Parkinson's disease: evolution of cognitive impairment and CSF Aβ_1-42 profiles in a prospective longitudinal study.

Abstract

To evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson's disease (PD). Prospective, longitudinal, observational study up to 10 years with follow-up every 2  years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men). Patients with PD with low CSF Aβ_1-42 levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ_1-42 levels. Sixty-seven per cent of the patients with low Aβ_1-42 levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ_1-42 levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ_1-42 levels at baseline developed cognitive impairment more frequently and earlier during follow-up. We conclude that in patients with sporadic PD, low levels of Aβ_1-42 are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients.