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Neurobiol Aging. 2018 May;65:149-157. doi: 10.1016/j.neurobiolaging.2018.01.022. Epub 2018 Feb 8.

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

Author information

1
Department of Psychology, Saint Olaf College, Northfield, MN, USA; Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA. Electronic address: petok@stolaf.edu.
2
Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, USA; Department of Pharmacology, Physiology & Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ, USA.
3
Mark and Mary Stevens Neuroimaging and Informatics Institute, Department of Neurology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
4
Department of Neurology, UCLA, Los Angeles, CA, USA; Easton Center for Alzheimer's Disease Research, Los Angeles, CA, USA; Vanderbilt University, Nashville, TN, USA.
5
Department of Neurology, UCLA, Los Angeles, CA, USA; Easton Center for Alzheimer's Disease Research, Los Angeles, CA, USA; Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA.
6
Department of Neurology, UCLA, Los Angeles, CA, USA; Easton Center for Alzheimer's Disease Research, Los Angeles, CA, USA.
7
Department of Neurology, UCLA, Los Angeles, CA, USA; Semel Institute of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
8
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
9
Department of Neurology, UCLA, Los Angeles, CA, USA; Easton Center for Alzheimer's Disease Research, Los Angeles, CA, USA; Memory and Aging Center, Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Abstract

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.

KEYWORDS:

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

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