Cerebellar and frontal lobe alterations in pulmonary hypertension implicate an inflammatory lung vascular/brain axis.

In UK Biobank patients with pulmonary hypertension (N = 248), reduced cerebellar white matter volume, thinner frontal gyri, and weaker cerebellar–frontal connectivity are linked to worse executive function and processing speed.

• Why it matters: The vascular–neurocognitive relationship in pulmonary hypertension is unclear, despite shared inflammation with neurodegenerative disorders and recognized cognitive impairment in PH.
• What they did: Structural and functional MRI from UK Biobank, plus a prospective validation cohort, were integrated with Olink proteomics and targeted genomics, linking inflammatory plasma proteins and the NCOA7 SNP rs11154337 to cognitive deficits.
• The result: PH cerebellum showed increased microglial activation and white matter derangement, and in PH mice Ncoa7 deficiency worsened cerebellar inflammation and atrophy, implicating Ncoa7-dependent lysosomal and inflammatory mechanisms.

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