Dissociation of Down syndrome and Alzheimer's disease effects with imaging

Dawn C Matthews; Ana S Lukic; Randolph D Andrews; Boris Marendic; James Brewer; Robert A Rissman; Lisa Mosconi; Stephen C Strother; Miles N Wernick; William C Mobley; Seth Ness; Mark E Schmidt; Michael S Rafii

doi:10.1016/j.trci.2016.02.004

Dissociation of Down syndrome and Alzheimer's disease effects with imaging

Alzheimers Dement (N Y). 2016 Jun;2(2):69-81. doi: 10.1016/j.trci.2016.02.004.

Authors

Affiliations

¹ ADM Diagnostics, Northbrook, IL, USA.
² Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA, USA.
³ Department of Psychiatry, New York University Langone School of Medicine, New York, NY, USA.
⁴ Rotman Research Institute, Baycrest Hospital and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁵ Departments of Electrical and Computer Engineering and Biomedical Engineering, Medical Imaging Research Center, Illinois Institute of Technology, Chicago, IL, USA.
⁶ Janssen Research and Development LLC, Raritan, NJ, USA.
⁷ Janssen Pharmaceutica, Beerse, Belgium.

Abstract

Introduction: Down Syndrome (DS) adults experience accumulation of Alzheimer's disease (AD)-like amyloid plaques and tangles and a high incidence of dementia and could provide an enriched population to study AD-targeted treatments. However, to evaluate effects of therapeutic intervention, it is necessary to dissociate the contributions of DS and AD from overall phenotype. Imaging biomarkers offer the potential to characterize and stratify patients who will worsen clinically but have yielded mixed findings in DS subjects.

Methods: We evaluated 18F fluorodeoxyglucose positron emission tomography (PET), florbetapir PET, and structural magnetic resonance (sMR) image data from 12 nondemented DS adults using advanced multivariate machine learning methods.

Results: Our results showed distinctive patterns of glucose metabolism and brain volume enabling dissociation of DS and AD effects. AD-like pattern expression corresponded to amyloid burden and clinical measures.

Discussion: These findings lay groundwork to enable AD clinical trials with characterization and disease-specific tracking of DS adults.

Keywords: AV-45; Alzheimer’s; Amyloid; Biomarker initiative; Classifier; Clinical trials; DSBI; Down syndrome; FDG; Glucose metabolism; Imaging; MRI; NPAIRS; PET; Prodromal.

Abstract

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