Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms

• DOI: 10.3233/jad-240125
• Publication Date: 2024-07-12T14:48:58Z
• Authors: Brandon Frank; Michael Walsh; Landon Hurley; Jenna Groh; Kaj Blennow; Henrik Zetterberg; Yorghos Tripodis; Andrew E. Budson; Maureen K. O’Connor; Brett Martin; Jason Weller; Ann McKee; Wendy Qiu; Thor D. Stein; Robert A. Stern; Jesse Mez; Rachel Henson; Justin Long; Andrew J. Aschenb...; Ganesh M. Babulal; John C. Morris; Suzanne Schindler; Michael L. Alosco
• Keywords: Clinical Dementia Rating; Montreal Cognitive Assessment; Apolipoprotein E

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer’s disease (AD). However, the associations among NPS, cognition, and AD biomarkers across spectrum are unclear. Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) (Aβ1-42, p-tau181), cognitive function, NPS. Methods: Primary models included 781 participants from National Coordinating Center (NACC) data set who had CSF for using Lumipulse. NPS were assessed with Inventory Questionnaire (NPI-Q). cognition harmonized MMSE/MoCA, as well neuropsychological tests sensitive to pathology: story recall, naming, animal fluency, Trails B. The Clinical Dementia Rating (CDR®) scale dementia severity. Mediation estimated Kemeny metric covariance in a structural equation model framework, controlling age, education, sex, APOE ɛ4. Results: sample was older adults (M = 73.85, SD 6.68; 49.9% male, 390; 27.9% dementia, 218) predominantly white (n 688, 88.1%). Higher p-tau181/Aβ1-42 ratio predicted higher NPI-Q, which partially mediated by MMSE/MoCA and, second model, recall. No other pathway statistically significant. Both NPI-Q independently association CDR global impairment. With excluded, no longer associated NPI-Q. Conclusions: may secondary impairment pathology through direct indirect pathways. predict severity AD. likely plays less role samples without dementia.