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Basic Science and Pathogenesis.

Willem L Hartog1,2, Georgia Malliou1,2, Michelle C Barboure2,3

  • 1Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Netherlands.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Dementia diagnoses often involve multiple co-pathologies, but these did not explain diagnostic discrepancies. Further research into co-pathology severity may clarify links between brain pathology and clinical presentation in dementia.

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Dementia Research

Background:

  • Post-mortem brain tissue analysis reveals significant biological heterogeneity in dementia.
  • Multiple coexisting pathologies are common across different dementia diagnoses.
  • The impact of specific pathologies on clinical diagnosis accuracy is not fully understood.

Purpose of the Study:

  • To investigate the relationship between co-pathologies and diagnostic concordance in dementia patients.
  • To determine if the presence of multiple pathologies influences the accuracy of ante-mortem clinical diagnoses.
  • To explore factors contributing to discordance between clinical and pathological diagnoses in dementia.

Main Methods:

  • Clinical and pathological diagnostic data from 202 dementia patients were analyzed.
  • Post-mortem autopsy reports from the Netherlands Brain Bank were utilized.
  • Pearson chi-square tests compared co-pathology counts in concordant versus discordant diagnostic groups.

Main Results:

  • Alzheimer's disease (AD), frontotemporal lobar degeneration-tau (FTLD-TDP), and Lewy body dementia (LBD) were the most frequent primary pathologies.
  • 78% of cases showed concordance between clinical and primary pathological diagnoses.
  • Co-pathologies were frequent in all groups, particularly LBD (91%), AD (82%), and FTLD-TDP (79%).
  • No significant difference in the number of co-pathologies was found between concordant and discordant cases.
  • Age at death did not differ between concordant and discordant groups.

Conclusions:

  • Dementia is characterized by pathological heterogeneity, with neurodegenerative diseases rarely occurring in isolation.
  • The number of co-pathologies or age at death did not explain diagnostic discordance.
  • Investigating co-pathology severity may offer insights into clinical-pathological interactions in dementia phenotypes.