Parkinson's disease: evolution of cognitive impairment and CSF Aβ 1-42 profiles in a prospective longitudinal study.

Objective To evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-beta (A beta), total-Tau and phosphorylated-Tau in Parkinson's disease (PD). Methods 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). Results Patients with PD with low CSF A beta(1-42) levels at baseline were more often cognitively impaired than patients with intermediate and high A beta(1-42) levels. Sixty-seven per cent of the patients with low A beta(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 A beta(1-42) levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF A beta(1-42) levels at baseline developed cognitive impairment more frequently and earlier during follow-up. Conclusion We conclude that in patients with sporadic PD, low levels of A beta(1-42) are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients.