Regional gyrification alterations and metabolic correlates in biologically defined Alzheimer's disease using a multimodal approach

: BackgroundSurface-based morphometry (SBM) metrics, such as the gyrification index (GI), have emerged as biomarkers for detecting early, subtle alterations in Alzheimer's disease (AD).ObjectiveWe investigated GI differences between biologically defined AD patients (based on cerebrospinal fluid (CSF)/positron emission tomography (PET) biomarkers), and participants with non-AD cognitive impairment. We further explored correlations between GI, regional metabolism (FDG-PET), cortical thickness (MRI), and cognitive performance using the Montreal Cognitive Assessment (MoCA).MethodsT1-weighted MRI and FDG-PET scans from 36 AD and 15 non-AD participants were retrospectively analyzed. GI was computed using both SPM-based whole-brain and ROI-atlas based analyses. FDG-PET was available for 27 AD and 13 non-AD participants and SUVRs were extracted from standard ROIs. Cognitive performance was measured via the MoCA.ResultsGI and metabolic uptake were reduced in the insula, while GI was increased in the entorhinal/parahippocampal cortex for AD participants. Metabolic uptake was also lower in the insula in AD. Insular GI correlated positively with metabolism (SUVR; R = 0.370, p = 0.021), cortical thickness (R = 0.510, p = 0.001), and MoCA scores (R = 0.554, p = 0.004). Parahippocampal GI was inversely associated with cortical thickness (R = -0.340, p = 0.034). No significant correlations were observed with CSF biomarkers.ConclusionsOur findings demonstrate region-specific GI alterations in AD, particularly in the insula and entorhinal cortex. The novel correlation between GI and metabolism suggests disease-related mechanisms linking cortical folding to synaptic dysfunction. These results highlight GI as a valuable early biomarker for AD with potential diagnostic and therapeutic implications.