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Amyloid Burden, Neuronal Function, and Cognitive Decline in Middle-Aged Adults at Risk for Alzheimer's Disease

  • Ozioma C. Okonkwo (a1) (a2) (a3), Jennifer M. Oh (a1) (a2), Rebecca Koscik (a3), Erin Jonaitis (a3), Caitlin A. Cleary (a1) (a2), N. Maritza Dowling (a2) (a4), Barbara B. Bendlin (a1) (a2) (a3), Asenath LaRue (a3), Bruce P. Hermann (a2) (a3) (a5), Todd E. Barnhart (a6), Dhanabalan Murali (a6), Howard A. Rowley (a2) (a7), Cynthia M. Carlsson (a1) (a2) (a3), Catherine L. Gallagher (a1) (a2) (a5), Sanjay Asthana (a1) (a2) (a3), Mark A. Sager (a2) (a3), Brad T. Christian (a2) (a6) and Sterling C. Johnson (a1) (a2) (a3)...

The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 “Decliners” and 101 “Stables”) enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9–8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed. (JINS, 2014, 20, 1–12)

Corresponding author
Correspondence and reprint requests to: Ozioma C. Okonkwo, Department of Medicine and Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792. E-mail:
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