H Diana Rosas1,2, Eugene Hsu1,2, Nathaniel D Mercaldo1, Florence Lai1, Margaret Pulsifer1, David Keator3, Adam M Brickman4,5, Julie Price2, Michael Yassa6, Christy Hom3, Sharon J Krinsky-McHale7, Wayne Silverman8,9, Ira Lott9, Nicole Schupf4,5,10. 1. Department of Neurology Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA. 2. Department of Radiology Athinoula Martinos Center Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts USA. 3. Department of Psychiatry and Human Behavior University of California Irvine California USA. 4. G. H. Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain College of Physicians and Surgeons Columbia University New York New York USA. 5. Department of Neurology College of Physicians and Surgeons Columbia University New York New York USA. 6. Department of Neurobiology and Behavior University of California California, USA Irvine. 7. New York Institute for Basic Research in Developmental Disabilities New York New York USA. 8. Kennedy Krieger Institute Johns Hopkins University School of Medicine, Baltimore Maryland USA. 9. Department of Pediatrics Irvine Medical Center University of California Irvine California USA. 10. Department of Epidemiology Mailman School of Public Health Columbia University New York New York USA.
Abstract
INTRODUCTION: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD)-associated neuropathology by the age of 40, with risk for dementia increasing from the early 50s. White matter (WM) pathology has been reported in sporadic AD, including early demyelination, microglial activation, loss of oligodendrocytes and reactive astrocytes but has not been extensively studied in the at-risk DS population. METHODS: Fifty-six adults with DS (35 cognitively stable adults, 11 with mild cognitive impairment, 10 with dementia) underwent diffusion-weighted magnetic resonance imaging (MRI), amyloid imaging, and had assessments of cognition and functional abilities using tasks appropriate for persons with intellectual disability. RESULTS: Early changes in late-myelinating and relative sparing of early-myelinating pathways, consistent with the retrogenesis model proposed for sporadic AD, were associated with AD-related cognitive deficits and with regional amyloid deposition. DISCUSSION: Our findings suggest that quantification of WM changes in DS could provide a promising and clinically relevant biomarker for AD clinical onset and progression.
INTRODUCTION: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD)-associated neuropathology by the age of 40, with risk for dementia increasing from the early 50s. White matter (WM) pathology has been reported in sporadic AD, including early demyelination, microglial activation, loss of oligodendrocytes and reactive astrocytes but has not been extensively studied in the at-risk DS population. METHODS: Fifty-six adults with DS (35 cognitively stable adults, 11 with mild cognitive impairment, 10 with dementia) underwent diffusion-weighted magnetic resonance imaging (MRI), amyloid imaging, and had assessments of cognition and functional abilities using tasks appropriate for persons with intellectual disability. RESULTS: Early changes in late-myelinating and relative sparing of early-myelinating pathways, consistent with the retrogenesis model proposed for sporadic AD, were associated with AD-related cognitive deficits and with regional amyloid deposition. DISCUSSION: Our findings suggest that quantification of WM changes in DS could provide a promising and clinically relevant biomarker for AD clinical onset and progression.
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