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

Aurélie Bussy1, Raihaan Patel2, Olivier Parent1

  • 1Computational 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.

Neurobiology of Aging
|February 17, 2025
PubMed

Insights

Early Alzheimer's disease (AD) involves neural changes like myelin loss. Quantitative MRI (qMRI) reveals these changes are linked to lifestyle factors and genetic risk, even before cognitive decline.

Area of Science:

  • Neuroimaging
  • Neuropathology
  • Gerontology

Background:

  • Early Alzheimer's disease (AD) pathophysiology involves neural alterations, including myelin degeneration and inflammation-related iron accumulation.
  • Identifying reliable biomarkers for early AD detection is crucial for timely intervention.
  • Multi-modal neuroimaging approaches can capture complex pathological changes.

Purpose of the Study:

  • To identify multi-modal imaging signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in individuals across the AD spectrum.
  • To investigate the relationship between these neuroimaging markers and cognitive status, lifestyle factors, and genetic predisposition.
  • To assess the utility of qMRI metrics in detecting early pathological changes in AD.

Main Methods:

  • Recruited 158 participants across the AD spectrum: cognitively unimpaired, familial AD risk, mild cognitive impairment (MCI), and AD dementia.
  • Utilized MRI-derived atrophy measures and quantitative MRI (qMRI) to assess myelin and iron content.
  • Analyzed associations between neuroimaging findings, lifestyle factors (smoking, hypertension, hypercholesterolemia, anxiety), age, AD progression, and APOE-ɛ4 carrier status.

Main Results:

  • A distinct brain pattern was identified, characterized by decreased cortical thickness (indicating neuronal loss) and compromised hippocampal integrity due to reduced myelin.
  • This pattern significantly correlated with modifiable lifestyle factors including smoking, high blood pressure, high cholesterol, and anxiety.
  • Associations were also found with older age, AD progression, and APOE-ɛ4 carrier status.

Conclusions:

  • Quantitative MRI (qMRI) metrics serve as sensitive, non-invasive indicators of early neural alterations in Alzheimer's disease.
  • These qMRI markers are associated with both genetic risk (APOE-ɛ4) and modifiable lifestyle factors, even in preclinical stages.
  • qMRI offers a promising tool for early detection and monitoring of AD pathophysiology, highlighting the importance of addressing risk factors.
Keywords:
AgingAlzheimer’s diseaseIronMyelinQuantitative magnetic resonance imaging

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