Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?

Topic: Amyloid, tau and blood-test diagnosis

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.

Key findings

• 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.

Why it matters

In 56 adults with Down syndrome, early changes in white matter were associated with Alzheimer-related cognitive deficits and with regional amyloid deposition. The authors suggest that measuring white matter changes could be a promising biomarker for onset and progression, but this is not a treatment or cure.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1002/dad2.12040
• PubMed: 33204811
• Original source →
• Free full text: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{rosas2020-33204811,
  author  = {Rosas, H. D. and Hsu, E. and Mercaldo, N. D. and Lai, F. and Pulsifer, M. and Keator, D. and Brickman, A. M. and Price, J. and others},
  title   = {{Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?}},
  journal = {Alzheimer's \& dementia (Amsterdam, Netherlands)},
  year    = {2020},
  doi     = {10.1002/dad2.12040},
  pmid    = {33204811},
  url     = {https://doi.org/10.1002/dad2.12040}
}

Studies this one cites

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• Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing Journal of the Royal Statistical Society Series B (Statistical Methodology) · 1995-01-01 · usefulness score 52/100 · Laboratory science
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• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is

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