Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;99(4):1441-1453.
doi: 10.3233/JAD-231416.

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

Moto Nakaya  1   2 , Noriko Sato  1 , Hiroshi Matsuda  1   3 , Norihide Maikusa  1 , Miho Ota  1   4 , Yoko Shigemoto  1 , Daichi Sone  5   6 , Tensho Yamao  7 , Yukio Kimura  1 , Tadashi Tsukamoto  8 , Yuma Yokoi  9 , Masuhiro Sakata  10 , Osamu Abe  2
Affiliations

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

Moto Nakaya et al. J Alzheimers Dis. 2024.

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.

Keywords: 11C-Pittsburgh compound B PET; Alzheimer’s disease; diffusion tensor imaging; free water imaging; gray matter-based spatial statistics; voxel-based morphometry.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Comparison of the patients in the Alzheimer’s spectrum group (AD-S) with healthy controls. Voxel-based morphometry analysis showed gray matter volume loss in the hippocampus of patients in the AD-S group compared to that in the control group (p < 0.001; uncorrected). Blue-light blue voxels represent lower values.
Fig. 2
Fig. 2
Comparison of the patients in the Alzheimer’s disease-spectrum group (AD-S) with healthy controls (HCs). AD-S patients showed significantly higher free water (FW), mean diffusivity (MD), and radial diffusivity (RD) values than did HCs in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum. Red-yellow represents higher values. The skeleton is represented in green.
Fig. 3
Fig. 3
Relationship between Montreal Cognitive Assessment (MoCA) and FW metrics of patients in the Alzheimer’s disease-spectrum group (AD-S). AD-S patients showed significant negative correlations in the limbic areas, precuneus, frontal lobe, and temporal lobe. Blue-light blue voxels represent lower values. The skeleton is represented in green.
Fig. 4
Fig. 4
Relationship between Mini-Mental State Examination (MMSE) and FW metrics of patients in the Alzheimer’s disease-spectrum group (AD-S). AD-S patients showed significant negative correlations in the limbic areas, precuneus, frontal lobe, and temporal lobe. Blue-light blue voxels represent lower values. The skeleton is represented in green.
Fig. 5
Fig. 5
Relationship between Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and FW metrics of patients in the Alzheimer’s disease-spectrum group (AD-S). AD-S patients showed significant positive correlations in the limbic areas, precuneus, frontal lobe, and temporal lobe. Red-yellow represents higher values. The skeleton is represented in green.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Whitwell JL, Przybelski SA, Weigand SD, Knopman DS, Boeve BF, Petersen RC, Jack CR Jr (2007) 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer’s disease. Brain 130, 1777–1786. - PMC - PubMed
    1. de Toledo-Morrell L, Goncharova I, Dickerson B, Wilson RS, Bennett DA (2000) From healthy aging to early Alzheimer’s disease: In vivo detection of entorhinal cortex atrophy. Ann N Y Acad Sci 911, 240–253. - PubMed
    1. Wang L, Benzinger TL, Su Y, Christensen J, Friedrichsen K, Aldea P, McConathy J, Cairns NJ, Fagan AM, Morris JC, Ances BM (2016) Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between β-amyloid and tauopathy. JAMA Neurol 73, 1070–1077. - PMC - PubMed
    1. Pascoal TA, Mathotaarachchi S, Mohades S, Benedet AL, Chung C-O, Shin M, Wang S, Beaudry T, Kang MS, Soucy J-P, Labbe A, Gauthier S, Rosa-Neto P (2017) Amyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer’s disease. Mol Psychiatry 22, 306–311. - PMC - PubMed
    1. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL, Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol 12, 357–367. - PubMed

MeSH terms