Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome

James T Kennedy; Julie K Wisch; Aylin Dincer; June Roman; Brian A Gordon; Benjamin Handen; Tammie L S Benzinger; Elizabeth Head; Mark Mapstone; Bradley T Christian; Dana L Tudorascu; Charles L Laymon; Sigan L Hartley; Patrick Lao; Adam M Brickman; Shahid H Zaman; Beau M Ances; ABC‐DS and DIAN Consortia

doi:10.1002/alz.14519

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome

Alzheimers Dement. 2025 Jan 14:e14519. doi: 10.1002/alz.14519. Online ahead of print.

Authors

James T Kennedy¹, Julie K Wisch¹, Aylin Dincer², June Roman¹, Brian A Gordon^{2

3}, Benjamin Handen⁴, Tammie L S Benzinger², Elizabeth Head^{5

6}, Mark Mapstone⁷, Bradley T Christian^{8

9}, Dana L Tudorascu⁴, Charles L Laymon¹⁰, Sigan L Hartley^{8

11}, Patrick Lao^{12

13}, Adam M Brickman^{12

13}, Shahid H Zaman¹⁴, Beau M Ances¹; ABC‐DS and DIAN Consortia

Affiliations

¹ Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
² Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
³ Department of Psychological & Brain Sciences, Washington University, St. Louis, Missouri, USA.
⁴ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁵ Department of Pathology and Laboratory Medicine, University of California, Medical Sciences D, Irvine, California, USA.
⁶ Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
⁷ Department of Neurology, University of California, Irvine, California, USA.
⁸ Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁹ Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁰ Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹¹ Department of Human Development & Family Studies, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹² Department of Neurology, Columbia University, New York, New York, USA.
¹³ Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
¹⁴ Cambridge Intellectual and Developmental Disabilities Research Group, University of Cambridge, Cambridge, UK.

PMID: 39807622
DOI: 10.1002/alz.14519

Abstract

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic). Cortical thickness and subcortical volumes were compared between DS groups and evaluated as a staging metric using receiver operating characteristic analyses. Thickness patterns were compared to those previously reported in autosomal-dominant AD (ADAD).

Results: Decreased parietal and temporal lobe thickness differentiated amyloid positivity (area under the curve [AUC] = 0.83) and impairment (AUC = 0.81), and slightly outperformed subcortical volumes (AUC = 0.8/0.74). Thickness differences in DS were more widespread, severe, and had better discriminative ability than ADAD.

Discussion: Cortical thickness can stage AD pathology in DS. Identification of brain regions affected by AD may aid in tracking disease course and evaluating treatment effects.

Highlights: DSAD is associated with reduced temporal and parietal cortical thickness. DSAD is associated with smaller hippocampal and striatal volumes. Thickness differences can stage DSAD better than other forms of AD. DSAD thickness differences are more extensive and severe than ADAD.

Keywords: Alzheimer's; Down syndrome; MRI; amyloid; autosomal dominant Alzheimer's disease; cognitive impairment; cortical thickness; dementia; subcortical volume.

Abstract

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