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

NEUROBIOLOGY OF AGING

卷:65

Article

Petok, Jessica R.^1,2  Myers, Catherine E.^3,4  Pa, Judy⁵  Hobel, Zachary⁵  Wharton, David M.^6,7,8  Medina, Luis D.^6,7,9  Casado, Maria^6,7  Coppola, Giovanni^6,10  Gluck, Mark A.²  Ringman, John M.^6,7,11 

[1] St Olaf Coll, Dept Psychol, Northfield, MN 55057 USA

[2] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ USA

[3] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA

[4] Rutgers New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ USA

[5] Univ Southern Calif, Keck Sch Med, Dept Neurol, Mark & Mary Stevens Neuroimaging & Informat Inst, Los Angeles, CA 90033 USA

[6] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

[7] Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA

[8] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[9] Univ Colorado, Sch Med, Dept Neurosurg, Aurora, CO USA

[10] Univ Calif Los Angeles, Semel Inst Psychiat & Biobehav Sci, Los Angeles, CA USA

[11] Univ Southern Calif, Keck Sch Med, Dept Neurol, Memory & Aging Ctr, Los Angeles, CA 90033 USA

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

DOI  :  10.1016/j.neurobiolaging.2018.01.022

来源: Elsevier

【 摘 要 】

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. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

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