Neuroimaging-driven brain age estimation has introduced a robust (reliable and heritable) biomarker for detecting and monitoring neurodegenerative diseases. Here, we computed and compared brain age in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients using an advanced machine learning procedure involving T1-weighted MRI scans and gray matter (GM) and white matter (WM) models. Brain age estimation frameworks were built using 839 healthy individuals and then the brain estimated age difference (Brain-EAD: chronological age subtracted from brain estimated age) was assessed in a large sample of PD patients (n = 160) and AD patients (n = 129), respectively. The mean Brain-EADs for GM were +9.29 ± 6.43 years for AD patients versus +1.50 ± 6.03 years for PD patients. For WM, the mean Brain-EADs were +8.85 ± 6.62 years for AD patients versus +2.47 ± 5.85 years for PD patients. In addition, PD patients showed a significantly higher WM Brain-EAD than GM Brain-EAD. In a direct comparison between PD and AD patients, we observed significantly higher Brain-EAD values in AD patients for both GM and WM. A comparison of the Brain-EAD between PD and AD patients revealed that AD patients may have a significantly “older-appearing” brain than PD patients.
Table 1 Characteristics of subjects in this study.
Figure 1. The pipeline of the T1w MRI-driven brain age estimation framework used in this study.
Figure 2. Chronological age versus estimated brain age in the training set (n = 839) through 10-fold cross-validation strategy. (A) GM model. (B) WM model. The identity line is illustrated with a dashed black line (y = x).
Mean Brain-EAD [SD]
Table 2 Performance of the proposed brain age framework in the training set.
Figure 3. Comparison of Brain-EAD values between PD patients (blue spot) and AD patients (red spot) for the GM and WM models. The mean brain-EAD values of each group is illustrated with a solid black line. The reference line is illustrated with a dashed black line (y = 0).
Figure 4. GM and WM Brain-EAD distributions for PD, and AD individuals.
Figure 5. Chronological age versus estimated brain age among PD patients (blue spot, blue regression line) and AD patients (red spot, red regression line). (A) GM model. (B) WM model. The identity line is illustrated with a dashed black line (y = x).
Figure 6. Brain-EAD values versus chronological age among PD patients (blue spot, blue regression line) and AD patients (red spot, red regression line). (A) GM model. (B) WM model. The reference line is illustrated with a dashed black line (y = 0).
Table 3 Partial correlation (r) of GM Brain-EAD with adjustment for age and sex among AD patients (n = 129)
Figure 7. Partial correlations between Brain-EAD results and clinical parameters in the PD group. (A) MoCA, (B) MDS-UPDRS Part I, and (C) UPSIT - Total Score. Variables showing a significant correlation with Brain-EAD are shown.
Duration of disease
UPSIT - Total Score
MDS-UPDRS Part I
MDS-UPDRS Part I Patient Questionnaire
MDS-UPDRS Part II Patient Questionnaire
MDS-UPDRS Part III
Table 4 Partial correlation (r) of WM Brain-EAD values with clinical parameters among PD patients with adjustment for age and sex (n = 160).
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