Cited by 288Dementia and Cognitive Impairment ResearchAdvanced Neuroimaging Techniques and ApplicationsAlzheimer's disease research and treatments

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White Matter Damage in Alzheimer Disease and Its Relationship to Gray Matter Atrophy

Agosta, Federica, Pievani, Michela, Sala, Stefania, Geroldi, Cristina, Galluzzi, Samantha, Frisoni, Giovanni B., Filippi, Massimo·2011·Radiology

DOI 10.1148/radiol.10101284

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Abstract

PURPOSE: To explore the regional patterns of white matter (WM) tract damage in (a) patients with probable Alzheimer disease (AD) and (b) patients with amnestic mild cognitive impairment (aMCI) and at least one abnormal biomarker and to investigate whether WM damage is related to gray matter (GM) atrophy. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained from each participant. Twenty-three patients with AD, 15 patients with aMCI, and 15 healthy control subjects underwent diffusion tensor magnetic resonance imaging. WM tract damage was investigated by using tract-based spatial statistics, and GM atrophy was measured by using voxel-based morphometry. RESULTS: Compared with control subjects, patients with AD had an increase in mean diffusivity in all major WM tracts studied, including the limbic, cortico-cortical, interhemispheric, and corticospinal tracts. Conversely, fractional anisotropy decreased only in the parahippocampal tract, fornix, and small, inferior parietal regions. In addition, patients with AD showed a widespread increase in axial and radial diffusivity compared with control subjects. Patients with aMCI showed an increase in axial diffusivity only in tracts projecting to the frontal cortex and splenium of the corpus callosum. Significant and anatomically congruent correlations between WM changes and regional GM atrophy were found in patients with AD. Conversely, damage to most WM tracts in patients with aMCI did not correlate with GM atrophy. CONCLUSION: In AD, the observed patterns of WM abnormalities may reflect the advanced phase of a secondary degenerative process and an association, especially in the early phases of the disease, with primary WM tract damage over and above GM abnormalities.

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Authors: Agosta, F., Pievani, M., Sala, S., Geroldi, C., Galluzzi, S., Frisoni, G. B., & Filippi, M.
Affiliations: IRCCS Ospedale San Raffaele (IT)
Centro San Giovanni di Dio Fatebenefratelli (IT)
Vita-Salute San Raffaele University (IT)
ORCID: Agosta, Federica
Pievani, Michela
Geroldi, Cristina
Galluzzi, Samantha
Frisoni, Giovanni B.
Filippi, Massimo
Venue: Radiology
Publisher: Radiological Society of North America (RSNA)
Published: 2011-03
Volume: 258
Issue: 3
Pages: 853-863
ISSN: 0033-8419 (ISSN-L)
1527-1315
DOI: 10.1148/radiol.10101284
OpenAlex: W2168463796
Cited by: 288
References: 53
Citations by year: 2026: 8 · 2025: 13 · 2024: 12 · 2023: 21 · 2022: 11 · 2021: 17 · 2020: 24 · 2019: 14 · 2018: 17 · 2017: 11 · 2016: 27 · 2015: 25 · 2014: 19 · 2013: 26 · 2012: 26
FWCI: 14.96
Type: journal article
Language: en
Open access: closed
Locations: Radiology (publishedVersion)
PubMed (publishedVersion)
Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, white matter injury, gray matter atrophy, amnestic mild cognitive impairment, diffusion tensor imaging, mean diffusivity, fractional anisotropy, axial and radial diffusivity, white matter tracts, corticospinal tract, fornix, corpus callosum, tract-based spatial statistics, voxel-based morphometry
MeSH terms: Aged, Alzheimer Disease, Atrophy, Cognition Disorders, Female, Humans, Male, Nerve Fibers, Myelinated, Neuropsychological Tests, Prospective Studies, Biomarkers, Case-Control Studies, Statistics, Nonparametric, Diffusion Magnetic Resonance Imaging

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White Matter Damage in Alzheimer Disease and Its Relationship to Gray Matter Atrophy

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