HAI Book 2025 - Flipbook - Page 174
Gatchel, Jennifer
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Plasma phospho-tau 217, neurofilament-light, and glial fibrillary acidic
protein are differentially associated with longitudinal neuropsychiatric
symptoms across the early cognitive spectrum
Jennifer Gatchel1,2,3, Kexin Yu4,5, Phebe Palmer3,4, Chao-Yi Wu3,4,5, Jacqueline Beltran1,4,6,
Catherine Munro1,3,7, Pia Webb3,4, Deborah Blacker1,3,4, Steven Arnold1,3,4, Gad Marshall3,4,7,
Hiroko Dodge3,4,5
1
Massachusetts General Hospital, Department of Psychiatry, Boston, MA, US
McLean Hospital, Belmont, MA, US
3
Harvard Medical School, Boston, MA, US
4
Massachusetts General Hospital, Department of Neurology, Boston, MA, US
5
Oregon Health & Science University, Portland, OR, US
6
Northeastern University, Boston, MA, US
7
Brigham and Women’s Hospital, Department of Neurology, Boston, MA, US
2
Introduction: Neuropsychiatric symptoms (NPS) are common in the preclinical and prodromal stages of
Alzheimer9s Disease and Related Dementias (ADRD) and are associated with greater cognitive and functional
decline. However, the neurobiology of these symptoms and prognostic markers of their emergence are not well
understood. We sought to examine the associations between established baseline plasma biomarkers of ADRD
and the longitudinal trajectory of NPS in older adults.
Methods: Participants were from the Massachusetts Alzheimer9s Disease Research Center longitudinal cohort. A
subset, spanning consensus diagnoses of cognitively normal (CN) (n=282, age: 68(10) years) to mild cognitive
impairment (MCI)(n=331, age:74(8) years), had baseline plasma samples assayed for phospho-tau 217 (p-Tau217),
neurofilament-light (NfL )and glial fibrillary acidic protein (GFAP) (Table 1). The average length of follow-up was
8.6±4.2 years for the CN and 7.2±4.1 years for the MCI participants. NPS were measured annually using the selfreported 15-item Geriatric Depression Scale (GDS-15) and the study-partner-reported Neuropsychiatric Inventory
Questionnaire (NPI-Q). Plasma biomarkers were log-transformed and z-scores were derived using baseline sample
values (CN + MCI). In longitudinal linear mixed-effects models, we examined the NPS measures as the dependent
variable in relation to time, plasma biomarkers, and the plasma biomarker × time interaction, controlling for age
and sex.
Results: In CN participants, baseline plasma NfL and GFAP were associated with longitudinal GDS, but not with
NPI-Q (Figure 1). In MCI participants, baseline plasma p-Tau217 and NfL were associated with GDS longitudinally,
whereas all three biomarkers (p-Tau217, NfL, GFAP) predicted increasing NPI-Q score over time (Figure 2).
Conclusions: Findings suggest differential plasma biomarker-NPS associations across the early ADRD
spectrum. Further work examining plasma biomarkers in relation to specific NPS will provide insight into the
prognostic value of these measures in predicting NPS trajectories over the course of ADRD--an area of high
potential clinical-translational impact.
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