Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

Affiliations

¹ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada. Electronic address: aureliee.bussy@gmail.com.
² Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
³ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁴ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁵ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁶ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University St, Montreal, QC H3A2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁷ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁸ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁹ Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University St, Montreal, QC H3A2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
¹⁰ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.

PMID: 39961166
DOI: 10.1016/j.neurobiolaging.2025.01.011

Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

Aurélie Bussy et al. Neurobiol Aging. 2025 May.

. 2025 May:149:1-18.

doi: 10.1016/j.neurobiolaging.2025.01.011. Epub 2025 Feb 7.

Authors

Affiliations

¹ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada. Electronic address: aureliee.bussy@gmail.com.
² Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
³ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁴ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁵ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁶ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University St, Montreal, QC H3A2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁷ Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁸ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
⁹ Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, 3801 University St, Montreal, QC H3A2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.
¹⁰ Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, 6875 Bd LaSalle CIC Building, Verdun, QC H4H 1R3, Canada; Douglas Mental Health University Institute, 6875 Bd LaSalle, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Room 302, Irving Ludmer Building, 1033 Pine Ave. W., Montreal, QC H3A 1A1, Canada; Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 Rue University Suite 316, Montreal, QC H3A 2B4, Canada; Department of Psychiatry, McGill University, Ludmer Research & Training Building, 1033 Pine Avenue West, Montreal, QC H3A 1A1, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 Rue University, Montreal, QC H3A 2B4, Canada.

PMID: 39961166
DOI: 10.1016/j.neurobiolaging.2025.01.011

Abstract

Neural alterations, including myelin degeneration and inflammation-related iron burden, may accompany early Alzheimer's disease (AD) pathophysiology. This study aims to identify multi-modal signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in a unique dataset of 158 participants across the AD spectrum, including those without cognitive impairment, at familial risk for AD, with mild cognitive impairment, and with AD dementia. Our results revealed a brain pattern with decreased cortical thickness, indicating increased neuronal death, and compromised hippocampal integrity due to reduced myelin content. This pattern was associated with lifestyle factors such as smoking, high blood pressure, high cholesterol, and anxiety, as well as older age, AD progression, and APOE-ɛ4 carrier status. These findings underscore the value of qMRI metrics as a non-invasive tool, offering sensitivity to lifestyle-related modifiable risk factors and medical history, even in preclinical stages of AD.

Keywords: Aging; Alzheimer’s disease; Iron; Myelin; Quantitative magnetic resonance imaging.

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Conflict of interest statement

Declaration of Competing Interest The authors have no conflicts of interest to disclose.

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Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

Affiliations

Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous