|Beitragstitel||Blood plasma protein profiles of neuropsychiatric symptoms and related cognitive decline in older people|
Neuropsychiatric symptoms (NPS) in older people worsen the patients’ and caregivers’ quality of life and are associated with cognitive decline. This study tested the hypothesis that altered protein levels in blood plasma are associated with NPS and these proteins improve prediction of NPS. Additionally, we explored the association of the protein patterns with AD pathology and tested whether these proteins predict persistent NPS and cognitive decline over time.
We performed a cross-sectional and longitudinal study in older people with and without cognitive impairment in a memory clinic setting. NPS were recorded through the Neuropsychiatric Inventory Questionnaire (NPI-Q) while cognition was assessed through a comprehensive neuropsychological test battery collected at baseline and follow-up visits. CSF biomarkers of AD pathology were assessed and used to determine the presence/absence of AD pathology. Shotgun proteomic analysis based on liquid chromatography-mass spectrometry identifying 420 proteins were conducted in blood plasma samples of all participants. Multivariate linear regression and correlation analysis were used.
Eighty-five subjects with a mean age of 70 (± 7.4) years, 62% female and 54% with mild cognitive impairment or mild dementia were divided into groups with (NPI-Q score > 0) and without NPS. We found 15 plasma proteins with altered baseline levels in participants with NPS. Adding the 15 altered proteins to a reference model based on clinical data (age, sex, years of educations, and clinical dementia rating sum of boxes score), significantly improved the prediction of NPS (from receiver operating characteristic area under the curve (AUC) 0.75 to AUC 0.91, p = 0.004) with a specificity of 89% and a sensitivity of 74%. These identified proteins additionally predicted both persisting NPS and cognitive decline at follow-up visits. The observed associations were independent of the presence of AD pathology.
Using a proteomic approach, we identified a panel of specific blood proteins associated with current and future NPS, and related cognitive decline in older people. These findings show the potential of untargeted proteomics to identify blood-based biomarkers of pathological alterations relevant for NPS and related clinical disease progression.