Cognitive reserve and β-amyloid pathology in Parkinson disease

Introduction: Dementia in Parkinson disease (PD) is associated with abnormal accumulation of proteins, including β-amyloid, in cortical regions. High cognitive reserve capacity may protect cognition from β-amyloid and delay the onset of dementia. We tested the cognitive reserve theory in PD by determining whether educational attainment, a proxy for cognitive reserve, modifies the correlation between cortical β-amyloid accumulation and cognitive impairment. Methods: PD participants (N=155) underwent MRI to quantify brain volume and [¹¹C] PiB PET imaging to quantify fibrillar β-amyloid deposition. Mean cortical binding potentials (MCBP) were calculated for each participant, with higher scores indicating more fibrillar β-amyloid. Global cognitive function was assessed using the Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Multiple linear regression analysis was used to determine whether education modified the relationship between MCBP and cognitive function after controlling for brain volume. Results: MCBP interacted with educational attainment to predict scores on each of the cognitive outcome measures (ps≤0.02). Post-hoc analysis revealed that the effect of MCBP on cognitive function changed once the level of education reached 16 years. For participants with less than16 years of education (n=68), higher MCBP correlated with worse cognitive function, with MCBP accounting for 8-30% of the variance in MMSE and CDR scores (ps≤0.02). For participants with at least 16 years of education (n=87), MCBP did not correlate with MMSE or CDR scores (R²s<0.02, ps≥0.17). Conclusion: These findings provide support for the cognitive reserve theory in PD and suggest that education may protect PD patients' cognition against cortical β-amyloid pathology.