Journal of the International Neuropsychological Society

Research Articles

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

Ozioma C. Okonkwoa1a2a3 c1, Jennifer M. Oha1a2, Rebecca Koscika3, Erin Jonaitisa3, Caitlin A. Clearya1a2, N. Maritza Dowlinga2a4, Barbara B. Bendlina1a2a3, Asenath LaRuea3, Bruce P. Hermanna2a3a5, Todd E. Barnharta6, Dhanabalan Muralia6, Howard A. Rowleya2a7, Cynthia M. Carlssona1a2a3, Catherine L. Gallaghera1a2a5, Sanjay Asthanaa1a2a3, Mark A. Sagera2a3, Brad T. Christiana2a6 and Sterling C. Johnsona1a2a3

a1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

a2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

a3 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

a4 Department of Biostatistics & Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

a5 Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

a6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

a7 Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Abstract

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)

(Received July 05 2013)

(Revised January 17 2014)

(Accepted January 21 2014)

(Online publication March 11 2014)

Keywords

  • Longitudinal cognitive decline;
  • Amyloid;
  • FDG;
  • fMRI;
  • Family history of AD;
  • Preclinical AD

Correspondence

c1 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: ozioma@medicine.wisc.edu.