The Markers in Neuropsychiatric Disorders (MiND) Study

​Patients with younger onset dementia often endure a "diagnostic odyssey", seeing an average of three to five specialists before they receive a diagnosis.

A new study led by Professor Dennis Velakoulis (Department of Psychiatry) aims to help psychiatrists, neurologists and GPs in distinguishing distinguishing primary psychiatric disorders from neurodegenerative dementias, especially in younger patients.

The five-year longitudinal study Markers in Neuropsychiatric Disorders (MiND) will explore the diagnostic, health economic and broader utility of the biomarker of neuronal injury, neurofilament light (NfL) in the assessment of cognitive, neurological and psychiatric symptoms.

Dennis, who is Director of Neuropsychiatry at the Royal Melbourne Hospital and Clinical Director of the Melbourne Neuropsychiatry Centre (NorthWestern Mental Health and the University of Melbourne), says he hopes to alleviate the stress for patients.

“Patients come to our service anywhere between three to five years after seeing an average of five specialists, not including their general practitioner. This poses significant emotional stress and distress for patients and their families as well as substantial financial burden associated with travel for medical appointments and repeated, costly (and often invasive) investigations”, says Professor Velakoulis.

The five-year longitudinal study is funded by MACH, MRFF and NHMRC Ideas grants.

Dementia is caused by a heterogenous range of conditions such as Alzheimer disease and frontotemporal dementia. Younger onset dementia is defined as a dementia with symptom onset before 65 years of age. Younger patients typically present to general practice and specialist services with a constellation of psychiatric, cognitive, neurological, behavioural and personality changes. They often have complex, often ‘less typical’ presenting features than people with later onset dementia. This all contributes to a longer ‘diagnostic odyssey’ for patients –  many years of diagnostic uncertainty, misdiagnosis, imprecise care, and negative outcomes for patients and families.

Despite gold-standard multidisciplinary assessments and multimodal investigations, such as those routinely provided by the Melbourne Younger Onset Dementia service at Neuropsychiatry, RMH, up to 20 per cent of patients remain undiagnosed, with clinicians needing to adopt a suboptimal ‘watch and wait’ approach. In addition, with follow-up assessments, some patients have a change of diagnosis from neurodegenerative disorder to a different type, or to a psychiatric disorder.  This will have significant implications for ongoing care and management.

There is accumulating evidence of NfL as a biomarker for diagnosis, prognosis and treatment response in a wide range of neurological and neurodegenerative disorders. An innovative pilot study by the team demonstrated clinically important findings that NfL levels in cerebrospinal fluid (CSF) can distinguish psychiatric from neurodegenerative disorders with high accuracy, a finding with important clinical implications. (Eratne et al, 2020; https://doi.org/10.1177/0004867419857811).

The MiND Study expands on these findings by exploring NfL in blood in a broad range of diseases and settings, including primary care. The study aims to assess whether NfL could be used as a screening test, akin to a “C-reactive protein for the brain”, that can be used in specialist settings and general practice to inform precision care, diagnostic decisions and help guide specialist referral. Our preliminary plasma NfL results have been consistent with our initial CSF data.

“It is exciting to know that the results of this study could have clinically translatable outcomes for the assessment, care and management of people with neuropsychiatric and cognitive symptoms, significantly reducing their diagnostic odyssey and improving outcomes for them, their families, clinicians and the healthcare system”, says Dr Dhamidhu Eratne, a chief investigator and principal study clinician on the MiND Study.

The MiND Study has a target of 500 patients, with recruitment starting in early 2021 across Neuropsychiatry, general practice, memory clinics, as well as private clinics and health services in Victoria.

The study team have partnered with national and international leaders, including working closely with the Department of General Practice at the University of Melbourne, the Walter and Eliza Hall Institute of Medical Research, The Florey Institute of Neuroscience & Mental Health, Wicking Dementia Research & Education Centre, and The University of Gothenburg and Lund University in Sweden.

If you’re interested in learning more, or would like to collaborate, please contact the team at: www.themindstudy.org