An increased rate of longitudinal cognitive decline is observed in Parkinson's disease patients with low CSF ASS42 and an APOE epsilon4 allele. Neurobiology of disease Shahid, M., Kim, J., Leaver, K., Hendershott, T., Zhu, D., Cholerton, B., Henderson, V. W., Tian, L., Poston, K. L. 2019


OBJECTIVE: Low concentrations of cerebrospinal fluid (CSF) amyloid-beta (Abeta-42) are associated with increased risk of cognitive decline in Parkinson's disease (PD). We sought to determine whether APOE genotype modifies the rate of cognitive decline in PD patients with low CSF Abeta-42 compared to patients with normal levels.METHODS: The Parkinson's Progression Markers Initiative is a longitudinal, ongoing study of de novo PD participants, which includes APOE genotyping, CSF Abeta-42 determinations, and neuropsychological assessments. We used linear mixed effects models in three PD groups (PD participants with low CSF Abeta at baseline, PD participants with normal CSF Abeta, and both groups combined). Having at least one copy of the APOE ?4 allele, time, and the interaction of APOE ?4 and time were predictor variables for cognitive change, adjusting for age, gender and education.RESULTS: 423 de novo PD participants were followed up to 5?years with annual cognitive assessments. 103 participants had low baseline CSF Abeta-42 (39 APOE epsilon4+, 64 APOE epsilon4-). Compared to participants with normal CSF Abeta-42, those with low CSF Abeta-42 declined faster on most cognitive tests. Within the low CSF Abeta-42 group, APOE epsilon4+ participants had faster rates of decline on the Montreal Cognitive Assessment (primary outcome; 0.57 points annual decline, p?=?.005; 5-year standardized change of 1.2) and the Symbol Digit Modalities Test (1.4 points annual decline, p?=?.002; 5-year standardized change of 0.72).DISCUSSION: PD patients with low CSF Abeta-42 and APOE epsilon4+ showed a higher rate of cognitive decline early in the disease. Tests of global cognition (Montreal Cognitive Assessment) and processing speed (Symbol Digit Modalities Test) were the most sensitive to early cognitive decline. Results suggest that CSF Abeta-42 and APOE epsilon4 might interact to promote early cognitive changes in PD patients.

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