Mind the gap – Interthalamic adhesions in prodromal and clinical Alzheimer’s disease

Background: The interthalamic adhesion (IA) is an anatomical bridge connecting the left and right thalamus. While prior studies have explored its prevalence and function in healthy populations, stroke, hydrocephalus, and schizophrenia, none have examined the IA in the context of Alzheimer’s disease (AD). This study aims to analyse the prevalence of the IA in the prodromal to clinical AD continuum and evaluate the association with AD cerebrospinal fluid (CSF) biomarkers and thalamic, hippocampal, and ventricular volumes.

Method: IA prevalence was assessed in 542 MRIs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including healthy controls (HC), early mild cognitive impairment (EMCI), late MCI (LMCI), and AD patients. Inter-rater reliability was assessed with Cohen’s Kappa, and a chi-squared test (χ2) examined rater differences. Binary and multinomial logistic regressions evaluated the effect of CSF biomarkers, volumes, and clinical data on IA prevalence and type.

Results: There were no significant differences in IA prevalence or variants across the four groups. The single IA was the most common type, while bilobar and double variants were less frequent. Post-hoc analysis, however, showed that AD CSF biomarker measures showed positive associations with the broad IA subtype in HC and EMCI.

Conclusion: The study found no overall differences in IA prevalence or its variants related to prodromal or clinical AD. Still, elevated Aβ42, p-Tau levels, and larger thalamic volume were linked to a higher likelihood of a broad IA. These findings suggest that the IA may be involved in prodromal AD pathophysiological processes.