Sensitivity of restriction spectrum imaging to memory and neuropathology in Alzheimer’s disease
Open accessAbstract
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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CI demonstrated widespread microstructural abnormalities compared to CN, with the strongest differences in entorhinal cortex IF and HI, and hippocampal RI; CI showed higher IF, and lower RI and HI, than CN.
“As we previously reported in an overlapping sample [25], CI demonstrated widespread microstructural abnormalilties compared to CN (Additional file 1: Figure S2A), with the strongest differences in entorhinal cortex IF and HI, and hippocampal RI (p < 0.001); CI showed higher IF, and lower RI and HI, than CN.”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [25]
The Results section (page unavailable) reports lower neurite density (ND) across white matter in MCI and AD than in healthy controls, and higher entorhinal cortex isotropic free-water diffusion (IF). It does not report the claimed entorhinal HI or hippocampal RI differences, nor establish those measures as the strongest group differences; the paper analyzes ND and IF rather than RI and HI. (LLM, conf=0.86)
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Reas, E. T., Triebswetter, C., Banks, S. J., & McEvoy, L. K. (2024) · Alzheimer's Research & Therapy · doi:10.1186/s13195-023-01380-w · Cited by 20 · see citing works
“However, widespread WM differences by cognitive status were observed, consistent with our prior findings in an overlapping sample [25], that were not modified by APOE4 .”
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- Authors
- Reas, E. T., Hagler, D. J., White, N. S., Kuperman, J. M., Bartsch, H., Cross, K., Loi, R. Q., Balachandra, A. R., Meloy, M. J., Wierenga, C. E., Galasko, D., Brewer, J. B., Dale, A. M., & McEvoy, L. K.
- Affiliations
- University of California San Diego (US)
- Wayne State University (US)
- Corresponding author
- Reas, Emilie T.
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2017-08-02
- Volume
- 9
- Issue
- 1
- Pages
- 55-55
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC5539622
- OpenAlex
- W2741829806
- Cited by
- 35
- References
- 61
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- BrightFocus Foundation (A2016241F)
- National Institute on Aging (5P50AG005131)
- U.S. Department of Veterans Affairs (5I01CX000565)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- restriction spectrum imaging, Alzheimer's disease, mild cognitive impairment, episodic memory, neurite density, amyloid-beta, arcuate fasciculus, entorhinal cortex, hippocampus, diffusion MRI, diffusion tensor imaging, fractional anisotropy, mean diffusivity, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Image Processing, Computer-Assisted, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Peptide Fragments, Psychiatric Status Rating Scales, Amyloid beta-Peptides, Anisotropy, Diffusion Tensor Imaging
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