Selnes, P;
Stav, AL;
Johansen, KK;
Bjornerud, A;
Coello, C;
Auning, E;
Kalheim, L;
... Fladby, T; + view all
(2017)
Impaired synaptic function is linked to cognition in Parkinson's disease.
Annals of Clinical and Translational Neurology
, 4
(10)
pp. 700-713.
10.1002/acn3.446.
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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, 18F‐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 Aβ, 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 Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.
| Type: | Article |
|---|---|
| Title: | Impaired synaptic function is linked to cognition in Parkinson's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/acn3.446 |
| Publisher version: | http://dx.doi.org/10.1002/acn3.446 |
| Language: | English |
| Additional information: | © 2017 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, CEREBROSPINAL-FLUID BIOMARKERS, ALZHEIMERS-DISEASE, ALPHA-SYNUCLEIN, AMYLOID-BETA, LEWY BODIES, IN-VIVO, NORWEGIAN PARKWEST, DEMENTIA, BRAIN, NEUROGRANIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10056833 |
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