Association between plasma phosphorylated tau-217 and cognition in Parkinson's disease

BackgroundIt is increasingly recognized that Alzheimers disease (AD) co-pathology contributes to dementia in PD, but its role in earlier stages of cognitive impairment remains uncertain. This study examined whether plasma phosphorylated Tau at threonine 217 (p-tau217), a biomarker of early AD-related pathology, is associated with cognitive impairment in PD. MethodsUsing cross-sectional data from 167 PD patients without dementia and 63 controls of the Quebec Parkinson Network registry we examined the association between plasma p-tau217 and three measures of cognitive impairment: performance on standard neuropsychological testing, and cognitive impairment as defined by a Montreal Cognitive Assessment (MoCA) score <26 and by self-report. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light chain (NfL) were also measured as non-specific markers of inflammation and neurodegeneration. ResultsNo significant difference in p-tau217 level was observed between groups; GFAP and NfL were higher in PD patients, but these differences did not survive multiple comparison correction (pFDR > 0.08). Among PD patients, higher p-tau217 was associated with worse visuospatial function (p=0.04) and greater self-reported cognitive impairment (p=0.03), but these associations did not survive multiple comparison correction (pFDR > 0.08). There was no association with cognitive impairment as defined by a MoCA <26. ConclusionPlasma p-tau217 was not clearly associated with early cognitive impairment suggesting that co-morbid AD pathology is not a major contributor to early cognitive changes in this sample of PD patients without dementia. Replication of these findings and longitudinal research is needed to determine whether p-tau217 can predict progression to dementia in PD.