Interactions Between Neuropsychiatric Symptoms and Alzheimer's Disease Neuroimaging Biomarkers in Predicting Longitudinal Cognitive Decline

  • Anna Pink (First author)
  • , Janina Krell-Roesch
  • , Jeremy A Syrjanen
  • , Luke R Christenson
  • , Val J Lowe
  • , Prashanthi Vemuri
  • , Julie A Fields
  • , Gorazd B Stokin
  • , Walter K Kremers
  • , Eugene L Scharf
  • , Clifford R Jack
  • , David S Knopman
  • , Ronald C Petersen
  • , Maria Vassilaki
  • , Yonas E Geda

Research output: Contribution to journalOriginal Articlepeer-review

Abstract

OBJECTIVE: To examine interactions between Neuropsychiatric symptoms (NPS) with Pittsburgh Compound B (PiB) and fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting cognitive trajectories.

METHODS: We conducted a longitudinal study in the setting of the population-based Mayo Clinic Study of Aging in Olmsted County, MN, involving 1581 cognitively unimpaired (CU) persons aged ≥50 years (median age 71.83 years, 54.0% males, 27.5% APOE ɛ4 carriers). NPS at baseline were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Brain glucose hypometabolism was defined as a SUVR ≤ 1.47 (measured by FDG-PET) in regions typically affected in Alzheimer's disease. Abnormal cortical amyloid deposition was measured using PiB-PET (SUVR ≥ 1.48). Neuropsychological testing was done approximately every 15 months, and we calculated global and domain-specific (memory, language, attention, and visuospatial skills) cognitive z-scores. We ran linear mixed-effect models to examine the associations and interactions between NPS at baseline and z-scored PiB- and FDG-PET SUVRs in predicting cognitive z-scores adjusted for age, sex, education, and previous cognitive testing.

RESULTS: Individuals at the average PiB and without NPS at baseline declined over time on cognitive z-scores. Those with increased PiB at baseline declined faster (two-way interaction), and those with increased PiB and NPS declined even faster (three-way interaction). We observed interactions between time, increased PiB and anxiety or irritability indicating accelerated decline on global z-scores, and between time, increased PiB and several NPS (e.g., agitation) showing faster domain-specific decline, especially on the attention domain.

CONCLUSIONS: NPS and increased brain amyloid deposition synergistically interact in accelerating global and domain-specific cognitive decline among CU persons at baseline.

Original languageEnglish
Pages (from-to)4-15
Number of pages12
JournalPsychiatric Research and Clinical Practice
Volume5
Issue number1
DOIs
Publication statusPublished - 2023

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