4.1 Article

MRI assessment of whole-brain structural changes in aging

Journal

CLINICAL INTERVENTIONS IN AGING
Volume 12, Issue -, Pages 1251-1270

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/CIA.S139515

Keywords

aging; brain atrophy and lesion index (BALI); brain health; MRI pulse sequences; structural brain changes

Funding

  1. Canadian Institutes of Health Research [CSE125739]
  2. National Nature Science Foundation of China [81401379]
  3. Surrey Hospital & Outpatient Centre Foundation
  4. Dalhousie Medical Research Foundation as Kathryn Allen Weldon Chair in Alzheimer Research
  5. ADNI (National Institutes of Health [NIH] Grant) [U01 AG024904]
  6. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  7. National Institute on Aging (NIA)
  8. National Institute of Biomedical Imaging and Bioengineering
  9. AbbVie
  10. Alzheimer's Association
  11. Alzheimer's Drug Discovery Foundation
  12. Araclon Biotech
  13. BioClinica, Inc.
  14. Biogen
  15. Bristol-Myers Squibb Company
  16. CereSpir, Inc.
  17. Cogstate
  18. Eisai Inc.
  19. Elan Pharmaceuticals, Inc.
  20. Eli Lilly and Company
  21. EuroImmun
  22. F Hoffmann-La Roche Ltd
  23. Genentech, Inc.
  24. Fujirebio
  25. GE Healthcare
  26. IXICO Ltd.
  27. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  28. Johnson & Johnson Phar-maceutical Research & Development LLC.
  29. Lumosity
  30. Lundbeck
  31. Merck Co., Inc.
  32. Meso Scale Diagnostics, LLC.
  33. NeuroRx Research
  34. Neurotrack Technologies
  35. Novartis Pharmaceuticals Corporation
  36. Pfizer Inc.
  37. Piramal Imaging
  38. Servier
  39. Takeda Pharmaceutical Company
  40. Transition Therapeutics
  41. Canadian Institutes of Health Research
  42. NIA/NIH [U01 AG016976]
  43. NIA [P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134]
  44. [P50 AG005131]
  45. [P50 AG023501]
  46. [P30 AG035982]
  47. [P30 AG028383]
  48. [P30 AG010124]
  49. [P50 AG005133]
  50. [P50 AG005142]
  51. [P30 AG012300]
  52. [P50 AG005136]
  53. [P50 AG033514]
  54. [P50 AG005681]
  55. [P50 AG047270]
  56. [P50 AG016574]
  57. [P50 AG005138]
  58. [P30 AG008051]
  59. [P30 AG013854]
  60. [P30 AG008017]
  61. [P30 AG010161]
  62. [P50 AG047366]
  63. [P30 AG010129]
  64. [P50 AG016573]
  65. [P50 AG016570]

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Purpose: One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Materials and methods: Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n = 950; women = 47.9%; age = 72.7 +/- 7.4 years); the National Alzheimer's Coordinating Center (n = 722; women = 55.1%; age = 72.7 +/- 9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n = 170; women =60.0%; age =62.9 +/- 9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2* GRE) images. Results: Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r(2)>0.69; P<0.00001). They were associated with age (r(2)>0.29; P<0.00001) and differed by cognitive status (chi(2)>26.48, P<0.00001). T2-FLAIR revealed a greater level of periventricular (chi(2)=29.09) and deep white matter (chi(2) = 26.65, P<0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI (P<0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2* GRE. Conclusion: The T1WI-and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

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