PET staging of amyloidosis using striatum

Bernard J Hanseeuw; Rebecca A Betensky; Elizabeth C Mormino; Aaron P Schultz; Jorge Sepulcre; John A Becker; Heidi I L Jacobs; Rachel F Buckley; Molly R LaPoint; Patrizia Vannini; Nancy J Donovan; Jasmeer P Chhatwal; Gad A Marshall; Kathryn V Papp; Rebecca E Amariglio; Dorene M Rentz; Reisa A Sperling; Keith A Johnson; Alzheimer's Disease Neuroimaging Initiative; Harvard Aging Brain Study

doi:10.1016/j.jalz.2018.04.011

PET staging of amyloidosis using striatum

Alzheimers Dement. 2018 Oct;14(10):1281-1292. doi: 10.1016/j.jalz.2018.04.011. Epub 2018 May 21.

Authors

Bernard J Hanseeuw¹, Rebecca A Betensky², Elizabeth C Mormino³, Aaron P Schultz³, Jorge Sepulcre⁴, John A Becker⁴, Heidi I L Jacobs⁵, Rachel F Buckley³, Molly R LaPoint³, Patrizia Vannini⁶, Nancy J Donovan⁷, Jasmeer P Chhatwal³, Gad A Marshall⁷, Kathryn V Papp⁷, Rebecca E Amariglio⁷, Dorene M Rentz⁷, Reisa A Sperling⁷, Keith A Johnson⁸; Alzheimer's Disease Neuroimaging Initiative; Harvard Aging Brain Study

Affiliations

¹ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neurosciences, Université Catholique de Louvain, Brussels, Belgium; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: bhanseeuw@mgh.harvard.edu.
² Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA, USA.
⁵ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
⁶ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Introduction: Amyloid positron emission tomography (PET) data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures.

Methods: We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition.

Results: Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid.

Discussion: PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research.

Keywords: Alzheimer's disease; Amyloid PET imaging; Classification; Cognitive aging; Cortex; MCI; Staging; Striatum; Structural MRI.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / genetics
Alzheimer Disease / metabolism
Amyloid beta-Peptides / metabolism
Amyloidosis / diagnostic imaging*
Amyloidosis / genetics
Amyloidosis / metabolism
Apolipoprotein E4 / genetics
Brain Concussion / diagnostic imaging
Brain Concussion / metabolism
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / genetics
Cognitive Dysfunction / metabolism
Corpus Striatum / diagnostic imaging*
Corpus Striatum / metabolism
Disease Progression
Female
Follow-Up Studies
Humans
Image Interpretation, Computer-Assisted
Longitudinal Studies
Male
Positron-Emission Tomography*
Prospective Studies
Severity of Illness Index

Substances

Amyloid beta-Peptides
Apolipoprotein E4

Abstract

Publication types

MeSH terms

Substances

Grants and funding