Background: The longitudinal impact of APOE-ε4 on motor symptoms and cognitive decline in Parkinson's disease is unclear. Here we examine the effects of APOE-ε4 carrier status on motor symptoms, cognition and risk of Parkinson’s disease with dementia.
Methods: We evaluated data from the New Zealand Parkinson’s Progression Programme, a longitudinal study running over a 15 year period. We assessed the effect of APOE-ε4 carrier status in the Parkinson’s cohort (any ε4 carrier, n=109, non-ε4 carriers, n=254) on motor symptom severity (Unified Parkinson's disease rating scale, 1249 assessments), cognition (Montreal cognitive assessment, 1709 assessments) and rate of progression to Parkinson’s disease with dementia using Bayesian regression modelling. A Cox-proportional hazards regression estimated the dementia hazard-ratio associated with an APOEε-4 positive status since Parkinson’s disease diagnosis.
Results: APOE-ε4 carriers had poorer cognition scores and a greater probability of progressing to Parkinson’s disease with dementia (Hazard Ratio = 2.7 [1.7, 4.2]) than non-APOE-ε4 carriers. APOE-ε4 carriers converted to dementia a median of 5.7 years earlier than non-APOE-ε4 carriers. There was no evidence APOE-ε4 status was related to decline in motor symptom severity.
Conclusions: A modest proportion of our Parkinson’s sample had an APOE-ε4 allele. APOE-ε4 is predictive of future cognitive, but not motor symptom severity in Parkinson’s disease. APOE-ε4 also increases the risk of an earlier dementia diagnosis. APOE-ε4 may be an effective target for personalised therapeutic intervention to delay the onset of dementia in individuals with Parkinson’s disease carrying the deleterious allele.