The impact of common genetic variants in cognitive decline in the first seven years of Parkinson's disease: A longitudinal observational study

Abstract

Introduction: Cognitive impairment is a common feature of Parkinson's disease and is a significant determinant of patients' quality of life and dependence. The pattern and progression of cognitive symptoms vary greatly between individuals, and genetic biomarkers may help to predict the severity and trajectory of cognitive impairment in groups of patients.

Methods: The study included 171 patients from a longitudinal population-based incident Parkinson's disease study from South Western Norway. All participants were followed from the time of diagnosis for up to seven years, undertaking repeated batteries of clinical and neuropsychological tests, measuring global cognitive impairment, executive function, attention, verbal learning and memory, and visuospatial skills. We used linear mixed regression analyses to explore associations between the function in specific cognitive domains over time and common genetic variants in APOE, MAPT, COMT and BDNF.

Results: The COMT¹⁵⁸Val/Val allele wasassociatedwith faster decline in executive function (p = 0.028), verbal learning and memory (p = 0.029), and visuospatial skills (p = 0.027). The BDNF, MAPT and APOE genotypes were not significantly associated with longitudinal changes in individual cognitive domains, however carriers of the APOE-ε4 allele were shown to be at increased risk of mild cognitive impairment and dementia within the study period (OR3.03; p = 0.006).

Conclusions: This population-based study of newly diagnosed patients provides new evidence that COMTVal¹⁵⁸Met effects cognitive outcomes limited to discrete domains and APOE-ε4 status predicts a poor overall cognitive prognosis. Together, these data contribute to our understanding of the biology underlying the heterogeneity observed in the progression of PD.

Keywords: APOE; BDNF; COMT; Cognitive impairment; MAPT; Parkinson’s disease.