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Optimizing the preclinical Alzheimer's cognitive composite with semantic processing: The PACC5.

Kathryn V Papp1,2, Dorene M Rentz1,2, Irina Orlovsky1,2

  • 1Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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Summary

Category fluency tests detect early semantic memory decline in preclinical Alzheimer's disease. Adding this measure to cognitive composites improves detection of amyloid-related changes.

Keywords:
Alzheimer's diseaseNeuropsychological testPreclinicalSemanticVerbal fluency

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Area of Science:

  • Neuroscience
  • Cognitive Psychology
  • Gerontology

Background:

  • Amyloid-related semantic memory decline is an early indicator in preclinical Alzheimer's disease.
  • Current cognitive composites (e.g., PACC) may not fully capture early preclinical Alzheimer's changes.
  • Semantic processing measures are not integrated into standard cognitive assessments for preclinical Alzheimer's disease.

Purpose of the Study:

  • To determine if category fluency (CAT) adds independent information to the preclinical Alzheimer's cognitive composite (PACC).
  • To assess the utility of CAT in detecting amyloid-beta (Aβ)-related cognitive decline in preclinical Alzheimer's disease.

Main Methods:

  • Clinically normal older adults (Aβ+ and Aβ-) were assessed annually using neuropsychological testing.
  • Linear mixed models examined relationships between PACC, CAT, and Aβ status.
  • Participants were staged (0, 1, 2) based on neurodegeneration markers to examine early CAT decline.

Main Results:

  • Category fluency (CAT) explained unique variance in amyloid-related decline, independent of PACC.
  • Aβ+ individuals showed continued decline in CAT relative to Aβ- individuals, even after controlling for PACC.
  • Excluding CAT from PACC reduced the longitudinal Aβ+/- effect size, indicating CAT's sensitivity.
  • Decline in CAT was observed in early preclinical stages (stage 1 and 2), suggesting it is an early marker.

Conclusions:

  • The addition of CAT to the PACC enhances the detection of early Aβ-related cognitive decline.
  • CAT provides unique information not captured by episodic memory, executive function, or global cognition measures.
  • Category fluency is a valuable tool for identifying early cognitive changes in the preclinical stage of Alzheimer's disease.