Neuropsychiatric symptoms in Alzheimer's continuum and their association with plasma biomarkers

Little is known about association between neuropsychiatric symptoms and plasma biomarkers across the entire Alzheimer's continuum.A total of 305 individuals with amyloid-β (Aβ) deposition (determined by 18F-florbetapir PET) participated in this study, including cognitively normal controls (n = 53), subjective cognitive decline (SCD, n = 75), mild cognitive impairment (MCI, n = 74), and dementia (n = 103). Plasma biomarkers (Aβ1-42, Aβ1-40, total tau [t-tau], phosphorylated tau 181 [p-tau181], and neurofilament light [NfL]), apolipoprotein E (APOE) genotyping and Neuropsychiatric Inventory Questionnaire (NPI-Q) were completed. Neuropsychiatric symptoms were classified into four subsymdromes (hyperactivity, psychosis, affective, and apathy). Logistic regression analysis was conducted to investigate relationships between neuropsychiatric symptoms and plasma biomarkers.About one-third of cognitively unimpaired individuals (normal controls: 34.0 %, SCD: 28.0 %) reported one or more neuropsychiatric symptoms, and more in symptomatic stages such as MCI (40.5 %) and dementia (81.0 %). Plasma NfL significantly increased in dementia group compared to SCD and healthy controls, relating to a higher risk of aberrant motor behavior, anxiety, sleep disturbance, disinhibition, and euphoria. Older age (odds ratio [OR] = 1.079, 95 % confidence interval [CI] = 1.022-1.140, p = 0.006), lower cognitive score (OR = 0.846, 95%CI = 0.791-0.905, p < 0.001) and increased plasma NfL (OR = 1.021, 95%CI = 1.00-1.042, p = 0.041) could predict psychosis. No significant differences were found in plasma Aβ1-42/Aβ1-40, t-tau or p-tau181 across all groups, and none correlated with neuropsychiatric symptoms.The cross-sectional design, small sample size and use of NPI-Q.This study supported neuropsychiatric symptoms as early manifestations of preclinical Alzheimer's disease, and suggested plasma NfL to be a potential biomarker for detecting neuropsychiatric symptoms in Alzheimer's continuum.