Cross‐Sectional and Longitudinal Associations of Mild Behavioural Impairment‐Apathy and Alzheimer’s Disease‐Related Biomarkers

Abstract

AbstractBackgroundApathy, characterized by decreased interest, initiative, and emotional reactivity, is amongst the most common neuropsychiatric symptoms in Alzheimer’s Disease (AD) dementia, but it can also manifest in prodromal, and even preclinical disease stages. Apathy in individuals who are cognitively normal and who have mild cognitive impairment (MCI), is associated with accelerated progression to AD, and apathy in AD has been associated with greater disability, lower quality of life, poorer health, greater caregiver distress and burden, as well as higher morbidity and mortality. The multitude of negative outcomes associated with apathy highlight the importance of research whose primary goal is to identify mild behavioural impairment(MBI)‐apathy in non‐dementia samples and combine this behavioural syndrome with well‐established AD‐biomarkers, such as beta‐amyloid (Aβ), phosphorylated tau (p‐tau), and total tau (t‐tau), to better predict AD dementia risk.MethodDementia‐free participants in the Alzheimer’s Disease Neuroimaging Initiative were stratified as MBI‐apathy and no neuropsychiatric symptoms (no‐NPS) based on Neuropsychiatric Inventory (NPI) and NPI‐Questionnaire (NPI‐Q) scores at two consecutive visits. Covariates of interest included age, sex, apolipoprotein ε4 carriership, years of education, Mini Mental State Examination scores, and the questionnaire NPS status was derived from. Linear regressions assessed the association of MBI‐apathy (predictor) with Aβ40, Aβ42, p‐tau181, t‐tau, Aβ40/Aβ42, p‐tau181/Aβ42, and t‐tau/Aβ42 (outcome variables). We also used linear mixed effect models for repeated measures to investigate change in our outcome variables across a two‐year period.ResultsOf the 253 participants (127 CN); 51 had MBI‐apathy. MBI‐apathy was found to be significantly associated with baseline p‐tau181/Aβ42 (p<0.05) and t‐tau/Aβ42 (p<0.05) ratios. MBI‐apathy was also found to be significantly associated with changes in Aβ42 (p = 0.001), Aβ40/Aβ42 (p<0.01), p‐tau181/Aβ42 (p = 0.001), and t‐tau/Aβ42 (p = 0.001) levels and ratios over a two‐year period.ConclusionTo our knowledge, this is the first study examining the relationship between MBI‐apathy and AD‐related biomarkers. Results suggest that MBI‐apathy is significantly associated with several AD‐related biomarkers both cross‐sectionally and longitudinally. Combining the presence of persistent and emergent apathy with these biomarkers might serve as a prognostically useful approach for predicting AD dementia at a time when there is opportunity for intervention.