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Cited by 303Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

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

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Papp, Kathryn V., Rentz, Dorene M., Orlovsky, Irina, Sperling, Reisa A., Mormino, Elizabeth C.·2017·Alzheimer's & Dementia: Translational Research & Clinical Interventions
DOI 10.1016/j.trci.2017.10.004PMC PMC5726754
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Abstract

Introduction: Amyloid‐related decline in semantic memory was recently shown to be observable in the preclinical period of Alzheimer's disease. Cognitive composites designed to be sensitive to cognitive change in preclinical Alzheimer's disease (e.g., preclinical Alzheimer's cognitive composite [PACC]) and currently used in secondary prevention trials do not currently integrate measures of semantic processing. Our objective was to determine whether a standard semantic measure (i.e., category fluency [CAT] to animals, fruits, and vegetables) adds independent information above and beyond Aβ‐related decline captured by the PACC. Methods: Clinically normal older adults from the Harvard Aging Brain Study were identified at baseline as Aβ+ (n = 70) or Aβ− (n = 209) using Pittsburgh compound B–positron emission tomography imaging and followed annually with neuropsychological testing for 3.87 ± 1.09 years. The relationships between PACC, CAT, and variations of the PACC including/excluding CAT were examined using linear mixed models controlling for age, sex, and education. We additionally examined decline on CAT by further grouping Aβ+ participants into preclinical stage 1 and stage 2 on the basis of neurodegeneration markers. Results: CAT explained unique variance in amyloid‐related decline, with Aβ+'s continuing to decline relative to Aβ−'s in CAT even after controlling for overall PACC decline. In addition, removal of CAT from the PACC resulted in a longitudinal Aβ+/− effect size reduction of 20% at 3‐year follow‐up and 12% at 5‐year follow‐up. Finally, both stage 1 and stage 2 participants declined on CAT in comparison with stage 0, suggesting CAT declines early within the preclinical trajectory. Conclusion: Addition of CAT to the PACC provides unique information about early cognitive decline not currently captured by the episodic memory, executive function, and global cognition components and may therefore improve detection of early Aβ‐related cognitive decline.

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Authors
Papp, K. V., Rentz, D. M., Orlovsky, I., Sperling, R. A., & Mormino, E. C.
Affiliations
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
Corresponding author
Papp, Kathryn V.
ORCID
Venue
Alzheimer's & Dementia: Translational Research & Clinical Interventions
Publisher
Wiley
Published
2017-11
Volume
3
Issue
4
Pages
668-677
ISSN
2352-8737 (ISSN-L)
DOI
10.1016/j.trci.2017.10.004
PMC
PMC5726754
OpenAlex
W2767453481
Cited by
303
References
41
Citations by year
2026: 43 · 2025: 50 · 2024: 51 · 2023: 44 · 2022: 54 · 2021: 26 · 2020: 15 · 2019: 14 · 2018: 6
FWCI
7.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institute on Aging (K23 AG053422‐01)
  • National Institutes of Health (P01 AG036694, R01 MH090291, U01 AG024904, R01 AG027435, R01 AG037497, P50 AG005134, U01 AG032438, R01 AG034556, K24 AG035007, U19 AG010483, K01 AG051718)
  • Fidelity Biosciences
  • Harvard NeuroDiscovery Center
  • Janssen Pharmaceuticals
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
preclinical Alzheimer's disease, semantic memory, semantic fluency, amyloid-beta, cognitive decline, Pittsburgh compound B, neurodegeneration biomarkers

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