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Abstract Details

Association Between Cerebrospinal Fluid Biomarkers of Amyloid and Tau and Neuropsychiatric Symptoms Among Participants from the National Alzheimer’s Coordinating Center Uniform Data Set
Aging, Dementia, Cognitive, and Behavioral Neurology
P10 - Poster Session 10 (8:00 AM-9:00 AM)
7-004
Neuropsychiatric symptoms are often an early manifestation of AD. Previous research using CSF Aβ and p-tau suggests the effects of AD pathology on NPS are mediated by cognitive impairment. The causes of NPS across the disease continuum are poorly understood.
To investigate the associations between cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) (Aβ1-42, p-tau181), neuropsychiatric symptoms (NPS), and cognitive function across the disease spectrum.
This sample included 1772 participants from the National Alzheimer’s Coordinating Center (NACC) who had available CSF biomarker data. There is lack of standardization of CSF analysis in NACC. CSF Aβ1-42, p-tau181, and t-tau were measured using ELISA (n=276), Luminex (n=680), and Lumipulse (n=816). NPS were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factor analysis reduced NPI-Q items into a single factor. The MMSE estimated global cognition. Mediation models were estimated using the Kemeny covariance matrix in a structural equation model framework, controlling for age, education, sex, APOE ε4, and CSF assay method. Models were done in the entire sample and excluding dementia.

The sample included older adults (M=71.6, SD=8.98; 896, 50.6% females; 590, 33% dementia) who were predominantly white (n=1600, 90.3%). Lower CSF Aβ1-42 predicted higher NPI-Q scores, βz=-0.242, 95% CI:-0.312,-0.172, which was partially mediated by MMSE scores, standardized indirect effect (IEz)=-0.098, 95% CI:-0.123,-0.073. Higher CSF p-tau181 predicted higher NPI-Q scores, βz=0.127, 95% CI:0.044,0.210, which was partially mediated by MMSE scores, IEz=0.041, 95% CI:0.021,0.061. CSF t-tau did not predict NPI-Q or MMSE scores. Among those without dementia, effects were diminished and only CSF Aβ1-42 predicted higher NPI-Q scores, βz=-0.130, 95% CI:-0.248,-0.013, which was partially mediated by MMSE scores, IEz=-0.022, 95% CI:-0.036,-0.007.

NPS are likely secondary to both AD pathology and cognitive impairment. However, AD pathology likely plays less of a role in the manifestation of NPS in early disease stages.
Authors/Disclosures
Michael Walsh, Other (Boston University)
PRESENTER
Mr. Walsh has nothing to disclose.
Brandon Edward Frank, PhD (Boston University) Dr. Frank has nothing to disclose.
Landon Hurley, PhD Dr. Hurley has received personal compensation for serving as an employee of Nielsen LLC. Dr. Hurley has received personal compensation for serving as an employee of Yale University. Dr. Hurley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for iOpening Enterprises.
Kaj Blennow Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Axon, JOMDD, Roche, Siemens. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis, Julius Clinical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MagQu.
Henrik Zetterberg (Sahlgrenska University Hospital/Molndal) Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Abbvie. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Acumen. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for AlzPATH. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Annexon. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Apellis. Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Fujirebio. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens Healthineers. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.
Yorghos Tripodis Yorghos Tripodis, 5406 has nothing to disclose.
Brett Martin Brett Martin has nothing to disclose.
Jason L. Weller, MD (Boston VA Healthcare System) Dr. Weller has nothing to disclose.
Wendy Qui (Boston University School of Medicine) Prof. Qui has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. The institution of Prof. Qui has received research support from NIH.
Ann C. McKee, MD (VA Boston) Dr. McKee has nothing to disclose.
Thor D. Stein, MD, PhD (VA Boston Healthcare System) Dr. Stein has nothing to disclose.
Robert Stern, PhD (Boston University School of Medicine) Robert Stern, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Robert Stern, PhD has received research support from Eisai. The institution of Robert Stern, PhD has received research support from Lilly. The institution of Robert Stern, PhD has received research support from ATRI/NIA. Robert Stern, PhD has received publishing royalties from a publication relating to health care. Robert Stern, PhD has a non-compensated relationship as a Member with NFLPA Mackey-White Committee that is relevant to AAN interests or activities.
Jesse B. Mez, MD (Boston University School of Medicine) The institution of Dr. Mez has received research support from NIH, DOD.
Michael Alosco, PHD (Boston University ) The institution of Michael Alosco, PHD has received research support from NIH.