Predicting Imminent Progression to Clinically Significant Memory Decline Using Volumetric MRI and FDG PET

Article type: Research Article

Authors: Stonnington, Cynthia M.^{a; j; *} | Chen, Yinghua^{b; j} | Savage, Cary R.^{b; j} | Lee, Wendy^{b; j} | Bauer III, Robert J.^{b; j} | Sharieff, Sameen^{a; c; j} | Thiyyagura, Pradeep^{b; j} | Alexander, Gene E.^{h; i; j} | Caselli, Richard J.^{d; j} | Locke, Dona E.C.^{a; j} | Reiman, Eric M.^{b; f; g; j} | Chen, Kewei^{b; e; g; j}

Affiliations: [a] Department of Psychiatry and Psychology, Mayo Clinic Arizona, Scottsdale, AZ, USA | [b] Banner Alzheimer’s Institute and Banner Good Samaritan PET Center, Phoenix, AZ, USA | [c] Midwestern University, Glendale, AZ, USA | [d] Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA | [e] Arizona State University, Tempe, AZ, USA | [f] Translational Genomics Research Institute, Scottsdale, AZ, USA | [g] Department of Psychiatry, University of Arizona, Tucson, AZ, USA | [h] Department of Psychology and Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA | [i] Neuroscience and Physiological Science Interdisciplinary Graduate Programs, University of Arizona, Tucson, AZ, USA | [j] Arizona Alzheimer’s Consortium, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Cynthia M. Stonnington, MD, Department of Psychiatry and Psychology, Mayo Clinic in Arizona, 13400 E Shea Blvd., Scottsdale, AZ 85259, USA. Tel.: +1 480 301 4853; Fax: +1 480 301 6258; E-mail: [email protected].

Abstract: Background:Brain imaging measurements can provide evidence of possible preclinical Alzheimer’s disease (AD). Their ability to predict individual imminent clinical conversion remains unclear. Objective:To investigate the ability of pre-specified volumetric magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) measurements to predict which cognitively unimpaired older participants would subsequently progress to amnestic mild cognitive impairment (aMCI) within 2 years. Methods:From an apolipoprotein E4 (APOE4) enriched prospective cohort study, 18 participants subsequently progressed to the clinical diagnosis of aMCI or probable AD dementia within 1.8±0.8 years (progressors); 20 participants matched for sex, age, education, and APOE allele dose remained cognitively unimpaired for at least 4 years (nonprogressors). A complementary control group not matched for APOE allele dose included 35 nonprogressors. Groups were compared on baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD and by voxel-wise differences in regional gray matter volume and glucose metabolism. Receiver Operating Characteristic, binary logistic regression, and leave-one-out procedures were used to predict clinical outcome for the a priori measures. Results:Compared to non-progressors and regardless of APOE-matching, progressors had significantly reduced baseline MRI and PET measurements in brain regions preferentially affected by AD and reduced hippocampal volume was the strongest predictor of an individual’s imminent progression to clinically significant memory decline (79% sensitivity/78% specificity among APOE-matched cohorts). Conclusion:Regional MRI and FDG-PET measurements may be useful in predicting imminent progression to clinically significant memory decline.

Keywords: Alzheimer’s disease, magnetic resonance imaging, mild cognitive impairment, positron-emission tomography, prognosis

DOI: 10.3233/JAD-170852

Journal: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 603-615, 2018