2024-Abstract 4

by | Sep 10, 2024 | 2024 Abstracts

Abstract 4
Category: Basic Science

At the end of the session, participants will be able to:

  1. Identify the core features of cognitive impairment, including domain-specific measures through targeted clinical testing, in chronic schizophrenia and its prevalence among patients.

  2. Distinguish between the neuropathological changes associated with cognitive impairment in chronic schizophrenia and those typically seen in neurodegenerative conditions like Alzheimer’s Disease.

  3. Compare the capacity of commonplace neuropathological diagnostic tools to accurately predict clinical cognitive impairment in this patient population compared to the general ageing population.

  4. Analyze the relationship between patient characteristics, neurocognitive testing, and neuropathology on autopsy in understanding the cellular mechanisms underlying cognitive impairment in schizophrenia.

  5. Evaluate the use of advanced data analysis techniques, such as regression models, UMAP, and k-means clustering, in identifying subpopulations within the schizophrenia patient cohort and their potential clinical utility.

  6. Discuss potential implications of this research for developing novel precision medicine approaches targeting cognitive impairment in schizophrenia from a neuropathological standpoint.

COI Disclosure:

None to disclose.

Presenter

Naomi (Catie) Futhey is a third-year MD/PhD student at The University of British Columbia in the Graduate Program in Neuroscience. She is co-supervised by Dr. Veronica Hirsch-Reinshagen and Dr. Mark Cembrowski and her project aims to understand the cellular underpinnings of schizophrenia and Alzheimer’s Disease.

Naomi C. Futhey1, Elizabeth Gregory1,3, Belen Arranz4, Josep Maria Haro4, Fidel Vila-Rodriguez3,5, Mark S. Cembrowski2,5,6,7, and Veronica Hirsch-Reinshagen8

 

  1. MD/PhD Program, University of British Columbia, Vancouver, Canada
  2. Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada
  3. Non-Invasive Neurostimulation Therapies Laboratory, Department of Psychiatry, University of British Columbia, Vancouver, Canada
  4. Sant Joan de Déu, Serveis de Salut Mental, Barcelona, Spain
  5. School of Biomedical Engineering, University of British Columbia, Vancouver, Canada
  6. Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
  7. Department of Mathematics, University of British Columbia, Vancouver, Canada.
  8. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

Target Audience:
Pathologists, Residents, Medical Students

CanMEDS:
Scholar

Unique neuropathological mechanisms underlying cognitive impairment in schizophrenia

Abstract

Cognitive impairment is a core tenet of chronic schizophrenia, impacting as many as 98% of patients. It is not targeted by any currently available therapies, and the underlying neuropathology only occasionally includes neurodegenerative processes such as Alzheimer’s Disease. This study seeks to understand the cellular mechanisms for cognitive impairment which may be unique to schizophrenia. Demographic, clinical, and autopsy data were obtained for 55 elderly patients with chronic schizophrenia and post-mortem neuropathological evaluation, with additional neuropsychological testing conducted during life in a subset. Standard evaluation of neurodegenerative conditions and exploratory data analyses including clinical-pathological correlations were performed. Further dimensionality reduction and clustering analysis were conducted using Uniform Manifold Approximation and Projection (UMAP) and k-means clustering to illustrate characteristics of patient subpopulations. On average, patients experienced multiple decades of symptoms, with marked disruption of reality by hallucinations and delusions. Scoring of negative symptoms at this advanced disease stage outweighed that of positive symptoms, although both were present. Significant cognitive impairment was noted across different neuropsychological testing modalities. Only 56% of patients had sufficiently severe neuropathological changes to explain their cognitive impairment, and distinct subpopulations were highlighted in clustering analysis. Together, this suggests the presence of additional mechanisms underlying cognitive impairment in chronic schizophrenia. Better understanding of the pathophysiology of this impairment may inform our knowledge of schizophrenia as a whole and provide the basis for novel precision medicine applications.