Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2024 May 17

PMID 38759008

Authors

Moto Nakaya

Noriko Sato

Hiroshi Matsuda

Norihide Maikusa

Miho Ota

Yoko Shigemoto

Daichi Sone

Tensho Yamao

Yukio Kimura

Tadashi Tsukamoto

Yuma Yokoi

Masuhiro Sakata

Osamu Abe

Affiliations

Soon will be listed here.

Abstract

Background: Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics.

Objective: The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics.

Methods: Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics.

Results: Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology.

Conclusions: This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

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References

Huang H, Zheng S, Yang Z, Wu Y, Li Y, Qiu J . Voxel-based morphometry and a deep learning model for the diagnosis of early Alzheimer's disease based on cerebral gray matter changes. Cereb Cortex. 2022; 33(3):754-763. PMC: 9890469. DOI: 10.1093/cercor/bhac099. View

Amlien I, Fjell A . Diffusion tensor imaging of white matter degeneration in Alzheimer's disease and mild cognitive impairment. Neuroscience. 2014; 276:206-15. DOI: 10.1016/j.neuroscience.2014.02.017. View

Jack Jr C, Holtzman D . Biomarker modeling of Alzheimer's disease. Neuron. 2013; 80(6):1347-58. PMC: 3928967. DOI: 10.1016/j.neuron.2013.12.003. View

Amadoru S, Dore V, McLean C, Hinton F, Shepherd C, Halliday G . Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease. Alzheimers Res Ther. 2020; 12(1):22. PMC: 7057642. DOI: 10.1186/s13195-020-00587-5. View

Armstrong R . Plaques and tangles and the pathogenesis of Alzheimer's disease. Folia Neuropathol. 2006; 44(1):1-11. View

Ji F, Pasternak O, Ng K, Chong J, Liu S, Zhang L . White matter microstructural abnormalities and default network degeneration are associated with early memory deficit in Alzheimer's disease continuum. Sci Rep. 2019; 9(1):4749. PMC: 6426923. DOI: 10.1038/s41598-019-41363-2. View

Ofori E, DeKosky S, Febo M, Colon-Perez L, Chakrabarty P, Duara R . Free-water imaging of the hippocampus is a sensitive marker of Alzheimer's disease. Neuroimage Clin. 2019; 24:101985. PMC: 6722298. DOI: 10.1016/j.nicl.2019.101985. View

Snow W, Dale R, OBrien-Moran Z, Buist R, Peirson D, Martin M . In Vivo Detection of Gray Matter Neuropathology in the 3xTg Mouse Model of Alzheimer's Disease with Diffusion Tensor Imaging. J Alzheimers Dis. 2017; 58(3):841-853. PMC: 5467717. DOI: 10.3233/JAD-170136. View

Blennow K, de Leon M, Zetterberg H . Alzheimer's disease. Lancet. 2006; 368(9533):387-403. DOI: 10.1016/S0140-6736(06)69113-7. View

10.

Silva-Rudberg J, Salardini E, ODell R, Chen M, Ra J, Georgelos J . Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. Am J Geriatr Psychiatry. 2023; 32(1):17-28. PMC: 10840732. DOI: 10.1016/j.jagp.2023.08.002. View

11.

Maillard P, Fletcher E, Singh B, Martinez O, Johnson D, Olichney J . Cerebral white matter free water: A sensitive biomarker of cognition and function. Neurology. 2019; 92(19):e2221-e2231. PMC: 6537135. DOI: 10.1212/WNL.0000000000007449. View

12.

Shiino A, Watanabe T, Maeda K, Kotani E, Akiguchi I, Matsuda M . Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and a unique pattern for early onset disease. Neuroimage. 2006; 33(1):17-26. DOI: 10.1016/j.neuroimage.2006.06.010. View

13.

Song S, Sun S, Ramsbottom M, Chang C, Russell J, Cross A . Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage. 2002; 17(3):1429-36. DOI: 10.1006/nimg.2002.1267. View

14.

Josephs K, Whitwell J, Duffy J, Vanvoorst W, Strand E, Hu W . Progressive aphasia secondary to Alzheimer disease vs FTLD pathology. Neurology. 2008; 70(1):25-34. PMC: 2749307. DOI: 10.1212/01.wnl.0000287073.12737.35. View

15.

Torso M, Ridgway G, Valotti M, Hardingham I, Chance S . In vivo cortical diffusion imaging relates to Alzheimer's disease neuropathology. Alzheimers Res Ther. 2023; 15(1):165. PMC: 10548768. DOI: 10.1186/s13195-023-01309-3. View

16.

Alexander A, Lee J, Lazar M, Field A . Diffusion tensor imaging of the brain. Neurotherapeutics. 2007; 4(3):316-29. PMC: 2041910. DOI: 10.1016/j.nurt.2007.05.011. View

17.

Burton E, McKeith I, Burn D, Williams E, OBrien J . Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. Brain. 2004; 127(Pt 4):791-800. DOI: 10.1093/brain/awh088. View

18.

Wang W, Chen R, Mayrand R, Adjouadi M, Fang R, DeKosky S . Association of longitudinal cognitive decline with diffusion MRI in Gray Matter, Amyloid, and Tau deposition. Neurobiol Aging. 2022; 121:166-178. DOI: 10.1016/j.neurobiolaging.2022.10.013. View

19.

Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y . Free water elimination and mapping from diffusion MRI. Magn Reson Med. 2009; 62(3):717-30. DOI: 10.1002/mrm.22055. View

20.

Henf J, Grothe M, Brueggen K, Teipel S, Dyrba M . Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction. Neuroimage Clin. 2017; 17:579-586. PMC: 5702878. DOI: 10.1016/j.nicl.2017.10.005. View