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CSF A?1-42 predicts cognitive impairment in de novo PD patients

Terrelonge, M; Marder, K; Weintraub, D; Alcalay, R
AAN: Washington, DC
Download Presentation: Terrelonge-AAN-2015.pdf
OBJECTIVE: To evaluate the relationship between baseline CSF protein A?1-42 levels and cognitive impairment (CI) at two-year follow-up among newly diagnosed Parkinson?s disease (PD) patients.

BACKGROUND: Low CSF A?1-42 has been associated with cognitive deterioration in advanced PD, but its impact in early PD is unknown.

DESIGN/METHODS: 215 PD patients in Parkinson?s Progression Markers Initiative were assessed in their newly diagnosed (mean disease duration 7.6 months), untreated state at baseline and followed for two years. CSF proteins were collected at baseline (A?1-42, T-tau, P-tau 181, and ?-synuclein). Participants were assigned as having CI if scores on two of six cognitive tests (Hopkins Verbal Learning Test-Revised immediate recall and recognition recall, Benton Judgment of Line Orientation, Semantic (animal) Fluency, Letter-Number Sequencing, and Symbol-Digit Modalities Test) were 1.5 standard deviations below the standardized mean based on published norms in healthy controls. Baseline CSF protein levels were compared between those with and without CI using a two-tailed t-test, and adjusted multivariable logistic regression analysis was used to determine the association between baseline CSF A?1-42 with CI at two-year follow-up.

RESULTS: 31 patients (14.4%) had CI at baseline; 15 of those patients continued to have CI at two years. 32 of the 184 patients without CI at baseline (17.4%) developed CI at two years. Participants with CI at two years had significantly lower mean baseline CSF A?1-42 levels than non-CI participants (323.4 vs. 369.1 pg/mL, p<0.01); no significant difference was seen for ?-synuclein, T-tau, or P-tau 181. In a regression model of all 215 patients adjusted for age, sex, education, PD duration, motor severity, depression, and baseline CI status, lower baseline A?1-42 levels were associated with higher odds of CI at two years. (OR[10-units]=1.05, 95%CI: 1.01-1.10, p=0.02).

CONCLUSIONS: A?1-42 is an independent predictor of CI at two years in patients with early PD.