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  -