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Cognitive Discrepancies Versus APOE Genotype as Predictors of Cognitive Decline in Normal-Functioning Elderly Individuals: A Longitudinal Study

Eric M. Fine, Ph.D., Dean C. Delis, Ph.D., Spencer R. Wetter, Ph.D., Mark W. Jacobson, Ph.D., Amy J. Jak, Ph.D., Carrie R. McDonald, Ph.D., Jodessa C. Braga, B.A., Leon J. Thal, M.D., David P. Salmon, Ph.D., and Mark W. Bondi, Ph.D.

From the Veterans Affairs San Diego Healthcare System (EMF, DCD, SRW, MWJ, AJJ, JCB, MWB); Departments of Psychiatry (DCD, SRW, MWJ, CRM, MWB) and Neurosciences (LJT, DPS), School of Medicine, University of California, San Diego, CA.

Objectives: Cognitive-discrepancy analysis has been shown to be a useful technique for detecting subtle cognitive deficits in normal-functioning elderly individuals who are genetically at-risk for Alzheimer disease (AD). However, studies that have used cognitive-discrepancy measures to date have used retrospective or cross-sectional designs, and the utility of this approach to predict cognitive decline has not been examined in a prospective investigation.

Design: Longitudinal study.

Setting: San Diego, CA, Veterans Administration Hospital.

Participants: Twenty-four normal-functioning elderly individuals participated in the study, with 16 subjects exhibiting no change in their Dementia Rating Scale (DRS) scores over an 1-year period (Stable Group), and 8 subjects exhibiting a decline in DRS scores over the 1-year period (Decline group).

Measurements: A cognitive-discrepancy measure isolating cognitive switching was computed that contrasted performance on a new higher-level task of executive functioning (a Stroop/Switching measure) relative to a composite measure of lower-level Stroop conditions.

Results: a) In the year before their cognitive changes, the Decline group exhibited a significantly larger cognitive-discrepancy (Stroop/Switching versus lower-level Stroop conditions) score compared with a control (Stable) group; and b) the cognitive-discrepancy measure was superior to APOE genotype in predicting DRS decline.

Conclusion: Cognitive-discrepancy analysis isolating a component executive function ability not only seems to be a useful tool for identifying individuals at risk for cognitive deficits, but also shows promise in predicting individuals who may show subtle cognitive decline over time.

Key Words: Cognitive discrepancies • aging • Alzheimer disease • executive functioning

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