Abstract
BackgroundLittle is known about association between neuropsychiatric symptoms and plasma biomarkers across the entire Alzheimer's continuum. MethodsA 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. ResultsAbout 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. LimitationsThe cross-sectional design, small sample size and use of NPI-Q. ConclusionsThis 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.
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