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Updated: Jul 20, 2025

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Neuropsychiatric Symptoms and Alzheimer Disease Biomarkers Independently Predict Progression to Incident Cognitive
Ganesh M Babulal1, Ling Chen2, Samantha A Murphy3
1Department of Neurology (GMB, SAM, JCM), Washington University in St. Louis, St. Louis, MO; Institute of Public Health (GMB), Washington University in St. Louis, St. Louis, MO; Department of Psychology, Faculty of Humanities (GMB), University of Johannesburg, Johannesburg, South Africa; Department of Clinical Research and Leadership (GMB), The George Washington University School of Medicine and Health Sciences, Washington, DC.
Objectives:
To investigate the effect of neuropsychiatric symptoms and depression symptoms, respectively, and Alzheimer disease (AD) biomarkers (cerebrospinal fluid [CSF] or Positron Emission Tomography [PET] imaging) on the progression to incident cognitive impairment among cognitively normal older adults.
Design:
Prospective, observation, longitudinal study.
Setting:
Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine.
Participants:
Older adults aged 65 and above who participated in AD longitudinal studies (n = 286).
Measurements:
CSF and PET biomarkers, Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q).
Results:
Participants had an average follow-up of eight years, and 31 progressed from CDR 0 to CDR >0. After adjusting for sex, age, and education in the Cox proportional hazards survival models, neuropsychiatric symptoms as a time-dependent covariate was statistically significant in the three CSF (Aβ42/Aβ40, t-Tau/Aβ42, p-Tau/Aβ42) PET imaging models (HR = 1.33-1.50). The biomarkers were also significant as main effects (HR = 2.00-4.04). Change in depression symptoms was not significant in any models. The interactions between biomarkers and neuropsychiatric symptoms and depression were not statistically significant.
Conclusions:
Changes in neuropsychiatric symptoms increase the risk of progression to cognitive impairment among healthy, cognitively normal adults, independent of AD biomarkers. Routine assessment of neuropsychiatric symptoms could provide valuable clinical information about cognitive functioning and preclinical disease state.
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