Open AccessAlzheimer‐related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?
Author(s) -
Rosas H. Diana,
Hsu Eugene,
Mercaldo Nathaniel D.,
Lai Florence,
Pulsifer Margaret,
Keator David,
Brickman Adam M.,
Price Julie,
Yassa Michael,
Hom Christy,
KrinskyMcHale Sharon J.,
Silverman Wayne,
Lott Ira,
Schupf Nicole
Publication year - 2020
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12040
Subject(s) - neuropathology , white matter , dementia , biomarker , magnetic resonance imaging , cognitive decline , alzheimer's disease , psychology , diffusion mri , medicine , neuroscience , amyloid (mycology) , pathology , disease , biology , radiology , biochemistry
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.