The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum

•To relate Alzheimer's disease (AD) biomarkers with neuropsychiatric symptoms.•AD biomarkers were related to the presence of anxiety and apathy, but not with depression, agitation, irritability, and sleep. The associations with anxiety and apathy were mediated by MMSE score.•AD pathology has an effect on anxiety and apathy due to disease severity. To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. Data from two large cohort studies, the Dutch Parelsnoer Institute – Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aβ42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aβ42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aβ42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.