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Clinical Manifestations.

Brenna Cholerton1, Gary W Beecham2, Christiane Reitz3

  • 1Department of Pathology, Stanford University, Stanford, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Neuropsychiatric symptoms (NPS) in dementia are linked to specific brain changes. Early psychosis/agitation (EPA) and late psychosis/agitation (LPA) show distinct associations with Alzheimer's disease (AD) neuropathology and other lesions.

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Area of Science:

  • Neuropathology
  • Neuroscience
  • Gerontology

Background:

  • Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD) and related dementias.
  • The timing and type of NPS may indicate different underlying pathologies and predict outcomes.
  • Understanding these associations is crucial for managing dementia burden.

Purpose of the Study:

  • To investigate the distinct associations between specific NPS clusters and neuropathologic lesions in dementia.
  • To determine if Alzheimer's disease neuropathologic change (ADNC) interacts with other lesions to influence NPS subtypes.
  • To explore the relationship between NPS timing, symptom clusters, and neuropathologic burden.

Main Methods:

  • Utilized data from the National Alzheimer's Coordinating Center (NACC) neuropathology datasets.
  • Assigned NPS subtypes (early psychosis/agitation [EPA], late psychosis/agitation [LPA], affective symptoms [AS]) using the Neuropsychiatric Inventory Questionnaire.
  • Employed adjusted logistic regression to analyze associations between NPS subtypes and neuropathologic findings.

Main Results:

  • EPA was linked to Lewy body and white matter pathology.
  • LPA showed associations with neurofibrillary tangles, neuritic plaques, Lewy bodies, and cerebral amyloid angiopathy.
  • Affective symptoms (AS) were associated with white matter disease and neurofibrillary tangles.
  • All NPS subtypes correlated with increased total neuropathologic burden.

Conclusions:

  • NPS timing and clusters have distinct associations with neuropathologic lesions, influenced by ADNC presence.
  • NPS severity increases with the number of neuropathologic changes.
  • Reducing overall neuropathologic burden may mitigate NPS and harm in dementia.