TY - JOUR EP - 1073 N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. KW - Alzheimer?s disease KW - amyloid KW - biomarkers KW - cerebrospinal fluid KW - cognition KW - neuropsychiatric symptoms KW - p-tau AV - public ID - discovery10205092 VL - 100 PB - IOS Press IS - 3 JF - Journal of Alzheimer's Disease UR - https://doi.org/10.3233/jad-240125 Y1 - 2024/07// A1 - Frank, Brandon A1 - Walsh, Michael A1 - Hurley, Landon A1 - Groh, Jenna A1 - Blennow, Kaj A1 - Zetterberg, Henrik A1 - Tripodis, Yorghos A1 - Budson, Andrew E A1 - O'Connor, Maureen K A1 - Martin, Brett A1 - Weller, Jason A1 - McKee, Ann A1 - Qiu, Wendy A1 - Stein, Thor D A1 - Stern, Robert A A1 - Mez, Jesse A1 - Henson, Rachel A1 - Long, Justin A1 - Aschenbrenner, Andrew J A1 - Babulal, Ganesh M A1 - Morris, John C A1 - Schindler, Suzanne A1 - Alosco, Michael L N2 - BACKGROUND: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear. OBJECTIVE: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (A?1-42, p-tau181), cognitive function, and NPS. METHODS: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOE?4. RESULTS: The sample was older adults (M?=?73.85, SD?=?6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n?=?688, 88.1%). Higher p-tau181/A?1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/A?1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/A?1-42 ratio was no longer associated with the NPI-Q. CONCLUSIONS: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia. SP - 1055 TI - Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms ER -