CSF β-Amyloid 1-42 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease

Low CSF beta-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson's disease; data from a single cohort suggest beta-amyloid 1-42 may be an early marker of cognitive impairment. Newly diagnosed Parkinson's participants (mean duration, 6.9 months) in the Parkinson's Progression Markers Initiative (n = 341) were assessed at baseline (untreated state) and followed for 2 years. CSF beta-amyloid 1-42, alpha-synuclein, total tau, and tau phosphorylated at threonine 181 were collected at baseline. Participants were classified as having cognitive impairment (CI) if scores on two of six cognitive tests were 1.5 standard deviations below the standardized mean based on published norms in healthy controls. Multivariable regression analyses were used to determine the association between baseline CSF markers with cognitive impairment, defined by neuropsychological testing performance at 2-year follow-up. Fifty-five participants (16.1 %) had CI at baseline and were not included in further analyses. Thirty-seven of the 286 participants without CI at baseline (12.9 %) developed CI at 2 years. Participants with CI at 2 years had significantly lower mean baseline CSF beta-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for alpha-synuclein, T-tau, or P-tau 181. In a regression model of 286 participants without baseline CI adjusted for age, gender, disease duration, education, motor severity, and depression status, lower baseline beta-amyloid 1-42 levels were associated with higher odds of CI at 2 years. (OR10pg/mL = 1.04, 95 % CI 1.01-1.08, p < 0.05). CSF beta-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson's disease.