Cognitive changes are common in CBS and affect quality of life and carer burden considerably. Studies investigating the neural substrates of cognitive changes in CBS remain sparse and no reliable predictors of cognitive impairment exist at the moment. The NbM is the primary source of cortical cholinergic innervation and has been functionally associated with cognition.

In this study, we investigated in vivo volumetric changes of the NbM, between 38 patients with CBS and 64 healthy controls. Next, we assessed whether baseline gray matter degeneration of the NbM evaluated at baseline could predict cognitive impairment during a 12-month follow-up period in CBS patients. All volumetric analyses were performed on using 3 Tesla T1-weighted images obtained from the 4-Repeat Tauopathy Neuroimaging Initiative.

We demonstrated that patients with CBS displayed significantly lower NbM volumes compared to controls (p < 0.001). Structural damage of the NbM also predicted the development of cognitive impairment in patients with CBS as assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes (p < 0.001) and Mini-Mental State Examination (p=0.035).

Our findings suggest that NbM atrophy might represent a promising non-invasive in vivo marker of cognitive progression in CBS and can guide the exploration of medications targeting the cholinergic system.