Impairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers

Jessica R. Petok, Catherine E. Myers, Judy Pa, Zachary Hobel, David M. Wharton, Luis D. Medina, Maria Casado, Giovanni Coppola, Mark A. Gluck, John M. Ringman

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Fast, inexpensive, and noninvasive identification of Alzheimer's disease (AD) before clinical symptoms emerge would augment our ability to intervene early in the disease. Individuals with fully penetrant genetic mutations causing autosomal dominant Alzheimer's disease (ADAD) are essentially certain to develop the disease, providing a unique opportunity to examine biomarkers during the preclinical stage. Using a generalization task that has previously shown to be sensitive to medial temporal lobe pathology, we compared preclinical individuals carrying ADAD mutations to noncarrying kin to determine whether generalization (the ability to transfer previous learning to novel but familiar recombinations) is vulnerable early, before overt cognitive decline. As predicted, results revealed that preclinical ADAD mutation carriers made significantly more errors during generalization than noncarrying kin, despite no differences between groups during learning or retention. This impairment correlated with the left hippocampal volume, particularly in mutation carriers. Such identification of generalization deficits in early ADAD may provide an easily implementable and potentially linguistically and culturally neutral way to identify and track cognition in ADAD.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalNeurobiology of Aging
StatePublished - May 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


  • Alzheimer's disease
  • Amyloid precursor protein
  • Associative learning
  • Early onset
  • Generalization
  • Hippocampus
  • Mutation
  • Preclinical
  • Presenilin 1

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