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Clinical Manifestations.

Laura Del Hoyo1,2, Katja Sandkühler3, Laura Videla4,5

  • 1Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain.

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

Standardizing intellectual disability (ID) classification is crucial for accurate Alzheimer's disease (AD) diagnosis in individuals with Down syndrome (DS). Discrepancies between sites can lead to misclassification and unreliable diagnostic cut-offs.

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Area of Science:

  • Neurology
  • Genetics
  • Psychiatry

Background:

  • Alzheimer's disease (AD) diagnosis in Down syndrome (DS) often relies on cognitive assessment cut-offs stratified by intellectual disability (ID) levels.
  • Site-specific ID classification discrepancies can lead to misdiagnosis when applying these cut-offs.

Purpose of the Study:

  • To evaluate the impact of inter-site ID classification discrepancies on Alzheimer's disease dementia diagnostic cut-offs (CAMCOG-DS) in adults with Down syndrome.
  • To assess the generalizability of site-specific diagnostic criteria.

Main Methods:

  • A dual-center cohort study of 673 adults with mild to moderate ID across different stages of AD.
  • Analysis of inter-rater agreement for ID classification within and between sites.
  • Receiver Operating Characteristic (ROC) analysis to derive CAMCOG-DS cut-offs and assess their performance when applied across cohorts.

Main Results:

  • High agreement (95%) for ID classification within sites, but lower agreement (60%) between sites.
  • ID classification discrepancies resulted in higher CAMCOG-DS cut-offs in Barcelona compared to Munich for mild and moderate ID.
  • Applying site-specific cut-offs to an external cohort significantly reduced diagnostic sensitivity and specificity.

Conclusions:

  • Standardization of intellectual disability classification is essential for developing reliable and generalizable cut-offs for diagnosing AD dementia in Down syndrome.
  • Neuropsychological assessment in Down syndrome requires consistent ID stratification for accurate Alzheimer's disease diagnosis.