2025 – Abstract 6

by | Sep 24, 2025 | 2025 Abstracts

Abstract 6
Category: Basic Science

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

  1. Describe the distinct cognitive subtypes identified in late-life schizophrenia using k-means clustering by neuropsychological test scores.
  2. Interpret the clinicopathologic associations between cerebrovascular disease and cognitive performance in older patients with chronic schizophrenia.
  3. Evaluate the potential of cognitive subtyping as a tool to stratify schizophrenia patients by underlying neuropathological mechanisms.

COI Disclosure:

None to disclose.

Presenter

Naomi (Catie) Futhey is an MD/PhD candidate at the University of British Columbia, co-supervised by Dr. Veronica Hirsch-Reinshagen and Dr. Mark Cembrowski. Her doctoral research investigates spatial proteomic disease signatures in the human brain, with a focus on how vascular, inflammatory, and hormonal factors contribute to cognitive decline in chronic brain disorders such as schizophrenia and Alzheimer’s disease. She is particularly interested in sex-based differences in health and disease as a critical pathway toward achieving truly personalized and holistic medicine. Naomi also serves on the Clinician Investigator Trainee Association of Canada (CITAC) Board of Directors and is a strong advocate for integrated physician-scientist training and women’s heart and brain health.

Naomi C. Futhey1-3, Fidel Vila-Rodriguez4,5, Shawn J. Stochmanski4, Elizabeth Gregory4, William Honer4, Belen Arranz6,7, Belen Ramos6-8, Ana Escanilla6, America Vera-Montecinos8,9, Mark S. Cembrowski1,2,5,10, and Veronica Hirsch-Reinshagen3

  1. Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada 
  2. Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, Canada
  3. Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
  4. Department of Psychiatry, University of British Columbia, Vancouver, Canada
  5. School of Biomedical Engineering, University of British Columbia, Vancouver, Canada
  6. Parc Sanitari Sant Joan de Déu, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Spain
  7. Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Ministry of Economy, Industry and Competitiveness Institute of Health Carlos III, Madrid, Spain
  8. Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950 Esplugues de Llobregat, Spain
  9. Departamento de Ciencias Biológicas y Químicas, Facultad De Ciencias, Universidad San Sebastián, Sede Tres Pascualas Lientur 1457, Concepción 4080871, Chile
  10. Department of Mathematics, University of British Columbia, Vancouver, Canada

Target Audience:
Pathologists, Residents, Medical Students

CanMEDS:
Medical Expert (the integrating role), Collaborator, Scholar

Cognitive subtyping in schizophrenia reveals distinct clinicopathologic signatures and a vascular-linked cognitive phenotype

Abstract

Cognitive impairment is a defining feature of chronic schizophrenia, but its underlying neuropathology remains unclear and treatment options are scarce. The contributions of Alzheimer’s disease (AD) and cerebrovascular disease (CVD) pathology to cognitive decline in older patients are particularly understudied. This study examined the relationship between postmortem neuropathology and neuropsychological performance in 55 patients (mean age 78), representing, to our knowledge, the most detailed clinicopathologic investigation of late-life schizophrenia to date. Although 70% met criteria for cognitive impairment, the prevalence of AD pathology (35.1%) was comparable to that reported in age-matched controls. In contrast, CVD pathology was more frequent (84.2%) and significantly associated with lower Mini-Mental State Examination (MMSE) scores (B = -6.40, p < 0.001), after adjusting for age and education. No other significant pathology-cognition associations were found. Notably, 42% of cognitively impaired individuals lacked traditional neuropathological findings to explain their symptoms. k-means clustering of cognitive test scores revealed three cognitive subtypes with distinct clinical profiles, despite comparable degrees of neuropathological burden. The MMSE-CVD association was specific to one group (NCOG_3), which showed domain-selective impairments, implicating vascular pathology in a distinct cognitive phenotype. NCOG_1 exhibited global cognitive deficits independent of all evaluated pathologies, while NCOG_2 demonstrated relatively preserved cognition and younger age at death. These findings reveal a novel, subtype-specific association between cognition and postmortem CVD pathology in chronic schizophrenia and suggest that cognitive subtyping may help stratify patients by underlying disease mechanism. Addressing cardiovascular risk may therefore represent a modifiable therapeutic target for cognitive symptoms in select patients.