please don’t hesitate to get in touch with me via [email protected].
By Dr Dhamidhu Eratne
Consultant Neuropsychiatrist, Neuropsychiatry Centre, Royal Melbourne Hospital
Clinician-Researcher and Postdoctoral Research Fellow, University of Melbourne
