Objective: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more in Alzheimer's disease (AD). The symptom-based cluster including nighttime disturbances, depression, appetite changes, anxiety, and apathy (affective and vegetative symptoms) was associated with an increased risk of dementia in MCI and has common neuroanatomical associations. Our objective was to investigate the differences in brain morphology associations with affective and vegetative symptoms between three groups: cognitively normal older adults (CN), MCI and AD. Material and Methods: Alzheimer's Disease Neuroimaging Initiative data of 223 CN, 367 MCI and 175 AD, including cortical volumes, surface areas and thicknesses and severity scores of the five NPS were analyzed. A whole-brain vertex-wise general linear model was performed to test for intergroup differences (CN-MCI, CN-AD, AD-MCI) in brain morphology associations with five NPS. Multiple regressions were conducted to investigate cortical change as a function of NPS severity in the AD-MCI contrast. Results: We found (1) signature differences in nighttime disturbances associations with prefrontal regions in AD-MCI, (2) signature differences in NPS associations with temporal regions in AD-MCI for depression and in CN-AD for anxiety, (3) decreased temporal metrics in MCI as nighttime disturbances and depression severity increased, (4) decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. Conclusion: Each NPS seems to have a signature on brain morphology. Affective and vegetative NPS were primarily associated with prefrontal and temporal regions. These signatures open the possibility of potential future assessments of links between brain morphology and NPS on an individual level.

Original languageEnglish
Article numbere5952
JournalInternational Journal of Geriatric Psychiatry
Issue number6
StatePublished - Jun 2023


  • Alzheimer's disease
  • brain morphology
  • magnetic resonance imaging
  • mild cognitive impairment
  • neuroanatomy
  • neuropsychiatric symptoms


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