Cholinergic basal forebrain atrophy and cortical alterations in Parkinson's disease with apathy

Emerging evidences support the contribution of cholinergic deficiency to apathy in Parkinson's disease (PD). We aimed to ascertain the role of structural alterations of cholinergic basal forebrain (BF) and its innervated cortical regions in the pathogenesis of apathy in PD.

Twenty-one PD patients with apathy (PD-A), 28 without apathy (PD-NA), and 20 healthy controls (HCs) were recruited in this study. Changes in subregional volumes of the BF were compared. Cortical thickness and local gyrification index (LGI) analysis were adopted to reveal the concomitant cortical alterations. The correlation with the severity of apathy and the diagnostic capacity were also assessed.

Compared to PD-NA and HCs groups, PD-A group showed excessively nucleus basalis of Meynert (NBM/Ch4) atrophy (p < 0.05 after Bonferroni correction), accompanied by cortical thinning and hypergyrification of the right entorhinal cortex (p < 0.001 after Bonferroni correction). Furthermore, regression analysis showing that the Ch4 volume was negatively associated with the severity of apathy in PD-A group (β = -23.198, T = -1.063, p = 0.039). All the above significant neuroimaging alterations showed good performance in identifying apathetic patients (p < 0.001).

Our findings highlighted that BF cholinergic degeneration driven by Ch4 atrophy may be involved in the pathogenesis of apathy in PD patients without dementia or depression.