Plasma biomarkers in neuropsychiatric syndromes: A narrative review

Neuropsychiatric symptoms (NPS) are common features of neurodegenerative disease (NDD) but are relatively understudied compared to cognition, especially regarding biomarkers. Further, emerging evidence describes the utility of systematic assessment of NPS across the cognitive continuum, even in advance of dementia. In this narrative review, we discuss the role of plasma biomarkers in relation to NPS across the cognitive continuum of unimpaired, subjective cognitive decline, mild cognitive impairment, and dementia. While Alzheimer's disease is the primary focus, vascular, Lewy body, and frontotemporal dementia etiologies are also discussed. Literature searches included NPS and dementia-related search terms with additional literature identified based on the author group's subject area expertise. We found that plasma biomarkers are a burgeoning field, and scalability and accessibility make them well-suited for the study of NPS across the disease continuum. In early-stage NDD, diagnostic biomarkers are best suited for discriminating NDD-related NPS from non-NDD psychiatric syndromes and/or NPS due to other causes. In those with dementia, monitoring and prognostic biomarkers may enable the assessment of treatment response or help predict the risk of worsening symptoms. We conclude that plasma amyloid-β and tau show great promise in assessing NPS, especially during early-stage disease, but inflammatory and genetic biomarkers may also play a role across the disease course. Systematic research is required, keeping in mind the ethical considerations of knowing biomarker status in early-stage disease.