White matter lesions defined by diffusion tensor imaging in older adults

Stephen Back, Christopher (Chris) Kroenke, Lawrence (Larry) Sherman, Gus Lawrence, Xi Gong, Erin N. Taber, Joshua A. Sonnen, Eric B. Larson, Thomas J. Montine

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Objective: The cellular and molecular mechanisms underlying magnetic resonance imaging-defined white matter (WM) changes associated with age-related cognitive decline remain poorly defined. We tested the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury. Methods: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population-based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation. Results: Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D. Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA. Interpretation: DTI-defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA-rich regions.

Original languageEnglish (US)
Pages (from-to)465-476
Number of pages12
JournalAnnals of Neurology
Volume70
Issue number3
DOIs
StatePublished - Sep 2011

Fingerprint

Cerebrovascular Trauma
Diffusion Tensor Imaging
Anisotropy
Oligodendroglia
Prefrontal Cortex
Free Radicals
Alzheimer Disease
Hyaluronic Acid
Wounds and Injuries
Docosahexaenoic Acids
Brain Diseases
Magnetic Fields
Myelin Sheath
White Matter
Autopsy
Biomarkers
Magnetic Resonance Imaging
Population

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

White matter lesions defined by diffusion tensor imaging in older adults. / Back, Stephen; Kroenke, Christopher (Chris); Sherman, Lawrence (Larry); Lawrence, Gus; Gong, Xi; Taber, Erin N.; Sonnen, Joshua A.; Larson, Eric B.; Montine, Thomas J.

In: Annals of Neurology, Vol. 70, No. 3, 09.2011, p. 465-476.

Research output: Contribution to journalArticle

Back, S, Kroenke, CC, Sherman, LL, Lawrence, G, Gong, X, Taber, EN, Sonnen, JA, Larson, EB & Montine, TJ 2011, 'White matter lesions defined by diffusion tensor imaging in older adults', Annals of Neurology, vol. 70, no. 3, pp. 465-476. https://doi.org/10.1002/ana.22484
Back, Stephen ; Kroenke, Christopher (Chris) ; Sherman, Lawrence (Larry) ; Lawrence, Gus ; Gong, Xi ; Taber, Erin N. ; Sonnen, Joshua A. ; Larson, Eric B. ; Montine, Thomas J. / White matter lesions defined by diffusion tensor imaging in older adults. In: Annals of Neurology. 2011 ; Vol. 70, No. 3. pp. 465-476.
@article{9c43369f34a441c89557288178599ad3,
title = "White matter lesions defined by diffusion tensor imaging in older adults",
abstract = "Objective: The cellular and molecular mechanisms underlying magnetic resonance imaging-defined white matter (WM) changes associated with age-related cognitive decline remain poorly defined. We tested the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury. Methods: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population-based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D∥) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation. Results: Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D∥. Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA. Interpretation: DTI-defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA-rich regions.",
author = "Stephen Back and Kroenke, {Christopher (Chris)} and Sherman, {Lawrence (Larry)} and Gus Lawrence and Xi Gong and Taber, {Erin N.} and Sonnen, {Joshua A.} and Larson, {Eric B.} and Montine, {Thomas J.}",
year = "2011",
month = "9",
doi = "10.1002/ana.22484",
language = "English (US)",
volume = "70",
pages = "465--476",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - White matter lesions defined by diffusion tensor imaging in older adults

AU - Back, Stephen

AU - Kroenke, Christopher (Chris)

AU - Sherman, Lawrence (Larry)

AU - Lawrence, Gus

AU - Gong, Xi

AU - Taber, Erin N.

AU - Sonnen, Joshua A.

AU - Larson, Eric B.

AU - Montine, Thomas J.

PY - 2011/9

Y1 - 2011/9

N2 - Objective: The cellular and molecular mechanisms underlying magnetic resonance imaging-defined white matter (WM) changes associated with age-related cognitive decline remain poorly defined. We tested the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury. Methods: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population-based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D∥) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation. Results: Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D∥. Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA. Interpretation: DTI-defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA-rich regions.

AB - Objective: The cellular and molecular mechanisms underlying magnetic resonance imaging-defined white matter (WM) changes associated with age-related cognitive decline remain poorly defined. We tested the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury. Methods: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population-based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D∥) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation. Results: Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D∥. Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA. Interpretation: DTI-defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA-rich regions.

UR - http://www.scopus.com/inward/record.url?scp=80052269275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052269275&partnerID=8YFLogxK

U2 - 10.1002/ana.22484

DO - 10.1002/ana.22484

M3 - Article

VL - 70

SP - 465

EP - 476

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -