AT(N), neuronal and glial biomarkers in young‐onset neurodegenerative disorders and psychiatric disorders and their associations with neuropsychiatric symptoms and cognition

Abstract Background It is clinically a challenging task to accurately differentiate complex young‐onset neurodegenerative disorders from psychiatric disorders which often present with similar neuropsychiatric symptoms (NPS) in their early stages. The aim of this study is to provide a more nuanced understanding of the interplay between NPS, cognition and multiple pathologies that may drive these disorders. Method This study was conducted at the Neuropsychiatry Centre, the Royal Melbourne Hospital, Melbourne, Australia, as part of a large, multi‐site research study, the Markers in Neuropsychiatric Disorders Study. Sixty participants, including people with Alzheimer’s disease, Huntington’s disease, frontotemporal dementia, major depressive disorder and generalised anxiety disorder and together with healthy controls, were recruited and assessed for plasma biomarkers, NPS and cognition. Their plasma levels of amyloid‐beta, total‐tau (t‐tau), phosphorylated‐tau (p‐tau), neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) were measured. The severity of multiple common NPS such as depression, anxiety and apathy were also measured. Cognitive functions were measured by a combination of cognitive screening tool and standardised neuropsychological assessments. General linear regressions were used to investigate the associations between biomarkers, NPS and cognition in these disorders and the differences between the two clinical groups. Result The analysis of the collected data is ongoing. However, results from a pilot study suggest that memory recall was related to an interplay between AT(N) pathologies, and executive function was related to a neuronal pathology. The severity of NPS may moderate these relationships. Conclusion Young‐onset neuropsychiatric disorders, presenting with overlapping symptoms, pose a diagnostic dilemma. The results of this study provide a more nuanced understanding of the intricate interplay between NPS, cognition and biomarkers that may shed light into the differentiation between young‐onset neurodegenerative disorders and psychiatric disorders.