Global and regional brain-age gaps in primary trigeminal neuralgia: a cross-sectional structural MRI study of 133 anatomical structures

Abstract

Primary trigeminal neuralgia (TN) is a severe craniofacial neuropathic pain disorder. Quantitative magnetic resonance imaging (MRI) studies suggest that TN-related alterations may extend beyond the trigeminal pathways. The brain-age gap (BAG) is MRI-predicted brain age minus chronological age. Previous studies have found higher global BAG in TN, but global measures cannot identify the regions contributing to this difference. This cross-sectional secondary analysis included 87 patients with primary TN and 46 healthy controls. T1-weighted MRI scans were processed using the pretrained BrainStructureAges pipeline on the volBrain platform to estimate global predicted brain age and regional brain structure ages for 133 anatomical structures. The primary model adjusted for age, sex, and intracranial volume; a prespecified sensitivity model additionally adjusted for five image-quality metrics. Regional analyses controlled the false discovery rate (FDR). Secondary and exploratory analyses examined hemispheric asymmetry, pain laterality, and clinical associations. After adjustment for age, sex, and intracranial volume, global BAG was 3.05 years higher in the TN group than in controls (95% confidence interval [CI], 1.01–5.08; p = 0.004). Additional adjustment for the five image-quality metrics reduced this difference to 2.14 years (95% CI, 0.05–4.23; p = 0.045). In the primary model, 100 of 133 structures showed higher regional BAG in the TN group after FDR correction. After image-quality adjustment, regional BAG differences remained significant in 14 structures and ranged from 3.52 to 5.19 years, mainly within the frontopolar–orbitofrontal, frontal opercular–insular, and temporal polar–superior temporal clusters. No significant differences were found in the hemispheric asymmetry analysis or the direct comparison of the right- and left-sided pain subgroups. Regional asymmetry also did not vary significantly with pain side. None of the prespecified clinical associations with global BAG was significant after FDR correction. Patients with primary TN had a higher global BAG accompanied by regional BAG differences concentrated in selected frontal, opercular, insular, and temporal structures. Within the brain-age framework, the higher global BAG suggests an overall older-appearing structural MRI pattern, which can be described as apparent brain aging at the whole-brain level. Not applicable.