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Clinical Manifestations.

Adrienne L Atayde1, Neda Rashidi-Ranjbar1, Marc A Khoury1,2

  • 1Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Neuropsychiatric symptoms in Alzheimer's disease are linked to clinical diagnosis and specific pathologies. Neuropathology and diagnosis show independent effects on symptoms like apathy and delusions.

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Area of Science:

  • Neurology
  • Neuroscience
  • Gerontology

Background:

  • Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD), affecting disease progression and quality of life.
  • Both AD pathology (amyloid, tau) and TDP-43 neuropathology may contribute to NPS.
  • The National Alzheimer's Coordinating Center (NACC) database was utilized to investigate these relationships.

Purpose of the Study:

  • To explore the associations between NPS and Alzheimer's disease (AD) pathology.
  • To investigate the role of TDP-43 neuropathology in NPS.
  • To examine the influence of clinical diagnosis on NPS in the context of neuropathology.

Main Methods:

  • Analysis of 1391 participants from the NACC database.
  • Utilized logistic and linear regression models to assess associations between NPS, clinical diagnosis, and neuropathology.
  • Adjusted for age, sex, education, cognitive scores, and APOE e4 status.

Main Results:

  • Clinical diagnosis was consistently associated with various NPS domains.
  • Both clinical diagnosis and neuropathology significantly correlated with apathy and delusions.
  • Interaction effects between neuropathology and clinical diagnosis were observed for apathy and delusions, with clinical diagnosis also impacting NPS severity.

Conclusions:

  • Clinical diagnosis plays a significant role in NPS across multiple domains.
  • AD and TDP-43 neuropathology, along with demographic factors, have domain-specific effects on NPS, particularly delusions and apathy.
  • Pathology and clinical diagnosis appear to have independent effects on NPS, warranting further longitudinal investigation.