Inflammatory, degeneration and neuritic growth biomarkers predict cognitive decline and dementia in Parkinson’s disease

Abstract

AbstractBackgroundCognitive decline is common in Parkinson’s disease (PD) and has been associated with cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers such as Aβ1‐42, total tau and phosphorylated tau in addition to inflammatory proteins. VGF, a nerve growth factor, is a promising marker that has recently been implicated in cognitive decline in dementia with Lewy bodies and could potentially play a role in PD. The aim of this study is to assess a wide panel of CSF biomarkers reflecting different neuropathological processes to determine which best predict cognitive decline and conversion to dementia in PD.MethodWe included 174 PD patients from the Swedish BioFINDER study, who were followed for up to 10 years. At baseline, 47 CSF biomarkers were measured, including Aβ1‐42, Aβ42/40, total tau, phosphorylated tau, α‐synuclein as well as markers of neurodegeneration, vascular, inflammatory, synaptic and lysosomal dysfunction. Cox regression analyses were applied to identify biomarkers predicting dementia, adjusting for age, sex, education and disease duration. We then used linear mixed effects models to assess whether the significant biomarkers predicted longitudinal cognitive decline in MMSE, memory and semantic fluency, controlling for age, sex, education and disease duration.ResultOf the PD patients, 29% converted to dementia during follow‐up (4.9 ± 2.2 years). At baseline, converters were older (p<0.001) and had worse memory and semantic fluency tests (<0.008) compared with non‐converters. Levels of CSF Aβ1‐42, Aβ42/40, tau, Neurofilament light, Serum Amyloid A (SAA), Interleukin 7, Interferon‐gamma‐inducible Protein‐10 (IP‐10) and VGF (p<0.037) significantly predicted conversion to dementia in univariate models. When these biomarkers were included in a multivariable regression model, only higher tau (p<0.001), lower VFG (p<0.001) and higher SAA (p=0.028) independently predicted dementia. Further, CSF tau predicted cognitive decline in MMSE and semantic fluency (p<0.005), lower VGF predicted decline in memory (0.012) and SAA predicted decline in MMSE (p=0.011).ConclusionThese findings suggest that CSF tau, SAA and VGF are useful markers to predict conversion to dementia and cognitive decline in PD. VGF is emerging as an additional prognostic biomarker for cognitive decline in PD.