Does Cognitive Performance Decline as a Function of Age at Onset in Parkinson’s Disease? The Role of Age at assessment, Education, and Clinical Severity

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Abstract Background: Parkinson’s disease (PD) may present with early-onset (EOPD) or late-onset (LOPD). Cognitive decline has been reported more frequently in LOPD, although findings remain inconsistent, partly due to insufficient control of confounding factors such as age at assessment, education, and disease severity. Aims: To evaluate the impact of age at assessment, age at onset, education, clinical severity, and emotional factors on cognitive performance in PD, and to compare cognitive outcomes between EOPD, LOPD, and healthy controls in a Mexican cohort. Methods: We analyzed 249 patients with PD and 102 healthy controls from the Mex-PD cohort. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Multiple linear regression models were applied to identify predictors of cognition. Because of collinearity among age-related variables, moderation analyses examined interactions between age at assessment, age at onset, diagnostic group, and disease severity. Nearest-neighbor matching was used for group comparisons. Results: Age at assessment was the strongest predictor of cognitive performance, followed by education and disease severity. Age at onset was not independently associated with cognition. Cognitive differences between EOPD and LOPD disappeared after controlling for age at assessment. Disease severity significantly affected cognition from 59 years of age onward. In matched samples, both PD groups showed lower global cognition than controls, with delayed recall being the most affected domain. Conclusions: Cognitive decline in PD is mainly driven by aging and its interaction with disease severity rather than by age at onset. Education and cognitive reserve appear to exert protective effects.

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