Neuropsychiatric symptoms in cognitive decline and Alzheimer's disease: biomarker discovery using plasma proteomics

Background and objectives Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression. Methods A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer's Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest. Results A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p