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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Sensitivity of restriction spectrum imaging to memory and neuropathology in Alzheimer’s disease

Authors: Emilie T. Reas, Donald J. Hagler Jr, Nathan S. White, Joshua M. Kuperman, Hauke Bartsch, Karalani Cross, Richard Q. Loi, Akshara R. Balachandra, M. J. Meloy, Christina E. Wierenga, Douglas Galasko, James B. Brewer, Anders M. Dale, Linda K. McEvoy

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

Diffusion imaging has demonstrated sensitivity to structural brain changes in Alzheimer’s disease (AD). However, there remains a need for a more complete characterization of microstructural alterations occurring at the earliest disease stages, and how these changes relate to underlying neuropathology. This study evaluated the sensitivity of restriction spectrum imaging (RSI), an advanced diffusion magnetic resonance imaging (MRI) technique, to microstructural brain changes in mild cognitive impairment (MCI) and AD.

Methods

MRI and neuropsychological test data were acquired from 31 healthy controls, 12 individuals with MCI, and 13 individuals with mild AD, aged 63–93 years. Cerebrospinal fluid amyloid-β levels were measured in a subset (n = 38) of participants. RSI measures of neurite density (ND) and isotropic free water (IF) were computed in fiber tracts and in hippocampal and entorhinal cortex gray matter, respectively. Analyses evaluated whether these measures predicted memory performance, correlated with amyloid-β levels, and distinguished impaired individuals from controls. For comparison, analyses were repeated with standard diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity.

Results

Both RSI and DTI measures correlated with episodic memory and disease severity. RSI, but not DTI, measures correlated with amyloid-β42 levels. ND and FA in the arcuate fasciculus and entorhinal cortex IF most strongly predicted recall performance. RSI measures of arcuate fasciculus ND and entorhinal cortex IF best discriminated memory impaired participants from healthy participants.

Conclusions

RSI is highly sensitive to microstructural changes in the early stages of AD, and is associated with biochemical markers of AD pathology. Reduced ND in cortical association fibers and increased medial temporal lobe free-water diffusion predicted episodic memory, distinguished cognitively impaired from healthy individuals, and correlated with amyloid-β. Although further research is needed to assess the sensitivity of RSI to preclinical AD and disease progression, these results suggest that RSI may be a promising tool to better understand neuroanatomical changes in AD and their association with neuropathology.
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Metadata
Title
Sensitivity of restriction spectrum imaging to memory and neuropathology in Alzheimer’s disease
Authors
Emilie T. Reas
Donald J. Hagler Jr
Nathan S. White
Joshua M. Kuperman
Hauke Bartsch
Karalani Cross
Richard Q. Loi
Akshara R. Balachandra
M. J. Meloy
Christina E. Wierenga
Douglas Galasko
James B. Brewer
Anders M. Dale
Linda K. McEvoy
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0281-7

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