TitleImpairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers.
Publication TypeJournal Article
Year of Publication2018
AuthorsPetok JR, Myers CE, Pa J, Hobel Z, Wharton DM, Medina LD, Casado M, Coppola G, Gluck MA, Ringman JM
JournalNeurobiol Aging
Date Published2018 May

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.

Alternate JournalNeurobiol. Aging
PubMed ID29494861
PubMed Central IDPMC5871602
Grant ListUL1 RR033176 / RR / NCRR NIH HHS / United States
U01 AG032438 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
R03 AG044610 / AG / NIA NIH HHS / United States
R56 AG053961 / AG / NIA NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
K08 AG022228 / AG / NIA NIH HHS / United States