Widespread white matter degeneration preceding the onset of dementia

Klaus H Maier-Hein; Carl-Fredrik Westin; Martha E Shenton; Michael W Weiner; Ashish Raj; Philipp Thomann; Ron Kikinis; Bram Stieltjes; Ofer Pasternak

doi:10.1016/j.jalz.2014.04.518

Widespread white matter degeneration preceding the onset of dementia

Alzheimers Dement. 2015 May;11(5):485-493.e2. doi: 10.1016/j.jalz.2014.04.518. Epub 2014 Jul 14.

Authors

Klaus H Maier-Hein¹, Carl-Fredrik Westin², Martha E Shenton³, Michael W Weiner⁴, Ashish Raj⁵, Philipp Thomann⁶, Ron Kikinis², Bram Stieltjes⁷, Ofer Pasternak⁸

Affiliations

¹ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Junior Group Medical Image Computing, German Cancer Research Center, Heidelberg, Germany; Junior Group Quantitative Image-based Disease Characterization, German Cancer Research Center, Heidelberg, Germany. Electronic address: k.maier-hein@dkfz.de.
² Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Health Scientist, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA, USA.
⁴ Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, USA.
⁵ Image Data Evaluation and Analytics Lab (IDEAL), Weill Cornell Medical College, New York, NY, USA.
⁶ Department of General Psychiatry, Section of Geriatric Psychiatry, Ruprecht-Karls-University, Heidelberg, Germany.
⁷ Junior Group Quantitative Image-based Disease Characterization, German Cancer Research Center, Heidelberg, Germany.
⁸ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Background: Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer's disease (AD).

Methods: Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups.

Results: FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P < .05). The extent of increases was similar to that found comparing AD with controls.

Conclusion: Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.

Keywords: Alzheimer's disease; Diffusion tensor imaging; Free-water imaging; Mild cognitive impairment; Partial volume elimination.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Anisotropy
Cognitive Dysfunction / complications
Dementia / etiology*
Diffusion Tensor Imaging
Disease Progression
Female
Humans
Image Processing, Computer-Assisted
Male
Mental Status Schedule
Middle Aged
Nerve Degeneration / complications*
Nerve Degeneration / pathology
Nerve Fibers, Myelinated / pathology*
Neuropsychological Tests
White Matter / pathology*

Abstract

Publication types

MeSH terms

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