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

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Abstract

Low CSF β-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson’s disease; data from a single cohort suggest β-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 β-amyloid 1-42, α-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 β-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for α-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 β-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 β-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson’s disease.

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Acknowledgments

PPMI is sponsored by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer, and UCB.

Authors’ Contributions

For the research project, MT, KM, and RA were responsible for the conception. MT and RA were in charge of the organization and execution. During the statistical analysis, all authors contributed to the design while the execution was done by MT. All authors were responsible for the review and critique. For the manuscript preparation, writing of the first draft was assigned to MT and RA while the review and critique was done by KM and DW.

Financial Disclosures

Dr. Marder reports grants from NIH [#NS036630 (PI), 1UL1 RR024156-01(Director PCIR), PO412196- G (Co-I), and PO412196-G (Co-I)], grants from steering committee for U01NS052592, grants from Parkinson disease Foundation, and grants from MJ Fox Foundation and research funds from Teva Pharmaceuticals outside the submitted work. Dr. Weintraub received research funding from the Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health, Novartis Pharmaceuticals, Department of Veterans Affairs, and Alzheimer’s Disease Cooperative Study; honoraria from Teva Pharmaceuticals, Lundbeck Inc., Pfizer, Avanir Pharmaceuticals, Merck & Co., UCB, Bristol-Myers Squibb Company, Novartis Pharmaceuticals, Eli Lilly and Company, Clintrex LLC, Theravance, Medivation, CHDI Foundation, and Alzheimer’s Disease Cooperative Study; license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS; and fees for testifying in court case related to impulse controls disorders in Parkinson’s disease (March 2013). Dr. Alcalay is supported by the Parkinson’s Disease Foundation, the National Institutes of Health (K02NS080915, NS036630, and UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156), and the Brookdale Foundation. He consulted for Genzyme/Sanofi and Prophase.

Funding Sources

No funding sources required for this study. Data support provided by the Michael J Fox Foundation Parkinson’s Progression Markers Initiative (PPMI) study.

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Authors and Affiliations

  1. Department of Neurology, Columbia University, 710 W 168th St, New York, NY, 10032, USA

    Mark Terrelonge Jr., Karen S. Marder & Roy N. Alcalay

  2. Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Daniel Weintraub

  3. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA

    Daniel Weintraub

Authors
  1. Mark Terrelonge Jr.
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  2. Karen S. Marder
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  3. Daniel Weintraub
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  4. Roy N. Alcalay
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Correspondence to Roy N. Alcalay.

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Terrelonge, M., Marder, K.S., Weintraub, D. et al. CSF β-Amyloid 1-42 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease. J Mol Neurosci 58, 88–92 (2016). https://doi.org/10.1007/s12031-015-0647-x

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  • DOI: https://doi.org/10.1007/s12031-015-0647-x

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