Multimodal magnetic resonance imaging of brain asymmetries in Alzheimer’s disease: a systematic review

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by widespread cognitive decline, typically affecting functions that are intrinsically lateralized in the human brain, such as language and visuospatial processing. Identifying alterations in brain asymmetry therefore offers a principled framework for understanding selective vulnerability and network-level disruption in AD. In this review, we systematically synthesize evidence from multimodal magnetic resonance imaging studies examining hemispheric asymmetries across the clinical AD continuum, including subjective cognitive decline, mild cognitive impairment (MCI), and dementia. Three convergent patterns were indicated in the literature. Firstly, structural investigations suggest increased hippocampal asymmetries in AD, evident in both volumetric and shape measures. In parallel, connectivity-based analyses indicate a pronounced left-hemispheric vulnerability, characterized by decreased leftward or increased rightward asymmetry driven predominantly by degeneration of the left hemisphere. Importantly, distinct amygdala shape asymmetry profiles observed in MCI relative to healthy aging suggest sensitivity to early pathological changes and potential utility as a state-specific biomarker. Collectively, these findings position disrupted brain asymmetry as a systems-level hallmark of AD rather than a secondary epiphenomenon. This suggests that integrating asymmetry-informed metrics across imaging modalities may enhance early detection, refine disease staging, and improve sensitivity to longitudinal progression in AD.