Investigating baseline structural MRI differences in individuals who progress along the Alzheimer’s disease continuum and those who remain cognitively stable

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Saadat_Nazanin_PhD_2025.pdf (2.37 MB)

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2025

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Saadat, Nazanin

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Abstract

Early detection of neurodegenerative change is a critical priority in Alzheimer’s disease (AD) research. Structural brain alterations may emerge years before clinical symptoms become apparent, offering a potential window for identifying individuals at risk for cognitive decline. This dissertation investigates baseline structural brain differences in individuals who later progress along the AD continuum, with a particular emphasis on the transition from normal cognition (NC) to mild cognitive impairment (MCI). Study 1 presents a systematic review of whole-brain MRI studies comparing individuals who remained cognitively stable with those who progressed to MCI or AD. Whole-brain atrophy was the most consistent finding in NC-to-MCI converters, whereas medial temporal lobe atrophy was most robustly observed in MCI-to-AD progression. Study 2 offers a complementary review of region-of-interest (ROI) studies, highlighting a narrow anatomical and methodological focus within NC-to-MCI research. Most studies relied on hippocampal volumetry, with limited exploration of additional imaging modalities such as cortical thickness or white matter hyperintensity (WMH) volume. Study 3 addresses these gaps using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine baseline gray matter volume, cortical thickness, and WMH volume in NC individuals who later developed MCI. Only gray matter volume in the parahippocampal gyrus showed significant group differences. Collectively, these studies contribute to a more nuanced understanding of early structural brain differences and underscore the value of multimodal imaging approaches and greater methodological diversity in preclinical AD research.

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Alzheimer's disease (AD), Mild cognitive impairment (MCI), Structural MRI, Neuroimaging biomarkers, Conversion to MCI, Conversion to AD, Early detection

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https://hdl.handle.net/1828/22675

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