Objective: To determine if the presence of APOEɛ4 allele (APOE4+) predicts longitudinal cognitive decline in Parkinson’s disease (PD) patients with low CSFAβ42

Background: Cognitive impairment in PD is common and disabling. Biomarkers that predict risk for cognitive decline are important as therapies that slow disease are likely to be more effective when implemented earlier. Studies suggest that in non-demented PD patients low CSFAβ42 increases risk for future cognitive decline. APOE4+ has also been shown to predict cognitive decline in PD. Studies from normal individuals with high CNS amyloid and APOE4+ show a higher rate of cognitive decline than either factor individually. We predicted that in non-demented PD patients with low CSF Aβ at baseline, APOE4+ will further increase risk for cognitive decline

Methods: Using the Parkinson Progression Markers Initiative database (downloaded 6/1/2016), we included all non-demented, de novo PD patients with low CSFAβ at baseline (defined as <310 ug/mL, N=61).  We then divided the cohort into APOE4+ (defined as at least one APOEɛ4 allele, N=22) or APOE4- (no APOEɛ4 allele, N=39). We considered 3 neuropsychological scores [Hopkins Verbal Learning Test-Revised (HVLT), Semantic Fluency Test (SFT), and Montreal Cognitive Assessment (MoCA)] and assessed scores at 4 timepoints (baseline, year 1, 2, and 3).  In PD patients with low CSFAβ at baseline, we determined the effect of APOE4+ on baseline scores as well as the annual rate of change using a linear mixed effects model adjusted for age, gender, and education

Results: For the MoCA, baseline scores were similar in both groups (APOE+ and APOE-); however the rate of decline was significantly faster in the APOE4+ group with an accelerated decline of 0.457 points annually (95%CI: 0.017-0.897, p=0.04). For the HVLT, baseline scores were similar in both groups; however, the rate of decline trended toward being faster in the APOE4+ group (p=0.13). For the SFT, baseline scores trended toward being lower in in the APOE4+ group compared to APOE4– (p=0.06); however, decline over time was similar in both groups

Conclusions: APOE4+ accelerates rate of cognitive decline in PD patients with low CSF Aβ42. Additionally, baseline scores on SFT were significantly lower at baseline. These results suggest that APOE4 may represent an independent clinically significant biomarker to identify PD patients at greater risk for cognitive decline

References: Mata, I. F., Leverenz, J. B., Weintraub, D. et al. (2014). APOE, MAPT, and SNCA Genes and Cognitive Performance in Parkinson Disease. JAMA Neurol. 2014;71(11):1405-1412. Mormino, E. C., Betensky, R. A., Hedden T., (2014). Amyloid and APOE4 interact to influence short-term decline in preclinical Alzhemier disease. Neurology. 2014;82(20):1760-7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apoe4-status-increases-rate-of-longitudinal-cognitive-decline-in-parkinson-disease-patients-with-low-csf-a%ce%b242/