Dynamics between Neuropsychiatric Symptoms and Biomarkers: A Pilot Study

Abstract

AbstractBackgroundThe aetiology of neuropsychiatric symptoms (NPS) in dementia remains unclear, and currently, it is challenging to distinguish neuropsychiatric manifestations related to younger‐onset neurodegenerative diseases from those of primary psychiatric disorders. Neurofilament light chain (NfL) is a promising biomarker for axonal injury and has been found to differentiate between neurodegenerative diseases and primary psychiatric disorders. The aim was to investigate cerebrospinal fluid (CSF) NfL and its relationship with NPS and compare it with traditional biomarkers, namely Aβ and tau.MethodsRetrospective data for 54 patients with younger‐onset dementia was collated (mean age ± SD, 57.9 ± 7.1, females n = 15 [28%], co‐morbid psychiatric diagnoses n = 17 [31%]). Of these, 23 had Alzheimer’s disease (AD), 14 had frontotemporal dementia (FTD), 9 had mild cognitive impairment (MCI), and 8 were diagnosed with other types of dementia. Neuropsychiatric measures were extracted from the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), the Depression Anxiety and Stress Scale 21 (DASS‐21), and the revised Cambridge Behavioural Inventory (CBI‐R). CSF biomarkers included NfL, Ab‐42, p‐tau and t‐tau.ResultsNo significant associations between NPS and NfL was seen in patients with AD, FTD, MCI or other diagnoses. In the combined cohort, a positive correlation was found between the overall cognitive functioning and Ab‐42 levels (r = 0.47, p = 0.01), and visuoconstruction, a specific domain of cognitive functioning, was found to be positively correlated with Ab‐42 levels (r = 0.44, p = 0.03) and negatively correlated with t‐tau levels (r = ‐0.43, p = 0.03). In FTD, a positive correlation was found between stress and p‐tau levels (n = 8, r = 0.89, p = 0.04), and this correlation was stronger in patients without co‐morbid psychiatric diagnoses (n = 7, r = 0.93, p = 0.03).ConclusionThe results suggest that levels of CSF biomarkers, especially Ab‐42, are linked to deficits in cognitive functioning in patients with younger‐onset dementia, and levels of p‐tau are strongly related to stress particularly in the absence of co‐morbid psychiatric diagnoses. Therefore, these biomarkers may assist in the identification of patients who are at an increased risk of developing cognitive impairment and stress.