Structural alterations of the brain evident on MRI 7 years before amyloid plaques in AD patients
New imaging data suggest that changes in the brain’s cortical thickness could precede the high levels of amyloid plaques associated with Alzheimer’s disease by up to seven years.
Published in Nature Neuroscience, the study details how researchers combined longitudinal MRI data with amyloid-beta (Aβ) PET imaging to identify subtle structural changes in the brains of individuals who went on to develop AD. The analysis found that people who eventually saw elevated Aβ plaques had thicker cortical regions and slower rates of cortical thinning compared with individuals who remained Aβ-negative.
Experts suggest their findings add to the growing body of evidence pointing to earlier structural alterations as clues that could signal the future development of AD, even before a high amyloid burden is evident.
“Studies on the temporal sequence of biomarker changes in the years before an AD diagnosis or expected onset of clinical symptoms suggest brain structural changes occur later than high levels of Aβ (that is, Aβ positivity), consistent with disease progression models of biomarker sequencing. However, as the most common MRI-based marker of neurodegeneration, studies typically focus on measures of hippocampus or global brain volumes and their temporality within the disease process," James M. Roe, with the department of radiology at Oslo University Hospital in Norway, and colleagues explained. "Whether wider brain structural changes may be evident in the years preceding high Aβ levels remains unknown, and few studies examine brain changes using MRIs acquired exclusively before Aβ positivity.”
The differences were detectable as early as seven years before participants were deemed to be Aβ-positive, suggesting structural brain changes may precede the key biomarkers currently used to diagnose AD. Some of the cortical thickness differences persisted after researchers accounted for quantitative amyloid levels, prompting the team to signal that at least some structural changes may occur independently of measurable amyloid accumulation. The timing of changes in cortical thickness also appeared to track with the progression of amyloid accumulation, providing additional evidence of a relationship between the structural and molecular imaging findings.
While the study does not establish whether cortical changes directly contribute to AD or represent an independent process that accompanies early pathology, the group indicated their findings warrant additional exploration of the possibility. The researchers said further studies are needed to determine how the structural changes relate to amyloid accumulation and other biomarkers over the course of disease.
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In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She began covering the medical imaging industry for Innovate Healthcare in 2021.