Impaired synaptic function is linked to cognition in Parkinson's disease. Issue 10 (31st August 2017)

• Record Type: Journal Article
• Authors: Selnes, Per; Stav, Ane Løvli; Johansen, Krisztina K.; Bjørnerud, Atle; Coello, Christopher; Auning, Eirik; Kalheim, Lisa; Almdahl, Ina Selseth; Hessen, Erik; Zetterberg, Henrik; Blennow, Kaj; Aarsland, Dag; Fladby, Tormod
• Is Part Of: Annals of clinical and translational neurology. Volume 4:Issue 10(2017)
• Page Start: 700
• Page End: 713
• Publication Date: 2017-08-31
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.446
• Languages: English
• ISSNs: 2328-9503

Abstract

Abstract: Objective: Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐ β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐ β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐ β, and presynaptic deposits of α ‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐ β, and the synapse related‐markers CSF neurogranin and α ‐synuclein. Methods: Thirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18 F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years). Results: All subjects had CSF amyloid‐ β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF A β, α ‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐ β and α ‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group. Interpretation: CSF A β, α ‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to A β and α ‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.