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Effect of Knowledge of APOE Genotype on Subjective and Objective Memory Performance in Healthy Older Adults
Tara T. Lineweaver, Ph.D.; Mark W. Bondi, Ph.D.; Douglas Galasko, M.D.; David P. Salmon, Ph.D.
Am J Psychiatry 2014;171:201-208. doi:10.1176/appi.ajp.2013.12121590
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Dr. Galasko has served on advisory panels for Elan Pharmaceuticals and Neurophage and on data and safety monitoring boards for clinical trials for Balance Pharmaceuticals, Elan Pharmaceuticals, Janssen Immunotherapy, and Pfizer. Dr. Salmon has served as a consultant for Bristol-Myers Squibb. The other authors report no financial relationships with commercial interests.

Supported by National Institute on Aging grants P50-AG 05131, R01-AG 012674, and K24-AG 026431 and an Alzheimer’s Centers of California grant from the State of California.

From the Department of Psychology, Butler University, Indianapolis; the Departments of Psychiatry and Neurosciences, University of California, San Diego; and the Psychology and Neurology Services, VA San Diego Healthcare System, San Diego.

Address correspondence to Dr. Salmon (dsalmon@ucsd.edu).

Copyright © 2014 by the American Psychiatric Association

Received December 19, 2012; Revised July 30, 2013; Accepted August 12, 2013.


Objective  The knowledge that one carries the apolipoprotein E (APOE) ε4 allele risk factor for Alzheimer’s disease was recently found to have little short-term psychological risk. The authors investigated the impact of knowledge of carrying the risk allele on subjective ratings of memory and objective memory test performance of older adults.

Method  Using a nested case-control design, the authors administered objective verbal and visual memory tests and self-rating scales of memory function to 144 cognitively normal older adults (ages 52–89) with known APOE genotype who knew (ε4+, N=25; ε4−, N=49) or did not know (ε4+, N=25; ε4−, N=45) their genotype and genetic risk for Alzheimer’s disease prior to neuropsychological evaluation.

Results  Significant genotype-by-disclosure interaction effects were observed on several memory rating scales and tests of immediate and delayed verbal recall. Older adults who knew their ε4+ genotype judged their memory more harshly and performed worse on an objective verbal memory test than did ε4+ adults who did not know. In contrast, older adults who knew their ε4− genotype judged their memory more positively than did ε4− adults who did not know, but these groups did not differ in objective memory test performance.

Conclusions  Informing older adults that they have an APOE genotype associated with an increased risk of Alzheimer’s disease can have adverse consequences on their perception of their memory abilities and their performance on objective memory tests. The patient’s knowledge of his or her genotype and risk of Alzheimer’s disease should be considered when evaluating cognition in the elderly.

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FIGURE 1. Scores on the Capacity Scale of the Metamemory in Adulthood Questionnaire for Participants With (ε4+ ) or Without (ε4−) the APOE ε4 Allele Who Knew (Informed) or Did Not Know (Not Informed) Their APOE Genotypea

a Error bars represent standard deviation.

FIGURE 2. Memory Functioning Questionnaire Scores for Participants With (ε4+ ) or Without (ε4−) the APOE ε4 Allele Who Knew (Informed) or Did Not Know (Not Informed) Their APOE Genotypea

a Error bars represent standard deviation.

FIGURE 3. Scores on Immediate and Delayed Recall From the Logical Memory Subtest for Participants With (ε4+ ) or Without (ε4−) the APOE ε4 Allele Who Knew (Informed) or Did Not Know (Not Informed) Their APOE Genotypea

a Error bars represent standard deviation.

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TABLE 1.Demographic and Clinical Characteristics of Participants With (ε4+ ) or Without (ε4−) the APOE ε4 Allele Who Knew (Informed) or Did Not Know (Not Informed) Their APOE Genotypea
Table Footer Note

a No significant differences between groups on any variable.

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TABLE 2.Scores on the Metamemory in Adulthood Questionnaire and Memory Functioning Questionnaire and on Verbal and Visual Memory Tests for Participants With (ε4+ ) or Without (ε4−) the APOE ε4 Allele Who Knew (Informed) or Did Not Know (Not Informed) Their APOE Genotype
Table Footer Note

a Significantly different between groups, p<0.05.



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Among cognitively normal older adults with an APOE ɛ4 genotype, putting them at increased risk of Alzheimer's disease, how did performance on an objective verbal memory test differ between those informed versus uninformed of the risk genotype?
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How did disclosing an APOE ε4 genotype to a cognitively normal elderly adult affect self-reported depression on the Geriatric Depression Scale?
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