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  • 1Washington University in St. Louis School of Medicine, St. Louis, MO, USA.

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Summary
This summary is machine-generated.

Premorbid intellectual impairment (PII) influences cognitive decline timing in people with Down syndrome (DS), but not Alzheimer's disease (AD) biomarker pathology. Considering PII is crucial for clinical trials in DS.

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Area of Science:

  • Neuroscience
  • Genetics
  • Clinical Medicine

Background:

  • Down syndrome (DS) is characterized by lifelong intellectual impairment.
  • Individuals with DS have a higher risk of Alzheimer's disease (AD) dementia, typically manifesting in their 50s.
  • Previous studies suggested premorbid intellectual impairment (PII) did not influence cognitive decline in DS.

Purpose of the Study:

  • To longitudinally assess the influence of PII on cognitive and biomarker trajectories in individuals with DS.
  • To determine if PII affects the timing and rate of cognitive decline associated with AD.
  • To investigate the impact of PII on AD-related biomarker changes.

Main Methods:

  • Longitudinal data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) study (N≤455) were analyzed.
  • Generalized additive mixed-models (GAMMs) were used to compare cognitive and biomarker trajectories between mild and moderate/severe PII groups.
  • Cognitive function was assessed using the modified Cued Recall Task (mCRT) and Down Syndrome Mental Status Exam (DSMSE).
  • Plasma and neuroimaging markers of amyloid, tau, and neurodegeneration were evaluated.

Main Results:

  • Cognitive performance trajectories differed significantly based on PII levels.
  • Individuals with mild PII experienced cognitive decline approximately 2.6 years later (55.2 years) compared to those with moderate/severe PII (52.6 years).
  • PII did not significantly impact amyloid, tau, or neurodegeneration biomarker trajectories.

Conclusions:

  • The timing and slope of cognitive decline in individuals with DS vary with PII.
  • Alzheimer's disease biomarker pathology trajectories are not influenced by PII.
  • PII should be considered when using cognitive measures for staging or as endpoints in clinical trials for Down syndrome.