Damage to the cingulum contributes to Alzheimer’s disease pathophysiology by deafferentation mechanism
Open accessAbstract
This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimer's disease (AD). Thirty‐one patients with probable AD, 23 with amnestic mild cognitive impairment (a‐MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel‐based morphometry was used to assess regional GM atrophy in AD and a‐MCI patients. Diffusion tensor‐MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel‐by‐voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a‐MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro‐ and (to a lesser extent) macroscopic damage of patients' cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients' measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
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A well-replicated finding concerns microstructural changes in the posterior and parahippocampal cingulum associated with both MCI and AD.
“A well-replicated finding concerns microstructural changes in the posterior and parahippocampal cingulum associated with both MCI and AD (Bozzali et al., 2012; Choo et al., 2010; Metzler-Baddeley et al., 2012a; Remy et al., 2015; Wang et al., 2017; Zhang et al., 2007; Zhuang et al., 2012; 2013, for review see Chua et al., 2008; Yu et al., 2017).”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Bozzali et al., 2012
The Discussion and ‘WM Damage to the Cingulum Bundles’ results report altered diffusion measures in the cingulum in both AD and amnestic MCI, supporting the central association. The passages describe widespread or diffuse changes, but do not establish that both the posterior and parahippocampal segments are specifically affected in both groups; the reported parahippocampal gray-matter findings are distinct from changes in that cingulum segment. Page numbers are unavailable in our copy. (LLM, conf=0.78)
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- Authors
- Bozzali, M., Giulietti, G., Basile, B., Serra, L., Spanò, B., Perri, R., Giubilei, F., Marra, C., Caltagirone, C., & Cercignani, M.
- Affiliations
- Fondazione Santa Lucia (IT)
- Sapienza University of Rome (IT)
- Università Cattolica del Sacro Cuore (IT)
- University of Rome Tor Vergata (IT)
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2011-04-21
- Volume
- 33
- Issue
- 6
- Pages
- 1295-1308
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6870125
- OpenAlex
- W2115614582
- Cited by
- 107
- References
- 52
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 11 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 6
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Funders
- Ministero della Salute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- Alzheimer's disease, cingulum, deafferentation, gray matter atrophy, white matter injury, fractional anisotropy, mean diffusivity, posterior cingulate cortex, anterior cingulate cortex, episodic memory, amnestic mild cognitive impairment, cognitive impairment progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Fibers, Myelinated, Disease Progression, Nerve Fibers, Unmyelinated, Diffusion Tensor Imaging, Cognitive Dysfunction
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