Cerebellar and cerebral frontal lobe alterations in pulmonary hypertension: Evidence of an inflammatory lung vascular-brain axis [Spatial Transcriptomics]

Cognitive impairments have been reported in pulmonary hypertension (PH), a disease traditionally viewed as limited to the heart and lungs. Given that inflammation is a shared feature of PH and neurodegenerative diseases, we investigated its role in driving brain and cognitive deficits in PH.

Using structural and functional MRI data from UK Biobank (N=248 PH; N=11,656 controls) and a prospective validation cohort (N=10/group), we identified reduced cerebellar white matter volume, thinner frontal gyri, and weakened cerebellar-frontal connectivity in PH patients but not in other heart or lung diseases. These changes were accompanied by worsened executive function and processing speed. By unbiased Olink proteomic analysis and targeted genomic study, inflammatory plasma proteins and a PH-associated NCOA7 single nucleotide polymorphism (SNP) were associated with these deficits.