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

Cynthia M Stonnington, Yinghua Chen, Cary R. Savage, Wendy Lee, Robert J. Bauer, Sameen Sharieff, Pradeep Thiyyagura, Gene E. Alexander, Richard John Caselli, Dona E Locke, Eric M. Reiman, Kewei Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)603-615
Number of pages13
JournalJournal of Alzheimer's Disease
Volume63
Issue number2
DOIs
StatePublished - Jan 1 2018

Fingerprint

Alzheimer Disease
Magnetic Resonance Imaging
Positron-Emission Tomography
Aptitude
Alleles
Apolipoprotein E4
Sex Education
Neuroimaging
ROC Curve
Cohort Studies
Logistic Models
Prospective Studies
Glucose
Sensitivity and Specificity
Control Groups
Brain
Cognitive Dysfunction

Keywords

  • Alzheimer's disease
  • magnetic resonance imaging
  • mild cognitive impairment
  • positron-emission tomography
  • prognosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Predicting Imminent Progression to Clinically Significant Memory Decline Using Volumetric MRI and FDG PET. / Stonnington, Cynthia M; Chen, Yinghua; Savage, Cary R.; Lee, Wendy; Bauer, Robert J.; Sharieff, Sameen; Thiyyagura, Pradeep; Alexander, Gene E.; Caselli, Richard John; Locke, Dona E; Reiman, Eric M.; Chen, Kewei.

In: Journal of Alzheimer's Disease, Vol. 63, No. 2, 01.01.2018, p. 603-615.

Research output: Contribution to journalArticle

Stonnington, CM, Chen, Y, Savage, CR, Lee, W, Bauer, RJ, Sharieff, S, Thiyyagura, P, Alexander, GE, Caselli, RJ, Locke, DE, Reiman, EM & Chen, K 2018, 'Predicting Imminent Progression to Clinically Significant Memory Decline Using Volumetric MRI and FDG PET', Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 603-615. https://doi.org/10.3233/JAD-170852
Stonnington, Cynthia M ; Chen, Yinghua ; Savage, Cary R. ; Lee, Wendy ; Bauer, Robert J. ; Sharieff, Sameen ; Thiyyagura, Pradeep ; Alexander, Gene E. ; Caselli, Richard John ; Locke, Dona E ; Reiman, Eric M. ; Chen, Kewei. / Predicting Imminent Progression to Clinically Significant Memory Decline Using Volumetric MRI and FDG PET. In: Journal of Alzheimer's Disease. 2018 ; Vol. 63, No. 2. pp. 603-615.
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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.",
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AU - Stonnington, Cynthia M

AU - Chen, Yinghua

AU - Savage, Cary R.

AU - Lee, Wendy

AU - Bauer, Robert J.

AU - Sharieff, Sameen

AU - Thiyyagura, Pradeep

AU - Alexander, Gene E.

AU - Caselli, Richard John

AU - Locke, Dona E

AU - Reiman, Eric M.

AU - Chen, Kewei

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N2 - 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.

AB - 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.

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KW - positron-emission tomography

KW - prognosis

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