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Abstract
Objective: To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.
Methods: We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of Aβ42, Aβ40, and Aβ38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of Aβ42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.
Results: CSF levels of Aβ42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (−33%, p = 0.006) as well as ELISA (−36%, p < 0.001). No differences were observed for other markers. Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (≥85%), with hazard ratios of 9.9 (95% confidence interval 2.3–43.5, p = 0.002) for Aβ42ECL <376 pg/mL and 7.6 (2.2–26.4, p = 0.001) for Aβ42ELISA <443 pg/mL, after adjustment for baseline age and PD–mild cognitive impairment (MCI) status. Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia.
Conclusions: These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- AUC=
- area under the receiver operating characteristic curve;
- CI=
- confidence interval;
- ECL=
- electrochemiluminescence;
- LP=
- lumbar puncture;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- NPV=
- negative predictive value;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease dementia;
- PPV=
- positive predictive value;
- ROC=
- receiver operating characteristic
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 1758
Supplemental data at Neurology.org
- Received June 27, 2013.
- Accepted in final form January 16, 2014.
- © 2014 American Academy of Neurology
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