Nucleus Basalis of Meynert degeneration predicts cognitive decline in Corticobasal Syndrome

BACKGROUND:Cognitive changes are common in corticobasal syndrome (CBS) and significantly impact quality of life and caregiver burden. However, there is a scarcity of studies investigating the neural substrates of cognitive changes in CBS, and currently, reliable predictors of cognitive impairment are lacking. The nucleus basalis of Meynert (NbM), which serves as the primary source of cortical cholinergic innervation, has been functionally associated with cognition. This study aimed to explore whether patients with CBS exhibit reduced NbM volumes compared to healthy controls and whether NbM degeneration can serve as a predictor of cognitive impairment in CBS patients. METHODS: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 using 3 Tesla T1-weighted images obtained from the 4-Repeat Tauopathy Neuroimaging Initiative. RESULTS: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). DISCUSSION:Our findings suggest that NbM atrophy might represent a promising non-invasive in vivo marker of cognitive decline in CBS and provide new insights into the neural mechanisms underlying cognitive impairment in CBS.