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Comparison of Semantic and Episodic Memory BOLD fMRI Activation in Predicting Cognitive Decline in Older Adults

  • Nathan Hantke (a1), Kristy A. Nielson (a1) (a2), John L. Woodard (a3), Leslie M. Guidotti Breting (a4), Alissa Butts (a1), Michael Seidenberg (a4), J. Carson Smith (a5), Sally Durgerian (a2), Melissa Lancaster (a4), Monica Matthews (a4), Michael A. Sugarman (a3) and Stephen M. Rao (a6)...


Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease. (JINS, 2012, 18, 1–11)

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Corresponding author

Correspondence and reprint requests to: Stephen M. Rao, Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue/U10, Cleveland, OH 44195. E-mail:


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Comparison of Semantic and Episodic Memory BOLD fMRI Activation in Predicting Cognitive Decline in Older Adults

  • Nathan Hantke (a1), Kristy A. Nielson (a1) (a2), John L. Woodard (a3), Leslie M. Guidotti Breting (a4), Alissa Butts (a1), Michael Seidenberg (a4), J. Carson Smith (a5), Sally Durgerian (a2), Melissa Lancaster (a4), Monica Matthews (a4), Michael A. Sugarman (a3) and Stephen M. Rao (a6)...


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