Structural MRI phenotyping in Alzheimer’s disease: Comparison of visual rating scales, volumetry, and cortical thickness in a Serbian single-centre cohort

Alzheimer's disease (AD) is characterized by a heterogeneous clinical course, and magnetic resonance imaging (MRI)-based phenotyping has increasingly been utilized to elucidate this variability. The literature recognizes four predominant MRI phenotypes: typical, hippocampal-sparing, limbic-predominant, and minimal-atrophy. However, the compatibility of various MRI phenotyping methods remains insufficiently defined. This study aimed to assess the concordance between MRI phenotyping methods within a Serbian cohort consisting of 40 subjects. Four MRI phenotyping approaches were employed: scale-based, adjusted scale-based, volume-based, and thickness-based. The scale-based method exhibited moderate agreement with the adjusted scale-based approach and high concordance with volumetric methods. In contrast, the relationship between scale- and thickness-based phenotyping was less clear. The lack of significant agreement with demographic variables, along with the observed differences across clinical dementia rating (CDR) domains, further underscored the clinical heterogeneity among phenotypes. Overall, these findings suggest that visual scale-based MRI phenotyping may serve as a practical approach in resource-limited clinical settings where advanced methods are unavailable. However, the results must be interpreted with caution and require validation in larger independent cohorts. Further research is necessary to clarify the relationship between scale- and thickness-based phenotyping across different disease stages and to investigate discrepancies in demographic, apolipoprotein E (APOE)-related, and clinical phenotype patterns in this Serbian sample compared to other populations.