Postmortem brain MRI is related to cognitive decline, independent of cerebral vessel disease in older adults.

Robert J Dawe, Lei Yu, Julie A Schneider, Konstantinos Arfanakis, David A Bennett, Patricia A Boyle
Author Information
  1. Robert J Dawe: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA. Electronic address: Robert_Dawe@rush.edu.
  2. Lei Yu: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  3. Julie A Schneider: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
  4. Konstantinos Arfanakis: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
  5. David A Bennett: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  6. Patricia A Boyle: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.

Abstract

The purpose of this study was to determine whether metrics of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late-life cognitive decline, independent of cerebral vessel disease. Using data from 554 older adults, we used voxelwise regression to identify regions where the postmortem MRI transverse relaxation rate constant R was associated with the rate of decline in global cognition. We then used linear mixed models to investigate the association between a composite R measure and cognitive decline, controlling for neuropathology including 3 indices of vessel disease: atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. This composite R measure was associated with the rate of decline (0.049 unit annually per R unit, p < 0.0001) and accounted for 6.1% of its variance, beyond contributions from vessel disease indices and other prominent age-related neuropathologies. Thus, postmortem brain R reflects disease processes underlying cognitive decline that are not captured by vessel disease indices or other standard neuropathologic indices and may provide a measure of brain tissue integrity that is complementary to histopathologic evaluation.

Keywords

References

  1. Sleep Breath. 2017 Sep;21(3):703-711 [PMID: 28271327]
  2. J Neurosci. 1997 Oct 1;17(19):7267-77 [PMID: 9295373]
  3. Psychiatry Res. 2013 Dec 30;214(3):389-94 [PMID: 24144509]
  4. Ann Neurol. 2011 Feb;69(2):320-7 [PMID: 21387377]
  5. Cerebrovasc Dis. 2002;14(2):109-15 [PMID: 12187015]
  6. J Cereb Blood Flow Metab. 2016 Jan;36(1):132-42 [PMID: 26036933]
  7. Psychiatry Res. 2009 May 15;172(2):117-20 [PMID: 19324534]
  8. Neurology. 2013 Sep 10;81(11):977-83 [PMID: 23935177]
  9. Mult Scler. 2006 Dec;12(6):747-53 [PMID: 17263002]
  10. Ann Neurol. 2015 Jun;77(6):942-52 [PMID: 25707479]
  11. Ann Neurol. 2013 Apr;73(4):529-36 [PMID: 23424091]
  12. Neurobiol Aging. 2014 Jul;35(7):1549-61 [PMID: 24582637]
  13. Sleep. 2008 Jul;31(7):967-77 [PMID: 18652092]
  14. J Cereb Blood Flow Metab. 2016 Jan;36(1):40-54 [PMID: 25944592]
  15. Ann Neurol. 2007 May;61(5):403-10 [PMID: 17328068]
  16. Ann Neurol. 2013 Sep;74(3):478-89 [PMID: 23798485]
  17. Alzheimers Dement. 2012 Oct;8(5 Suppl):S104-11 [PMID: 22537801]
  18. J Am Geriatr Soc. 2013 Mar;61(3):396-402 [PMID: 23414481]
  19. Lancet Neurol. 2016 Aug;15(9):934-943 [PMID: 27312738]
  20. Front Hum Neurosci. 2013 Nov 18;7:782 [PMID: 24302906]
  21. Curr Alzheimer Res. 2012 Jul;9(6):628-45 [PMID: 22471860]
  22. Lancet Neurol. 2011 Sep;10(9):829-43 [PMID: 21778116]
  23. J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):126-35 [PMID: 20935330]
  24. J Nucl Med. 2009 Dec;50(12):1969-74 [PMID: 19910418]
  25. Acta Neuropathol. 2009 Jul;118(1):87-102 [PMID: 19234858]
  26. Curr Alzheimer Res. 2012 Jul;9(6):646-63 [PMID: 22471867]
  27. Neurology. 2015 Dec 1;85(22):1930-6 [PMID: 26537052]
  28. Nat Rev Neurol. 2015 Mar;11(3):157-65 [PMID: 25686760]
  29. Biochim Biophys Acta. 2016 May;1862(5):926-38 [PMID: 26687324]
  30. Lancet Neurol. 2002 Nov;1(7):426-36 [PMID: 12849365]
  31. Neurology. 2010 Sep 21;75(12):1070-8 [PMID: 20844243]
  32. J Cereb Blood Flow Metab. 2013 Aug;33(8):1168-72 [PMID: 23652626]
  33. Psychol Aging. 2015 Mar;30(1):74-82 [PMID: 25664558]
  34. Stroke. 1996 Sep;27(9):1641-6; discussion 1647 [PMID: 8784142]
  35. Neurol Res. 2004 Jul;26(5):525-39 [PMID: 15265270]
  36. Stroke. 2008 Apr;39(4):1127-33 [PMID: 18292383]
  37. J Neuropathol Exp Neurol. 2011 Nov;70(11):960-9 [PMID: 22002422]
  38. Age Ageing. 2011 Nov;40(6):684-9 [PMID: 21890481]
  39. J Neuropathol Exp Neurol. 2003 Dec;62(12):1287-301 [PMID: 14692704]
  40. Stroke. 2006 Jul;37(7):1759-64 [PMID: 16763176]
  41. J Neurochem. 2018 Mar;144(5):651-658 [PMID: 28833176]
  42. Stroke. 2004 Nov;35(11 Suppl 1):2616-9 [PMID: 15459438]
  43. Congest Heart Fail. 2013 Jul-Aug;19(4):E29-34 [PMID: 23517434]
  44. Neurobiol Aging. 2016 Sep;45:169-177 [PMID: 27459937]
  45. Int J Cardiol. 2016 Nov 15;223:681-687 [PMID: 27568989]
  46. Can J Cardiol. 2017 Dec;33(12):1587-1596 [PMID: 28966021]
  47. J Neurosci. 2002 Jan 15;22(2):455-63 [PMID: 11784790]

Grants

  1. UH3 NS100599/NINDS NIH HHS
  2. UH2 NS100599/NINDS NIH HHS
  3. R01 AG017917/NIA NIH HHS
  4. R01 AG033678/NIA NIH HHS
  5. P30 AG010161/NIA NIH HHS
  6. R01 AG034374/NIA NIH HHS
  7. UF1 NS100599/NINDS NIH HHS
  8. R01 AG015819/NIA NIH HHS

MeSH Term

Aged
Aged, 80 and over
Autopsy
Brain
Cerebral Amyloid Angiopathy
Cognitive Dysfunction
Female
Humans
Intracranial Arteriosclerosis
Magnetic Resonance Imaging
Male
Neuropathology

Word Cloud

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