Advanced brain aging in Parkinson’s disease with cognitive impairment

Patients with Parkinson’s disease and cognitive impairment (PD-CI) deteriorate faster than those without cognitive impairment (PD-NCI), suggesting an underlying difference in the neurodegeneration process. We aimed to verify brain age differences in PD-CI and PD-NCI and their clinical significance. A total of 94 participants (PD-CI, n = 27; PD-NCI, n = 34; controls, n = 33) were recruited. Predicted age difference (PAD) based on gray matter (GM) and white matter (WM) features were estimated to represent the degree of brain aging. Patients with PD-CI showed greater GM-PAD (7.08 ± 6.64 years) and WM-PAD (8.82 ± 7.69 years) than those with PD-NCI (GM: 1.97 ± 7.13, P adjusted = 0.011; WM: 4.87 ± 7.88, P adjusted = 0.049) and controls (GM: -0.58 ± 7.04, P adjusted = 0.004; WM: 0.88 ± 7.45, P adjusted = 0.002) after adjusting demographic factors. In patients with PD, GM-PAD was negatively correlated with MMSE ( P adjusted = 0.011) and MoCA ( P adjusted = 0.013) and positively correlated with UPDRS Part II ( P adjusted = 0.036). WM-PAD was negatively correlated with logical memory of immediate and delayed recalls ( P adjusted = 0.003 and P adjusted < 0.001). Also, altered brain regions in PD-CI were identified and significantly correlated with brain age measures, implicating the neuroanatomical underpinning of neurodegeneration in PD-CI. Moreover, the brain age metrics can improve the classification between PD-CI and PD-NCI. The findings suggest that patients with PD-CI had advanced brain aging that was associated with poor cognitive functions. The identified neuroimaging features and brain age measures can serve as potential biomarkers of PD-CI.