1 research outputs found
Impaired synaptic function is linked to cognition in Parkinson's disease
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 amyloidâβ species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloidâβ release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloidâβ, and presynaptic deposits of Îąâsynuclein. We expect a correlation between hypometabolism, CSF amyloidâβ, and the synapse relatedâmarkers CSF neurogranin and Îąâsynuclein.
METHODS:
Thirty patients with mildâtoâmoderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18FâfludeoxyglucoseâPET, and a neuropsychological test battery (repeated for the patients after 2 years).
RESULTS:
All subjects had CSF amyloidâβ 1â42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, Îąâsynuclein, and neurogranin. All PET CSF biomarkerâbased cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mildâtoâmoderate Parkinson's disease compared to controls, correlated with amyloidâβ and Îąâsynuclein, 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, Îąâsynuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and Îąâsynuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease