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Could a routine blood test improve dementia outcomes, and transform care for people with symptoms and illnesses of the mind and brain?
By Stefanie Colella, Stakeholder Engagement and Communication Manager, Neuropsychiatry at the Royal Mebourne Hospital, and the Primary Times Editorial Team
Source: APNA Primary Times Summer 2021 (Volume 21, Issue 2)
Timely and accurate diagnosis of dementia can be challenging. Many people face years of multiple assessments, repeated and costly investigations, misdiagnosis, uncertainty, frustration, and stress. All this is associated with significant negative outcomes for them, their families, their clinicians, and health care systems. Significant proportions of people are initially (mis)diagnosed with a primary psychiatric illness. These challenges are greater for people with younger-onset dementia (YOD; onset of symptoms before age 65 years), where ‘atypical’ presentations are more common and where dementia is less likely to be suspected.
Currently, there are an estimated 28,300 Australians living with YOD, and that number is projected to increase to 41,250 by 2058.1 Dementia is the second leading cause of death in Australia.2 There is still a great need for simple, widely available blood tests to improve assessment and care for people with cognitive, neurological, and psychiatric symptoms.
To help improve early and accurate diagnosis and outcomes, a team of researchers from Neuropsychiatry at the Royal Melbourne Hospital (RMH) are exploring blood biomarkers for people with cognitive, psychiatric and neurological symptoms through the Markers in Neuropsychiatric Disorders (MiND) Study.
Dr Dhamidhu Eratne, the study’s chief investigator and a consultant neuropsychiatrist at the RMH, told Primary Times, ‘The goal of the research is to lead to a routine, widely available simple blood test to help GPs and other medical specialists. [The tests would] reduce the delay to diagnosis of dementia and other neurological and neurodegenerative disorders,’ he says, ‘and improve outcomes for people with cognitive, psychiatric and/or neurological symptoms, their families, clinicians and health-care systems.’
Early findings from the MiND Study show that levels of the braincell protein neurofilament light (NfL), a marker of nerve cell injury, can indicate whether someone has dementia, or not.3,4,5 These groundbreaking studies have demonstrated high accuracy in distinguishing neurodegenerative disorders and dementia from non-neurodegenerative and primary psychiatric disorders (e.g., Alzheimer’s disease from depression/‘pseudodementia’, and frontotemporal dementia from bipolar disorder), which is a common and challenging diagnostic dilemma in clinical practice.3
‘NfL levels have been found to be significantly elevated in people with neurodegenerative disorders compared to primary psychiatric and non-dementia disorders,’ Dr Eratne says. ‘These elevated NfL levels distinguish neurodegenerative from primary psychiatric causes of cognitive, neurological and psychiatric/behavioural symptoms, with very high accuracy (more than 90%), thus showing great promise for a simple screening blood test to reduce diagnostic delay, reduce misdiagnosis, and improve precision care and outcomes.’
According to Professor Dennis Velakoulis, Director of Neuropsychiatry, RMH, and MiND Study lead investigator, ‘These findings are significant, given that timely and accurate diagnosis of younger-onset dementia and other neurodegenerative disorders, particularly in the early stages, can be challenging in clinical practice. In many situations, the blood tests, the brain scans, even the memory testing, can be close to normal. GPs and other specialists too often experience uncertainty if someone has mental health or psychiatric symptoms or a disorder, like depression.’
Professor Velakoulis says, ‘In many neurological disorders, particularly in dementia, there are brain cells that are dying and releasing NfL … so when we see elevated levels in the spinal fluid or blood, it indicates that there has been some brain cell injury. People with psychiatric illnesses, or people who are healthy, don’t have brain cells dying like this, so we see low, normal levels of NfL.’
The MiND Study team is aiming to lead to a simple blood test widely available to GPs across the country and is currently working with the Integrated Mental Health Team at the Department of General Practice at the University of Melbourne, headed by Professor Jane Gunn.
Dr Eratne says some additional objectives of the study are to build strong relationships with general practice by setting up a platform to support cross-disciplinary collaboration and opportunities for broad biomarker and clinical, cognitive and psychosocial research.
‘The study is aiming for clinical translation by demonstrating the diagnostic, clinical and health economic utility of a blood test for NfL,’ he says. ‘We need help from GPs and practice nurses with referring eligible patients, so we can understand how this test performs in a primary-care setting, its feasibility, and how this could be implemented in primary care, to help GPs and their patients in the future. We have very broad eligibility criteria – patients who present with recent (within 5 years) history of cognitive, psychiatric, and/or neurological symptoms, and, healthy controls aged 18 years and over.’
The MiND Study is recruiting participants from all over Victoria, and has now expanded to QLD, WA, with NSW and SA soon to follow. There are a range of other sub-studies, and full information and the short online referral form are available via https://themindstudy.org/refer.
Acknowledging the numerous existing commitments of general practice teams, Dr Eratne says requirements for GPs are kept as simple as possible, with the minimum requirement being completion of a brief, 2-minute online referral form. The study team will do the rest, including contacting, recruiting and organising blood sample collection at a local Melbourne pathology or Sonic Pathology collection centre.
But, of course, any GPs or practices that would like to be more involved, would be warmly welcomed. ‘The first step is recruiting participants and getting the data,’ Dr Eratne says. ‘Regarding the next step of actual implementation, we see this as being available as a routine diagnostic screening test, akin to a ‘C-reactive protein or prostate-specific antigen for the brain’, to quickly tell if ‘something neurological is going on’ for people with cognitive, neurological and/or psychiatric symptoms. This would be similar to testing full blood count and thyroid function as part of standard dementia screening blood tests.’
Another aim of the MiND Study is simple blood tests to support general practices in preventative health and early intervention approaches, given biomarkers often start changing in a range of illnesses, years before the onset of clinical symptoms.
‘We anticipate that one day in the future, NfL could even be a test that could be done periodically, similar to cardiovascular risk-factor monitoring, such as lipid monitoring,’ Dr Eratne says. ‘[This could be] a way of predicting future risk and therefore intervening prior to the onset of clinical symptoms (when lifestyle and other interventions are more likely to be more effective) and preventing the development of illness/clinical symptoms.’
1. Dementia Australia, ‘Dementia in Australia: prevalence estimates 2018-2058’, September 2018, accessed 25 October 2021. https://www. dementia.org.au
2. Australian Bureau of Statistics, ‘Causes of death, Australia’, 29 September 2021, accessed 25 October 2021. https://www.abs. gov.au
3. D Eratne, SM Loi, N Walia et al., ‘A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: a ‘C-reactive protein’ for psychiatrists and neurologists?’, Aust N Z J Psychiatry, 2020, 54(1):57–67, doi:10.1177/0004867419857811.
4. D Eratne, S Janelidze, CB Malpas et al., ‘Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives’, Aust N Z J Psychiatry, 2021, in press.
5. D Eratne, SM Loi, QX Li et al., ‘Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive Alzheimer and frontotemporal disorders in clinical settings’, Alzheimers Dement, 2021, in press.