Association of Apathy with Amyloid‐β and Tau in Cognitively Unimpaired Older Adults: Findings from the Harvard Aging Brain Study

Abstract

AbstractBackgroundApathy is one the most common neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) and is associated with elevated AD pathology in cognitively impaired individuals. However, it remains unclear if apathy is associated with AD pathology, specifically amyloid‐β and tau, in cognitively unimpaired (CU) older adults. Therefore, we examined cross‐sectional relationships between apathy and neuroimaging AD biomarkers in CU older adults from the Harvard Aging Brain Study (HABS).MethodHABS is a prospective cohort study that enrolled CU older adults. A random subset of HABS participants (n = 142, age: 80.53 ±6.0, 57% female) and their study partners (SP) completed the Apathy Evaluation Scale‐Self (AES‐S) and ‐Informant (AES‐I). The AES consists of 18 items rated on a 4‐point Likert‐type scale; lower scores indicate greater apathy. We used Pittsburgh Compound B (PiB) PET cortical composite distribution volume ratio to measure amyloid‐β (Aβ), and flortaucipir (FTP) PET standardized uptake value ratio in two regions (bilateral entorhinal (ER) cortex and inferior temporal (IT) cortex) to capture regional tau. We assessed the association of AES‐S or AES‐I (dependent variable) with Aβ, or each of the two regional tau values (independent variable), in linear models adjusting for age, sex, and education. We then explored Aβ‐independent associations between regional tau and AES‐I/AES‐S, by additionally adjusting for Aβ in each tau model.ResultElevated Aβ (β = ‐3.7, p = 0.015) and ER Tau (β = ‐6.0, p = 0.016) were associated with lower AES‐I, while IT tau was not (p = 0.14). None of the AD pathology measures were associated with AES‐S (all; p>0.23). ER tau was no longer associated with AES‐I once Aβ was also adjusted for in the model (β = ‐4.4, p = 0.100).ConclusionGreater Aβ and tau levels were associated with higher apathy in CU older adults. Our findings imply that even in CU older adults, apathy is closely related to AD pathology may be more accurately measured by study partner report than self‐report, which may reflect a measurement property of this NPS. Further study of apathy in preclinical stages is needed to provide understanding of potential interventions to prevent or delay behavioral symptoms of AD.