Mild Behavioural Impairment-Apathy and Alzheimer's Disease Plasma Phosphorylated Tau Biomarker Levels

BackgroundMild behavioural impairment (MBI), characterized by later-life emergence of persistent neuropsychiatric symptoms (NPS), is an early clinical indicator of dementia risk. MBI as a global construct has been associated with Alzheimer disease (AD) pathology; studies have also explored MBI domains. Prior work has linked MBI-apathy to cerebrospinal fluid (CSF) biomarkers of AD, but whether similar associations are detectable using plasma-based biomarkers such as phosphorylated tau (p-tau) is unknown. Establishing such relationships is critical, as plasma biomarkers are more accessible than CSF. ObjectiveTo explore cross-sectional and longitudinal associations between MBI-apathy and plasma p-tau181 using Alzheimers Disease Neuroimaging Initiative data. MethodsOlder adults with normal cognition or mild cognitive impairment were categorized as MBI-apathy (n=69), non-MBI NPS (n=112), and no-NPS (n=215) based on Neuropsychiatric Inventory scores and symptom persistence over one year. Linear regression modelled cross-sectional associations between NPS group and plasma p-tau181 levels, adjusting for age, sex, education, apolipoprotein E4 status, and Mini-Mental State Examination score. Hierarchical linear mixed-effects modelling assessed associations over two and three years, including time-by-NPS group interactions. ResultsMBI-apathy was associated with significantly higher plasma p-tau181 levels at baseline (24.05% [6.06-45.08%]; adjusted p=0.014), and over two (26.46% [7.24-49.12%]; adjusted p=0.012) and three years (29.28% [10.17-51.72%]; adjusted p=0.004) compared to no-NPS. No significant associations were observed for non-MBI NPS. ConclusionsMBI-apathy is associated with elevated plasma p-tau181 cross-sectionally and longitudinally. These findings support MBI-apathy as a potential proxy marker of tau pathology for early AD detection.