Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging

Janina Krell-Roesch, Jeremy A. Syrjanen, Mary M. Machulda, Teresa J. Christianson, Walter K. Kremers, Michelle M. Mielke, David S. Knopman, Ronald C. Petersen, Maria Vassilaki, Yonas E. Geda

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain-specific cognitive trajectories. Methods: In this longitudinal study conducted in the setting of the population-based Mayo Clinic Study of Aging, 5081 community-dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI-Q), and Beck Depression and Anxiety Inventories (BDI-II, BAI). Global and domain-specific (memory, language, attention, and visuospatial skills) cognitive performance was assessed through neuropsychological testing every 15 months. Associations between baseline NPS and trajectories for individual yearly change in cognitive z-scores were calculated using linear mixed-effect models. Results: Cognition declined regardless of NPS status over the median follow-up of 4.5 years. Presence of NPS was associated with increased cognitive decline. Differences in annualized change in global cognition z-scores for participants with NPS compared to without NPS ranged from −0.018 (95% CI −0.032, −0.004; p = 0.011) for irritability to −0.159 (−0.254, −0.065; p = 0.001) for hallucinations. Associations between NPS and annual decline in global cognition were significant for most NPI-Q-assessed NPS and clinical depression (BDI-II≥13). Participants with NPI-Q-assessed depression, apathy, nighttime behavior, and clinical depression had greater decline in all domain-specific z-scores; presence of delusions and anxiety was associated with more pronounced decline in language, attention and visuospatial skills. Conclusion: NPS were associated with a more accelerated cognitive decline. Clinical assessment and potential treatment of NPS is warranted even in a community setting as NPS may impact cognitive decline in nondemented individuals.

Original languageEnglish (US)
Pages (from-to)1362-1369
Number of pages8
JournalInternational Journal of Geriatric Psychiatry
Issue number9
StatePublished - Sep 2021


  • cognitive trajectory
  • longitudinal study
  • neuropsychiatric symptoms
  • nondemented
  • older adults

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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