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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, and Behavioral Neurology
P10 - Poster Session 10 (8:00 AM-9:00 AM)
7-004
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.
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.
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.
No disclosure on file
No disclosure on file
Kaj Blennow Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ALZPath. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AriBio. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beckman-Coulter. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioArctic. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moleac Pte. Ltd. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurimmune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharma. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens Healthineers. 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 Abbvie. 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 AC Immune. 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 ALZPath. 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 AriBio. 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 Beckman-Coulter. 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 BioArctic. 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 Biogen. 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 Eisai. 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 Lilly. 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 Moleac Pte. Ltd. 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 Neurimmune. 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. 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 Ono Pharma. 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 Prothena. 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 Quanterix. 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 Roche Diagnostics. 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 Sanofi. 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 Siemens Healthineers. 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 Julius Clinical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Celdara Medical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Co-founder with Brain Biomarker Solutions.
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 Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. 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 Wiley and Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.
Yorghos Tripodis Yorghos Tripodis has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Medical Association.
No disclosure on file
Jason Weller, MD (University of Florida Health) Dr. Weller has nothing to disclose.
No disclosure on file
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. The institution of Michael Alosco, PhD has received research support from Life Molecular Imaging Inc.