CSF amyloid {beta} 1-42 predicts cognitive decline in Parkinson disease

Abstract

Objective: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease.

Methods: A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid β 1-42 (Aβ(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time.

Results: Lower baseline CSF Aβ(1-42) was associated with more rapid cognitive decline. Subjects with CSF Aβ(1-42) levels ≤192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline.

Conclusions: Reduced CSF Aβ(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD.

Figure 1 Change over time in mean Dementia Rating Scale (version 2) (DRS-2) total score Change over time of the DRS-2 for subjects with CSF Aβ_1-42 levels above 192 pg/mL (solid line) compared to those with baseline Aβ_1-42 at or below 192 pg/mL (dashed line). Data shown are the mean predicted DRS-2 scores (±1 SE) based on output from a mixed linear model, adjusted for age, Hoehn & Yahr stage, and disease duration.